Publications by authors named "Zhenhan Deng"

46 Publications

Intra-articular Injection of Bevacizumab Enhances Bone Marrow Stimulation-Mediated Cartilage Repair in a Rabbit Osteochondral Defect Model.

Am J Sports Med 2021 May 12:3635465211005102. Epub 2021 May 12.

Center for Regenerative Sports Medicine at the Steadman Philippon Research Institute, Vail, Colorado, USA; Department of Orthopaedic Surgery, McGovern Medical School, University of Texas Health Science Center, Houston, Texas, USA.

Background: Bone marrow stimulation (BMS) via microfracture historically has been a first-line treatment for articular cartilage lesions. However, BMS has become less favorable because of resulting fibrocartilage formation. Previous studies have shown that angiogenesis blockade promotes cartilage repair. Bevacizumab is a Food and Drug Administration-approved medication used clinically to prevent angiogenesis.

Hypothesis: The intra-articular injection of bevacizumab would prevent angiogenesis after BMS and lead to improved cartilage repair with more hyaline-like cartilage.

Study Design: Controlled laboratory study.

Methods: The dose of bevacizumab was first optimized in a rabbit osteochondral defect model with BMS. Then, 48 rabbits (n = 8/group/time point) were divided into 3 groups: osteochondral defect (defect), osteochondral defect + BMS (BMS group), and osteochondral defect + BMS + bevacizumab intra-articular injection (bevacizumab group). Rabbits were sacrificed at either 6 or 12 weeks after surgery. Three-dimensional (3D) micro-computed tomography (microCT), macroscope score, modified O'Driscoll histology scores, collagen type 2, Herovici staining, and hematoxylin and eosin staining were performed. Angiogenesis markers were also evaluated.

Results: The intra-articular dose of 12.5 mg/0.5 mL bevacizumab was found to be effective without deleteriously affecting the subchondral bone. Intra-articular injection of bevacizumab resulted in significantly improved cartilage repair for the bevacizumab group compared with the BMS or the defect group based on 3D microCT, the macroscope score (both < .05), the modified O'Driscoll histology score ( = .0034 and .019 vs defect and BMS groups, respectively), collagen type 2, Herovici staining, and hematoxylin and eosin staining at 6 weeks. Cartilage in the bevacizumab group had significantly more hyaline cartilage than did that in other groups. At 12 weeks, the cartilage layer regenerated in all groups; however, the bevacizumab group showed more hyaline-like morphology, as demonstrated by microCT, histology scores ( < .001 and .0225 vs defect and BMS groups, respectively), histology, and immunohistochemistry. The bevacizumab injection did not significantly change mRNA expressions of smooth muscle actin, vascular endothelial growth factor, or hypoxia-inducible factor-1 alpha.

Conclusion: Intra-articular injection of bevacizumab significantly enhanced the quality and quantity of hyaline-like cartilage after BMS in a rabbit model. Future large-animal and human studies are necessary to evaluate the clinical effect of this therapy, which may lead to improved BMS outcomes and thus the durability of the regenerated cartilage.

Clinical Relevance: The use of bevacizumab may be an important clinical adjunct to improve BMS-mediated cartilage repair.
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http://dx.doi.org/10.1177/03635465211005102DOI Listing
May 2021

Protective Effect of SIRT1 Activator on the Knee With Osteoarthritis.

Front Physiol 2021 13;12:661852. Epub 2021 Apr 13.

Department of Sports Medicine, The First Affiliated Hospital of Shenzhen University, Shenzhen Second People's Hospital, Shenzhen, China.

Osteoarthritis (OA), one of the most common chronic musculoskeletal disorders, is deemed to be correlated with aging. The SIRT1 activator, resveratrol, acts as a crucial regulator of aging and may have a potential therapeutic effect on OA. Rabbit OA models were established through destabilized medial meniscus surgery. A total of 40 healthy male New Zealand rabbits were divided into five groups: control group (sham operation), OA group, as well as low dose (LD), middle dose (MD), and high dose (HD) resveratrol-treated OA groups. 6 weeks after operation, 0.8 ml of normal saline was injected into the knee joints every other day in the control and OA groups, and 0.8 ml of 5, 10, and 15 μmol/L resveratrol was injected into the knee joints every other day in the LD, MD, and HD group, respectively. The rabbits were sacrificed 2 weeks after medication, and the articular cartilage of the knee joint was collected for Micro-CT, histology and Western blot analysis. Obvious articular cartilage lesion and joint space narrowing were detected in the OA group. Compared with the OA group, less osteoarthritic changes were observed in the MD and HD groups. The MD and HD groups had significantly lower bone volume fraction, trabecular number and Mankin scores than the LD and OA groups ( < 0.05). No significant difference was found between the OA and LD groups ( > 0.05). The expressions of SIRT1 and p53 detected by western blot were consistent with the aforementioned findings. Therefore, resveratrol can activate the SIRT1 gene to play a protective role in the OA process by inhibiting chondrocyte apoptosis, trabecular bone number increasing of the subchondral bone, as well as elevation of bone density. It demonstrated the importance of SIRT1 in maintaining articular cartilage health and provided a promising therapeutic intervention in the treatment of OA.
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http://dx.doi.org/10.3389/fphys.2021.661852DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8076744PMC
April 2021

Src Homology 2 Domain-Containing Protein Tyrosine Phosphatase Promotes Inflammation and Accelerates Osteoarthritis by Activating β-Catenin.

Front Cell Dev Biol 2021 9;9:646386. Epub 2021 Apr 9.

Department of Orthopedics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Osteoarthritis (OA) is a chronic articular disease characterized by cartilage degradation, subchondral bone remodeling and osteophyte formation. Src homology 2 domain-containing protein tyrosine phosphatase (SHP2) has not been fully investigated in the pathogenesis of OA. In this study, we found that SHP2 expression was significantly increased after interleukin-1β (IL-1β) treatment in primary mouse chondrocytes. Inhibition of SHP2 using siRNA reduced MMP3, MMP13 levels, but increased AGGRECAN, COL2A1, SOX9 expression . On the contrary, overexpression of SHP2 exerted the opposite results and promoted cartilage degradation. Mechanistically, SHP2 activated Wnt/β-catenin signaling possibly through directly binding to β-catenin. SHP2 also induced inflammation through activating Mitogen-activated protein kinase (MAPK) and nuclear factor κB (NF-κB) pathways. Our studies showed that SHP2 knockdown effectively delayed cartilage destruction and reduced osteophyte formation in the mouse model of OA induced by destabilization of the medial meniscus (DMM). Altogether, our study identifies that SHP2 is a novel and potential therapeutic target of OA.
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http://dx.doi.org/10.3389/fcell.2021.646386DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8063055PMC
April 2021

[Radiographic study of effect of lateral placement of bone graft on shoulder joint degeneration after modified arthroscopic Latarjet surgery with elastic fixation].

Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi 2021 Apr;35(4):414-419

Department of Sports Medicine, the First Affiliated Hospital of Shenzhen University (Shenzhen Second People's Hospital), Shenzhen Guangdong, 518000, P.R.China.

Objective: To investigate the mid-term effect of lateral placement of bone graft on shoulder joint degeneration after modified arthroscopic Latarjet surgery with elastic fixation for recurrent anterior shoulder dislocation with an anterior glenoid bone defect.

Methods: According to the inclusion and exclusion criteria, 18 patients with recurrent anterior shoulder dislocation and anterior glenoid bone defect who received the modified arthroscopic Latarjet surgery with elastic fixation between January 2015 and November 2016 were enrolled in this study. There were 12 males and 6 females with an average age of 26.2 years (range, 19-37 years). The number of shoulder dislocation ranged from 4 to 30 times (mean, 8.8 times). The disease duration was 8-49 months (mean, 23.8 months). The mean anterior glenoid bone defect was 25.2% of the glenoid surface (range, 20%-29%). The mean preoperative Instability Severity Index Score (ISIS) was 7.6 (range, 7-10). According to Samilson-Prieto classification, the shoulder joint degeneration was rated as grade 0 in 13 cases, grade Ⅰ in 3 cases, and grade Ⅱ in 2 cases. Before and after operation, the visual analogue scale (VAS) score, American Society of Shoulder and Elbow Surgery (ASES) score, Walch-Duplay score, Rowe score, and shoulder mobility were used to evaluate the effectiveness. Imaging examination was performed to observe the shoulder joint degeneration, the position of the bone graft, and the postoperative shaping of the scapular glenoid.

Results: All patients were followed up 55-62 months, with an average of 59.6 months. There was no neurovascular injuries, infections, fixation-related and bone graft-related complications. No re-dislocation and revision occurred. All patients returned to normal life, 17 of whom returned to sport. The VAS score was significantly decreased and ASES, Walch-Duplay, and Rowe scores were significantly improved at last follow-up ( <0.05). No significant difference was found in range of motion of forward flexion, abduction, lateral rotation at 90° abduction, internal rotation at 90° abduction, or lateral rotation at 0° between pre- and post-operation ( >0.05). Three-dimensional CT showed that the centers of all bone grafts were between 3∶30 and 4∶30 (right shoulder) or between 7∶40 and 8∶20 (left shoulder) and no bone grafts were positioned superiorly or inferiorly in the glenoid En-face view. All bone grafts were positioned lateral to the scapular glenoid with an average distance of 3.5 mm (range, 2.3-4.6 mm) in cross-sectional imaging by CT. Compared with the preoperative Samilson-Prieto classification results, all cases showed no progression of shoulder joint degeneration at 36, 48 months and last follow-up. All bone grafts remodeled to a steady state within 24 months after operation. The bone graft and glenoid finally remodeled analogous to the shape of the intact glenoid in the En-face view and became flush with the glenoid rim, remodeling to a curved shape congruent to the humeral head in cross-sectional imaging by CT. The shape of the remodeled glenoid at last follow-up was not significantly different from that at 24 months after operation.

Conclusion: The lateral placement of the bone graft during modified arthroscopic Latarjet surgery with elastic fixation do not accelerate the imaging changes of shoulder joint degeneration.
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http://dx.doi.org/10.7507/1002-1892.202011089DOI Listing
April 2021

Effects of earthworm extract on the lipid profile and fatty liver induced by a high-fat diet in guinea pigs.

Ann Transl Med 2021 Feb;9(4):292

Department of Orthopaedics, Xiangya Hospital, Central South University, Changsha, China.

Background: Non-alcoholic fatty liver disease (NAFLD), characterized by the accumulation of excess fat in the liver in people who consume little or no alcohol, is becoming increasingly common around the world, especially in developed countries. Extracts from earthworms have been used as alternative therapies for a variety of diseases but not in NAFLD. Therefore, the aim of this study was to investigate the effect of earthworm extract (EE) on diet-induced fatty liver disease in guinea pigs.

Methods: EE was extracted, and the effect of EE on the lipid levels and liver damage in guinea pigs fed a high-fat diet (HFD) was assessed. Thirty male guinea pigs at 3 weeks of age were allocated equally to five groups, namely, chow diet, HFD, and HFD with different dosages (0.3, 1.4 and 6.8 µg per kg bodyweight per day) of EE for 4 weeks, and their body weight was monitored throughout the experiment. Liver tissues were examined for gross morphology and histology. Serum levels of total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), alanine transaminase (ALT) and aspartate aminotransferase (AST) were determined using an autoanalyser.

Results: HFD induced NAFLD in guinea pigs. HFD-fed guinea pigs that received EE treatment showed milder increases in the serum levels of TC, TG and LDL-C, as well as in the body weight growth rate, compared to the HFD group without EE supplementation. EE intervention reduced the number of lipid-containing hepatocytes, hepatocellular ballooning and sinusoidal distortion in the liver in HFD-fed animals. ALT in serum was significantly elevated by HFD. No statistically significant difference in ALT levels was found between the chow diet group and the HFD group with EE treatment.

Conclusions: This study demonstrates that the administration of EE suppressed the induction of serum TC, TG and LDL-C in response to HFD. EE also reduced liver damage in HFD-fed guinea pigs. These findings suggest that EE has alleviating effects on dyslipidaemia and liver damage associated with NAFLD.
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http://dx.doi.org/10.21037/atm-20-5362DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7944315PMC
February 2021

WISP1 Protects Against Chondrocyte Senescence and Apoptosis by Regulating αvβ3 and PI3K/Akt Pathway in Osteoarthritis.

DNA Cell Biol 2021 Apr 1;40(4):629-637. Epub 2021 Mar 1.

Department of Orthopaedics, Yiyang Central Hospital, Yiyang, China.

Our study aimed at validating the effect of WISP1 on osteoarthritis (OA) and the pathway involved in the WISP1-induced protection against OA. The expression of WISP1 was measured by immunohistochemical analyses. We found that WISP1 expression was shown to be upregulated within human OA cartilage compared with controls. WISP1 expression was related to knee OA severity. rhWISP1 inhibited OA chondrocyte senescence and apoptosis , which was reversed by the αvβ3 antibody and PI3K/Akt inhibitor LY294002. WISP1 overexpression induced by knee injection of LiCI could also prevent the senescence and apoptosis of rat chondrocytes. Safranin-O staining and Mankin score revealed that WISP1 overexpression can protect rat chondrocytes from degeneration. Nearly opposite results were obtained in the treatment of ICG-001 and siRNA-WISP1 . These data strongly suggest that WISP1 can protect against the senescence and apoptosis of chondrocytes via modulating the αvβ3 receptor and PI3K/Akt signaling pathway within OA. Therefore, the development of specific activators of WISP1 may present the value of an underlying OA treatment.
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http://dx.doi.org/10.1089/dna.2020.5926DOI Listing
April 2021

Role of peroxisome proliferator-activated receptors in osteoarthritis (Review).

Mol Med Rep 2021 02 23;23(2). Epub 2020 Dec 23.

Department of Sports Medicine, Shenzhen Second People's Hospital/The First Affiliated Hospital of Shenzhen University Health Science Center, Shenzhen, Guangdong 518035, P.R. China.

Osteoarthritis (OA) is the most common form of arthritis, for which treatment options are not always satisfactory, since complete cure for OA is not yet possible. A better understanding of OA pathogenesis is thus important. The peroxisome proliferator‑activated receptor (PPAR) plays a major regulatory role in lipid metabolism and energy homeostasis. This review article aimed to discuss the biological function of PPARs, and their role in regulating OA progression, as well as the therapeutic aspect of PPARs in OA. Studies indicate that PPARs regulate articular cartilage homeostasis through the modulation of various signaling pathways, and reduce the inflammatory responses in human OA cartilage. Furthermore, the deficiency of PPARs in the articular cartilage might be responsible for the acceleration of severe OA by increasing catabolic activity and suppression of chondroprotection. Therapeutic applications of PPAR‑agonists can thus reduce the development of cartilage lesions by inhibiting the synthesis of various catabolic and inflammatory factors involved in the pathogenesis of OA. PPARs are thus important proteins in OA regulation, which may have significant importance in OA therapeutics.
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http://dx.doi.org/10.3892/mmr.2020.11798DOI Listing
February 2021

Pathological changes of frozen shoulder in rat model and the therapeutic effect of PPAR-γ agonist.

J Orthop Res 2021 04 1;39(4):891-901. Epub 2020 Dec 1.

Department of Sports Medicine, The First Affiliated Hospital of Shenzhen University, Shenzhen Second People's Hospital, Shenzhen, Guangdong, China.

Frozen shoulder is a common shoulder disorder characterized by a gradual increase of pain and a limited range of motion. However, its pathophysiologic mechanisms remain unclear and there is no consensus as to the most effective treatment. The purpose of the study was to investigate the effect of transforming growth factor-β (TGF-β) on fibrosis and inflammatory response of the shoulder joint of rat models and to explore the therapeutic effect of the peroxisome proliferator-activated receptor-γ (PPAR-γ) agonist. In the study, the effect of PPAR-γ agonist CDDO-IM treatment on cell proliferation, migration, and extracellular matrix proteins synthesis (vimentin, α-smooth muscle actin, collagen I, and collagen III) were tested by cell proliferation test, scratches test, real-time quantitative polymerase chain reaction, and Western blot analysis. The frozen shoulder was also established on the rat model by injecting adenovirus-TGF-β1 into rats' shoulder capsule. Pathological changes of the frozen shoulder tissue of the experimental group and PPAR-γ agonist treatment group were evaluated. The stiffness of joints of the three groups was tested. Inflammatory mediators' expression including cyclooxygenase-1, interleukin-1β, and tumor necrosis factor-α of the shoulder was tested by enzyme-linked immunosorbent assay, and the expression of extracellular matrix proteins was evaluated by hematoxylin and eosin staining and immunohistochemistry. The results showed that pathological changes of the frozen shoulder in the rat model include an abnormal proliferation of fibroblasts, infiltration of inflammatory cells, and disorder of fibrous structure, while rosiglitazone reduced the severity of the frozen shoulder in the treatment group. Clinically, PPAR-γ agonists may be a promising target for the treatment of the frozen shoulder.
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http://dx.doi.org/10.1002/jor.24920DOI Listing
April 2021

Let-7f promotes the differentiation of neural stem cells in rats.

Am J Transl Res 2020 15;12(9):5752-5761. Epub 2020 Sep 15.

Department of Pediatrics, Xiangya Hospital, Central South University Changsha 410008, Hunan, China.

Hypoxic-ischemic brain damage (HIBD) is the major recognized perinatal cause of neurological morbidity in full-term new borns. Neural stem cells (NSCs) have been extensively studied because of their clinical applications in treating neuro degenerative diseases and brain injuries, including HIBD, while microRNAs (miRNAs) are deemed critical regulators of the proliferation and differentiation of NSCs. However, the role of let-7f in NSC differentiation remains unknown. Our study aims to investigate the role of let-7f in the differentiation of NSCs and brain development in rats and hence to explore the therapeutic potential of let-7f in the treatment of HIBD. The quantitative real-time polymerase chain reaction (qRT-PCR) was applied to assess the expressions of let-7f, and western blot was performed to detect GFAP, Tuj1 and Nestin in rat brains at postnatal day 1, 8 and 14 (n=12 per time point). The NSCs isolated from the brains of rat fetuses at gestational day 15 were transduced with lenti virus expressing let-7f or let-7f inhibitor so as to observe altered expressions of let-7f, GFAP, Tuj1 and Nestin. A gradually-increasing expression of let-7f was detected by qRT-PCR in rat brain tissues during postnatal brain development. Increased levels of GFAP and Tuj1, while a decreased level of Nestin, were detected by western blot in let-7f-overexpressing NSCs. In contrast, the cells expressing the let-7f inhibitor exhibited lower levels of GFAP and Tuj1, while a higher level of Nestin, compared with control cells. Therefore, let-7f is involved in brain development and promotes the differentiation of NSCs in rats.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7540113PMC
September 2020

Impaired bone defect and fracture healing in dystrophin/utrophin double-knockout mice and the mechanism.

Am J Transl Res 2020 15;12(9):5269-5282. Epub 2020 Sep 15.

Department of Orthopaedic Surgery, McGovern Medical School, University of Texas Health Science Center at Houston Houston, TX, USA.

This study investigated the role of muscle damage in bone defect healing using skull and tibial double-defect and tibial fracture models in dystrophin/Utrophin double-knockout (dKO-Hom) mice. The skull and tibia bone defect and fracture healing was monitored using micro-CT, histology, immuohistochemistry and quantitative PCR. We found the skull defect healing is not impaired while the tibial defect healing was delayed at day 7 in the dKO-Hom group compared to wild-type (WT) group as revealed by micro-CT. Mechanistically, the number of osteoclasts and osteoblasts significantly decreased in the defect area in dKO-Hom group compared to WT group on day 21. DKO-Hom mice showed higher mortality after fracture (6/12) and significantly impaired fracture healing compared to the other groups as revealed by the micro-CT parameters of the calluses. Histology showed higher osteoclast number in the calluses of dKO-Hom mice than other groups. Furthermore, dKO-Hom mice showed down-regulation of 15-Pgdh, Il-4, Bmp7, and Bmp9 at 10 days after tibia fracture and BMP6 and 7 in the muscle. In conclusion, the long bone defect and fracture healing are impaired in dKO-Hom mice which demonstrated significantly muscle sarcopenia and related with disturbance of osteoclastogenesis and osteoblastogenesis. The impaired tibial fracture healing was associated with down-regulation of several genes in the muscle.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7540103PMC
September 2020

A retrospective study to compare the clinical effects of individualized anatomic single- and double-bundle anterior cruciate ligament reconstruction surgery.

Sci Rep 2020 09 7;10(1):14712. Epub 2020 Sep 7.

Department of Sports Medicine, Key Laboratory of Tissue Engineering of Shenzhen, Shenzhen Second People's Hospital/The First Affiliated Hospital of Shenzhen University Health Science Center, Shenzhen, Guangdong, China.

To evaluate the clinical efficacy of single- and double- bundle individualized anatomic anterior cruciate ligament (ACL) reconstruction, we retrospectively analyzed the data and charts of 920 patients with ACL rupture who received individualized anatomic ACL reconstruction surgery at our center. All of the patients underwent arthroscopic ACL reconstruction with autologous hamstring tendons. The patients were divided into two groups: the single-bundle individualized anatomic reconstruction group (N = 539), and the double-bundle individualized anatomic reconstruction group (N = 381). The IKDC, Lysholm and Tegner scores were used to subjectively evaluate the function of the knee joint during the postoperative follow-up. The Lachman test, pivot shift test and KT-3000 were used to objectively evaluate the stability of the knee. All 920 patients participated in clinical follow-up (average duration: 27.91 ± 3.61 months) achieved satisfied outcomes with few complications. The postoperative IKDC, Lysholm and Tegner scores, and the objective evaluation of knee joint stability were significantly improved compared to the preoperative status in both groups (P < 0.05). No statistically significant difference was observed between the two groups at the final follow-up (P > 0.05). Therefore, no difference in terms of the IKDC, Lysholm and Tegner score, or KT-3000 was observed between the individualized anatomic single- and double-bundle ACL reconstruction techniques. Both techniques can be used to restore the stability and functionality of the knee joint with satisfactory short-term efficacy.
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http://dx.doi.org/10.1038/s41598-020-71721-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7477567PMC
September 2020

Gender differences in tibial fractures healing in normal and muscular dystrophic mice.

Am J Transl Res 2020 15;12(6):2640-2651. Epub 2020 Jun 15.

Department of Orthopaedic Surgery, McGovern Medical School, University of Texas Health Science Center at Houston Houston, TX 77054, USA.

Duchenne muscular dystrophy (DMD) patients have a high fracture risk and poor fracture healing. The dystrophin () mouse is a murine model of DMD and exhibits delayed bone fracture healing. Since our research team has shown that adult stem cells, such as muscle-derived stem cells, display a gender difference in their osteogenic potential with the male cells being more osteogenic, we hypothesize that a potential gender differences may exist during bone healing in normal and mice. To test this hypothesis, wild-type (WT) and mice underwent tibial fracture surgery and microCT live scanning biweekly. The mice were sacrificed at 6 weeks post-surgery and the calluses were collected for histological analysis. To further investigate the mechanism, another two sets of mice were sacrificed at 10 days after fracture for RNA extraction and gene expression analysis and histology. MicroCT results showed, at 6 weeks post- surgery, the calluses were larger but showed less remodeling in both normal and male mice when compared to females, at the same time point. However, females had higher callus bone volume density and an increase in osteoclast (OCs) number. At 10 days after fracture surgery, male mice had formed larger calluses, whereas females formed well-remodeled calluses with more osteoblasts and a greater bone area for both WT and mice. Higher IGF-1 expression was observed in male mice when compared to their female counterparts, whereas female WT mice had higher BMP-9 expression when compared to WT males. In conclusion, male mice formed larger bone calluses than females during tibial fracture healing for both WT and mice. This may be attributed to higher IGF-1 expression, activation of Wnt/β-catennin signaling pathway and greater OB numbers during callus formation. Female mice achieved better bone remodeling in the regenerated bone with higher bone quality due to increased OC numbers that promote faster remodeling of the fracture calluses, and higher BMP-9 expression levels. Therefore, gender is one of many factors that need to be considered for both animal and human bone research.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7344076PMC
June 2020

Letter regarding "HemiCAP® implantation after failed previous surgery for osteochondral lesions of the talus".

Foot Ankle Surg 2020 06 28;26(4):477-478. Epub 2020 Apr 28.

Department of Sports Medicine, The First Affiliated Hospital of Shenzhen University, Health Science Center, Shenzhen Second People's Hospital, Shenzhen 518000, Guangdong Province, China.

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http://dx.doi.org/10.1016/j.fas.2020.03.006DOI Listing
June 2020

Construction and characterization of an adenoviral vector encoding human bone morphogenetic protein-2.

J Int Med Res 2020 Mar;48(3):300060520910320

Department of Sports Medicine, Shenzhen Second People's Hospital/The First Affiliated Hospital of Shenzhen University, Shenzhen, Guangdong, China.

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http://dx.doi.org/10.1177/0300060520910320DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7105281PMC
March 2020

The time-dependent effects of bipolar radiofrequency energy on bovine articular cartilage.

J Orthop Surg Res 2020 Mar 12;15(1):106. Epub 2020 Mar 12.

Department of Sports Medicine, the First Affiliated Hospital of Shenzhen University, Shenzhen Second People's Hospital, Shenzhen, 518035, Guangdong, China.

Purpose: The purpose of this study was to compare the effect of bipolar radiofrequency energy (bRFE) on chondroplasty at the different time durations in an in vitro experiment that simulated an arthroscopic procedure.

Methods: Six fresh bovine knees were used in our study. Six squares were marked on both the medical and lateral femoral condyles of each femur. Each square was respectively treated with bRFE for 0 s, 10 s, 20 s, 30 s, 40 s and 50 s. Full-thickness articular cartilage specimens were harvested from the treatment areas. Each specimen was divided into three distinct parts: one for hematoxylin/eosin staining histology, another for cartilage surface contouring assessment via scanning electron microscopy (SEM), and the last one for glycosaminoglycan (GAG) content measurement.

Results: bRFE caused time-correlated damage to chondrocytes, and GAG content in the cartilage was negatively correlated to exposure time. bRFE caused time-correlated damage to chondrocytes. The GAG content in the cartilage negatively correlated with the exposure time. The sealing effect positively correlated with the exposure time. Additionally, it took at least 20 s of radiofrequency exposure to render a smooth cartilage surface and a score of 2 (normal) in the scoring system used.

Conclusion: bRFE usage in chondroplasty could effectively trim and polish the cartilage lesion area; however, it induces a dose-dependent detrimental effect on chondrocytes and metabolic activity that negatively correlated with the treatment time. Therefore, cautions should be taken in the use of bRFE for treatment of articular cartilage injury.
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http://dx.doi.org/10.1186/s13018-020-01626-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7069051PMC
March 2020

Macrophages in osteoarthritis: pathophysiology and therapeutics.

Am J Transl Res 2020 15;12(1):261-268. Epub 2020 Jan 15.

Department of Orthopaedics, Xiangya Hospital, Central South University Changsha 410008, Hunan, China.

Osteoarthritis (OA) is the most common cause of disability in worldwide population, which is characterized by cartilage breakdown, synovial fibrosis, osteophyte formation and pain. Synovial inflammation is usually found in both early and late stages in most of the OA patients. Macrophages, the major component of the mononuclear phagocyte system, play a critical role in OA pathogenesis through the induction of inflammatory mediators, growth factors and proteinases. So, drugs that can target macrophages and macrophage-associated inflammatory pathways at an appropriate stage may help to inhibit or slow down the progression of OA. However, despite an emerging role of synovial macrophages in OA pathogenesis, little is known about the biology of synovial tissue macrophages, and attempts to target macrophages therapeutically have had limited success. But the use of selective targets of macrophages may minimize the side effects and support the promising therapeutic strategy in the treatment of OA. More pre-clinical animal models and clinical trials are necessary to evaluate the role of selective targets of macrophages in the prevention and treatment of OA. This review article discusses the association of macrophages in OA development and possible OA therapeutics by targeting macrophages.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7013211PMC
January 2020

Biologically Regulated Marrow Stimulation by Blocking TGF-β1 With Losartan Oral Administration Results in Hyaline-like Cartilage Repair: A Rabbit Osteochondral Defect Model.

Am J Sports Med 2020 03 6;48(4):974-984. Epub 2020 Feb 6.

Investigation performed at Center for Regenerative Sports Medicine, Steadman Philippon Research Institute, Vail, Colorado, USA.

Background: Microfracture or bone marrow stimulation (BMS) is often the first choice for clinical treatment of cartilage injuries; however, fibrocartilage, not pure hyaline cartilage, has been reported because of the development of fibrosis in the repair tissue. Transforming growth factor β1 (TGF-β1), which can promote fibrosis, can be inhibited by losartan and potentially be used to reduce fibrocartilage.

Hypothesis: Blocking TGF-β1 would improve cartilage healing in a rabbit knee BMS model via decreasing the amount of fibrocartilage and increasing hyaline-like cartilage formation.

Study Design: Controlled laboratory study.

Methods: An osteochondral defect was made in the patellar groove of 48 New Zealand White rabbits. The rabbits were divided into 3 groups: a defect group (defect only), a BMS group (osteochondral defect + BMS), and a BMS + losartan group (osteochondral defect + BMS + losartan). For the rabbits in the BMS + losartan group, losartan was administrated orally from the day after surgery through the day of euthanasia. Rabbits were sacrificed 6 or 12 weeks postoperatively. Macroscopic appearance, microcomputed tomography, histological assessment, and TGF-β1 signaling pathway were evaluated at 6 and 12 weeks postoperatively.

Results: The macroscopic assessment of the repair revealed that the BMS + losartan group was superior to the other groups tested. Microcomputed tomography showed superior healing of the bony defect in the BMS + losartan group in comparison with the other groups. Histologically, fibrosis in the repair tissue of the BMS + losartan group was significantly reduced when compared with the other groups. Results obtained with the modified O'Driscoll International Cartilage Repair Society grading system yielded significantly superior scores in the BMS + losartan group as compared with both the defect group and the BMS group ( value: 15.8, < .001, = .012, respectively). TGF-β1 signaling and TGF-β-activated kinase 1 of the BMS + losartan group were significantly suppressed in the synovial tissues.

Conclusion: By blocking TGF-β1 with losartan, the repair cartilage tissue after BMS was superior to the other groups and consisted primarily of hyaline cartilage. These results should be easily translated to the clinic because losartan is a Food and Drug Administration-approved drug and it can be combined with the BMS technique for optimal repair of chondral defects.

Clinical Relevance: Biologically regulated marrow stimulation by blocking TGF-β1 (oral intake of losartan) provides superior repair via decreasing fibrocartilage formation and resulting in hyaline-like cartilage as compared with outcomes from BMS only.
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http://dx.doi.org/10.1177/0363546519898681DOI Listing
March 2020

High bone microarchitecture, strength, and resistance to bone loss in MRL/MpJ mice correlates with activation of different signaling pathways and systemic factors.

FASEB J 2020 01 27;34(1):789-806. Epub 2019 Nov 27.

Department of Orthopaedic Surgery, The Brown Foundation Institute of Molecular Medicine, McGovern Medical School, University of Texas Health Science Center at Houston, Houston, Texas.

The MRL/MpJ mice have demonstrated an enhanced tissue regeneration capacity for various tissues. In the present study, we systematically characterized bone microarchitecture and found that MRL/MpJ mice exhibit higher bone microarchitecture and strength compared to both C57BL/10J and C57BL/6J WT mice at 2, 4, and 10 months of age. The higher bone mass in MRL/MpJ mice was correlated to increased osteoblasts, decreased osteoclasts, higher cell proliferation, and bone formation, and enhanced pSMAD5 signaling earlier during postnatal development (2-month old) in the spine trabecular bone, and lower bone resorption rate at later age. Furthermore, these mice exhibit accelerated fracture healing via enhanced pSMAD5, pAKT and p-P38MAPK pathways compared to control groups. Moreover, MRL/MpJ mice demonstrated resistance to ovariectomy-induced bone loss as evidenced by maintaining higher bone volume/tissue volume (BV/TV) and lower percentage of bone loss later after ovariectomy. The consistently higher serum IGF1 level and lower RANKL level in MRL/MpJ mice may contribute to the maintenance of high bone mass in uninjured and injured bone. In conclusion, our results indicate that enhanced pSMAD5, pAKT, and p-P38MAPK signaling, higher serum IGF-1, and lower RANKL level contribute to the higher bone microarchitecture and strength, accelerated healing, and resistance to osteoporosis in MRL/MpJ mice.
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http://dx.doi.org/10.1096/fj.201901229RRDOI Listing
January 2020

Modified Arthroscopic Latarjet Procedure: Suture-Button Fixation Achieves Excellent Remodeling at 3-Year Follow-up.

Am J Sports Med 2020 01 25;48(1):39-47. Epub 2019 Nov 25.

Department of Sports Medicine, Shenzhen Second People's Hospital, First Affiliated Hospital of Shenzhen University, Shenzhen, China.

Background: Some studies have advocated the use of suture-button fixation during the Latarjet procedure to reduce complications associated with screw fixation. However, the sample size of these studies is relatively small, and their follow-up period is short.

Purpose: To investigate the efficacy of the suture-button Latarjet procedure with at least 3 years of follow-up and remodeling of the coracoid graft.

Study Design: Case series; Level of evidence, 4.

Methods: A total of 152 patients who underwent the suture-button Latarjet procedure between February 2013 and February 2016 were selected, and 128 patients who met the inclusion criteria were enrolled in this study. Preoperative and postoperative clinical results were assessed. The position and healing condition of the coracoid graft and arthropathy of the glenoid and humeral head were also assessed using radiography and 3-dimensional computed tomography (CT).

Results: The mean follow-up time was 40.3 ± 5.8 months. There were 102 patients included in this study. The mean visual analog scale score for pain during motion, the American Shoulder and Elbow Surgeons score, the Rowe score, and the Walch-Duplay score were improved considerably. A total of 100 grafts achieved bone union. The overall absorption rate was 12.6% ± 4.3%. Graft absorption mostly occurred on the edge and outside the "best-fit" circle of the glenoid. A vertical position was achieved in 98 grafts (96% of all cases) immediately postoperatively, with the mean graft midline center at the 4 o'clock position. In the axial view, CT showed that 89 grafts were flush to the glenoid, whereas 2 and 11 grafts were fixed medially and laterally, respectively. In all cases, the bone graft and glenoid tended to extend toward each other to form concentric circles during the remodeling process. During follow-up observations, the height of the 11 grafts that were positioned laterally (ie, above the glenoid level) exhibited a wave-curved change. No arthropathy was observed in any patient.

Conclusion: Patient outcomes were satisfactory after the modified arthroscopic suture-button Latarjet technique. Graft absorption mostly occurred on the edge and outside the "best-fit" circle of the glenoid. The graft exhibited the phenomenon of ectatic growing when it fused with the glenoid and finally remodeled to a new concentric circle with the humeral head analogous to the original glenoid. Grafts positioned laterally did not cause arthropathy of the joints within the period of the study.
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http://dx.doi.org/10.1177/0363546519887959DOI Listing
January 2020

A pilot study of blood supply of the coracoid process and the coracoid bone graft after Latarjet osteotomy.

Biosci Rep 2019 11;39(11)

Department of Sports Medicine, The First Hospital Affiliated to Shenzhen University, Shenzhen Second People's Hospital, Shenzhen, Guangdong, China.

Latarjet osteotomy is still one of the most reliable and commonly used surgeries in treating recurrent anterior shoulder dislocation. The coracoid process (CP) is the main structure of this surgery. However, the blood supply of CP is not fully understood, and the extent of destruction of blood supply of coracoid bone graft after Latarjet osteotomy procedure is still controversial. Five embalmed cadaveric upper limbs specimens were employed for macro observation of the blood supply of CP. The conjoint tendon (CT) and CP interface were dissected for histology. Sixteen fresh frozen shoulder specimens were used for perfusion and micro CT scanning. Eight specimens were used to present the whole vessel structure of CP. The other eight underwent Latarjet osteotomy procedure. The coracoid bone grafts in both groups were scanned to clarify the remnant blood supply. It was found that the CP was nourished by supra-scapular artery (SSA), thoracic-acromial artery and branch from second portion of the axillary artery (AA). After Latarjet osteotomy procedure, no artery from CT was detected to penetrate the CP at its attachment. Only in one specimen the blood vessel that originated from the CT penetrated the bone graft at the inferior side. Therefore, most of the blood supply was destroyed although there is a subtle possibility that the vessels derived from the CT nourished the inferior side of the CP. In a nutshell, CP is a structure with rich blood supply. The traditional Latarjet osteotomy procedure would inevitably cut off the blood supply of the coracoid bone graft.
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http://dx.doi.org/10.1042/BSR20190929DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6851520PMC
November 2019

RhoA/ROCK pathway: implication in osteoarthritis and therapeutic targets.

Am J Transl Res 2019 15;11(9):5324-5331. Epub 2019 Sep 15.

Department of Orthopedics, Xiangya Hospital, Central South University Changsha 410008, Hunan, China.

Ras homolog gene family, member A (RhoA) and its downstream effector Rho-associated protein kinase (ROCK) play important roles in multiple cellular processes, but abnormal activation of this pathway have been reported to be involved in various types of diseases, including osteoarthritis (OA). This article focused to review the RhoA/ROCK association and its functional role in OA development, and possible therapeutics of OA by targeting this pathway. We have explored the databases like Pubmed, Google Scholar, Web of Science and SCOPUS, and collected the papers on Rho/ROCK and their relationship with OA, and reviewed comprehensively. Studies revealed that the abnormal activation of RhoA/ROCK signaling is involved in early phase response to abnormal mechanical stimuli, which is thought to be a contributory factor to OA progression. RhoA/ROCK interacts with OA pathological factors and induces cartilage degeneration through the degradation of chondrocyte extracellular matrix (ECM). As the RhoA/ROCK activity can affect bone formation by triggering cartilage degradation, it may represent a possible therapeutic target to treat OA. Interestingly, several pharmaceutical companies are investing in the development of RhoA/ROCK inhibitors for the treatment of OA. However, a few in vivo experiments have been successfully conducted to demonstrate the potential value of RhoA/ROCK pathway inhibition in the treatment of OA. This review provides an insight into the functional role of Rho/ROCK pathway, and indicates that targeting this pathway might be promising in future OA treatment.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6789288PMC
September 2019

[Effect of isokinetic training of thigh muscle group on graft remodeling after anterior cruciate ligament reconstruction].

Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi 2019 Sep;33(9):1088-1094

Department of Sports Medicine, the First Affiliated Hospital of Shenzhen University (Shenzhen Second People's Hospital), Shenzhen Guangzhou, 518000, P.R.China;Sports Medicine Engineering Technology Research Center of Guangdong Province, Shenzhen Guangdong, 518000,

Objective: To investigate the effect of isokinetic training of thigh muscle group on graft remodeling after anterior cruciate ligament (ACL) reconstruction, and summarize the relevant rules to guide the clinic.

Methods: Between August 2016 and December 2016, forty patients underwent arthroscopic ACL reconstruction using hamstring tendon were randomly divided into isokinetic group and control group ( =20). The two groups of patients underwent staged rehabilitation treatment. The isokinetic group replaced the traditional intervention with the corresponding isokinetic strength training from 3 to 6 months after operation, and the traditional rehabilitation intervention was used in the control group. Finally, 12 cases of isokinetic group and 12 cases of control group with complete follow-up were enrolled in study. There was no significant difference in gender, age, body mass index, side of injury, the interval between injury and operation, and preoperative International Knee Documentation Committee (IKDC) score between the two groups ( >0.05). The peak torque (PT) of knee extension and flexion and hamstring quadriceps ratio (H/Q) were measured at 3 months, 6 months, 12 months, and the second-look arthroscopy. The MRI examination was performed at the same time to evaluate graft remodeling. The shape, tension, and degree of vascularization of grafts were observed under arthroscopy. The grafts were harvested and observed by HE staining.

Results: The invertal between ACL reconstruction and the second-look arthroscopy was (23.57±3.23) months in isokinetic group and (23.22±3.56) months in control group, showing no significant difference between the two groups ( >0.05). At the second-look arthroscopy, the IKDC score was 90.45±4.73 in isokinetic group and 89.32±4.54 in control group, showing significant differences when compared with preoperative scores in the two groups ( <0.05). But there was no significant difference between the two groups ( =0.868, =0.404). At 3 months after operation, there was no significant difference in the PT of knee extension and flexion between the two groups ( >0.05). At 6 months, 12 months, and the second-look arthroscopy, the PT of knee extension and flexion in isokinetic group were higher than those in control group ( <0.05). The H/Q at 6 months and 12 months were higher in isokinetic group than in control group, and the differences were significant ( <0.05). There was no significant difference in MRI score between the two groups at 3 months, 6 months, and the second-look arthroscopy ( >0.05). The MRI score at 12 months was significantly higher in isokinetic group than in control group ( <0.05). At the second-look arthroscopy, there was no significant difference in the arthroscopic score between the two groups ( >0.05), and the histological score of the isokinetic group was superior to the control group ( <0.05).

Conclusion: On the basis of regular rehabilitation training, using the isokinetic training system to develop a suitable post-surgical isokinetic rehabilitation training program is helpful in early muscle strength recovery, early graft remodeling, and even long-term histological results after ACL reconstruction.
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http://dx.doi.org/10.7507/1002-1892.201902059DOI Listing
September 2019

Characterization of a novel polyvinyl alcohol/chitosan porous hydrogel combined with bone marrow mesenchymal stem cells and its application in articular cartilage repair.

BMC Musculoskelet Disord 2019 May 29;20(1):257. Epub 2019 May 29.

Department of Sports Medicine, the First Affiliated Hospital of Shenzhen University, Shenzhen Second People's Hospital, Shenzhen, 518035, Guangdong, China.

Background: Different substances are combined to compensate for each other's drawbacks and create an appropriate biomaterial. A novel Polyvinyl alcohol (PVA)/chitosan (CS) porous hydrogel was designed and applied to the treatment of osteochondral defects.

Methods: Hydrogels of various PVA/CS ratios were tested for physiochemical and mechanical properties in addition to cytotoxicity and biocompatibility. The hydrogels with the best PVA/CS ratio were used in the animal study. Osteochondral defects were created at the articular cartilage of 18 rabbits. They were assigned to different groups randomly (n = 6 per group): the osteochondral defect only group (control group), the osteochondral defect treated with hydrogel group (HG group), and the osteochondral defect treated with hydrogel loaded with bone marrow mesenchymal stem cells (BMSCs) group (HG-BMSCs group). The cartilage was collected for macro-observation and histological evaluation at 12 weeks after surgery.

Results: The Hydrogel with PVA/CS ratio of 6:4 exhibited the best mechanical properties; it also showed stable physical and chemical properties with porosity and over 90% water content. Furthermore, it demonstrated no cytotoxicity and was able to promote cell proliferation. The HG-BMSCs group achieved the best cartilage healing.

Conclusions: The novel PVA/CS porous composite hydrogel could be a good candidate for a tissue engineering material in cartilage repair.
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http://dx.doi.org/10.1186/s12891-019-2644-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6540438PMC
May 2019

Interosseous tendon inflammation of rheumatoid arthritis: what's the real meaning?

Ann Rheum Dis 2020 07 17;79(7):e83. Epub 2019 May 17.

The First Affiliated Hospital of Shenzhen University, Shenzhen Second People's Hospital, Shenzhen, China

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http://dx.doi.org/10.1136/annrheumdis-2019-215559DOI Listing
July 2020

The effect of earthworm extract on mice S180 tumor growth and apoptosis.

Biomed Pharmacother 2019 Jul 14;115:108979. Epub 2019 May 14.

Department of Orthopaedics, Xiangya Hospital, Central South University, Changsha 410008, Hunan, China; National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha 410008, Hunan, China. Electronic address:

Great efforts have been made to explore the potential treatment for cancers, and the most common therapies include surgery, chemotherapy and radiotherapy. As an alternative medication, earthworms have drawn increased attention considering its abundance in resource, easy access and minor side effects compared to traditional therapies. However, few studies had focused on the antitumor effect of earthworm-derived components. The purpose of this study is to investigate whether earthworm extract has an effect on tumor cell apoptosis and growth. Earthworm extract (EE) was purified through multiple steps of centrifugation and chromatography. Mice were inoculated with ascitic fluid derived from mice inoculated with S180 sarcoma tumor cells and fed orally with different amounts of EE for 25 days. Tumor samples were analyzed for size and cell apoptosis. And we found that the weight and sizes of tumor decreased gradually as the amount of EE administered increased. More apoptotic cells and lowered level of lactate dehydrogenase (LDH), a biomarker of tumor invasiveness, was detected in EE-treated group than the untreated group. Our results suggested that EE could dramatically promote tumor apoptosis and reduce tumor size in vivo, suggesting a novel alternative therapy for cancer patients.
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http://dx.doi.org/10.1016/j.biopha.2019.108979DOI Listing
July 2019

Anterior Cruciate Ligament Reconstruction in a Rabbit Model Using a Decellularized Allogenic Semitendinous Tendon Combined with Autologous Bone Marrow-Derived Mesenchymal Stem Cells.

Stem Cells Transl Med 2019 09 11;8(9):971-982. Epub 2019 May 11.

Department of Arthroscopic Surgery, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China.

As a regular adoptable material for anterior cruciate ligament (ACL) reconstruction, free tendon allograft exhibits unsatisfactory outcomes, such as retarded ligamentization and tendon-bone integration. The application of bone marrow-derived mesenchymal stem cells (BMSCs), as well as a decellularized free tendon allograft developed by our group, was proven to be effective in improving ACL reconstruction results. This study aimed to investigate the efficacy and feasibility of decellularized allogenic semitendinous tendon (ST) combined with autologous BMSCs used as a substitute to free tendon allograft in a rabbit model. This study finally shows that the decellularized allogenic ST combined with autologous BMSCs could significantly improve ACL reconstruction results compared with allograft. Stem Cells Translational Medicine 2019;8:971&982.
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http://dx.doi.org/10.1002/sctm.18-0132DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6708071PMC
September 2019

The efficiency and safety of steroid addition to multimodal cocktail periarticular injection in knee joint arthroplasty: a meta-analysis of randomized controlled trials.

Sci Rep 2019 05 7;9(1):7031. Epub 2019 May 7.

Department of Sports Medicine, the First Affiliated Hospital of Shenzhen University, Shenzhen Second People's Hospital, Shenzhen, Guangdong, China.

Steroids are frequently used for postoperative pain relief without definite evidence. This study was conducted to assess the pain management effect of the addition of steroids to a multimodal cocktail periarticular injection (MCPI) in patients undergoing knee arthroplasty and evaluate their safety. Pubmed, Embase, and Cochrane Library were searched through April, 2018. A total of 918 patients from ten randomized controlled trials (RCTs) were ultimately included. Compared with placebo groups, steroids application could effectively relieve pain on postoperative day (POD)1; decrease C-Reactive protein (CRP) level on POD3; improve range of motion (ROM) in postoperative 5 days; reduce morphine consumption, achieve earlier straight leg raising (SLR), and shorten the length of stay (LOS) in hospital. With regards to adverse effects, it did not increase the risk of postoperative infection, postoperative nausea and vomiting (PONV), or other complications. However, no significant difference in pain relief, ROM, or increased Knee Society Knee Function Scores were found during long-term follow up. Overall, this meta-analysis ensured the efficiency and safety of steroids with MCPI in knee arthroplasty patients during the early postoperative period.
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http://dx.doi.org/10.1038/s41598-019-43540-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6505038PMC
May 2019

Characterization of articular cartilage homeostasis and the mechanism of superior cartilage regeneration of MRL/MpJ mice.

FASEB J 2019 08 1;33(8):8809-8821. Epub 2019 May 1.

Department of Orthopedic Surgery, Brown Foundation Institute of Molecular Medicine, McGovern Medical School, University of Texas Health Science Center at Houston, Houston, Texas, USA.

This study investigated articular cartilage (AC) homeostasis and different signaling pathways involved in the superior cartilage regeneration of Murphy Roths large (MRL/MpJ) mice previously reported. We collected uninjured and destabilized medial meniscus (DMM)-injured knees from 8-wk-old C57BL/6J and MRL/MpJ mice. We used micro-computed tomography (microCT), histology, and immunohistochemistry to evaluate AC homeostasis and repair. We used the ear punch model to investigate the role of angiogenesis and inflammation in the superior healing of MRL/MpJ mice. We found fewer β-catenin and more pSMAD5 positive cells in the uninjured AC of MRL/MpJ mice than that from C57BL/6J mice. MRL/MpJ mice exhibited better AC repair in DMM-induced OA, as indicated by microCT results, Alcian blue, and Safranin O staining. Mechanistically, fewer β-catenin, pSMAD2-, pSMAD3-, a disintegrin and metalloproteinase with thrombospondin motifs 4-, matrix metalloproteinase (MMP) 9-, and MMP13-positive cells and more proliferating cell nuclear antigen- and pSMAD5-positive cells were found in the DMM-injured AC in MRL/MpJ mice than in normal mice. The accelerated ear wound healing of MRL/MpJ mice correlated with enhanced angiogenesis and macrophage polarization toward the M2a phenotype through elevated IL-10 and IL-4 expressing cells. Collectively, our study revealed that down-regulation of pSMAD2/3, β-catenin, and MMPs and up-regulation of pSMAD5 and M2a macrophage polarization contribute to the enhanced cartilage repair observed in MRL/MpJ mice.-Deng, Z., Gao, X., Sun, X., Amra, S., Lu, A., Cui, Y., Eltzschig, H. K., Lei, G., Huard, J. Characterization of articular cartilage homeostasis and the mechanism of superior cartilage regeneration of MRL/MpJ mice.
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http://dx.doi.org/10.1096/fj.201802132RRDOI Listing
August 2019

The role of sirtuin 1 and its activator, resveratrol in osteoarthritis.

Biosci Rep 2019 05 10;39(5). Epub 2019 May 10.

Department of Emergency Medicine, Xiangya Hospital, Central South University, Changsha, Hunan, China

Osteoarthitis (OA) is the most common aging-related joint pathology; the aging process results in changes to joint tissues that ultimately contribute to the development of OA. Articular chondrocytes exhibit an aging-related decline in their proliferative and synthetic capacity. Sirtuin 1 (SIRT 1), a longevity gene related to many diseases associated with aging, is a nicotinamide adenine dinucleotide (NAD)-dependent protein deacetylase and master metabolic regulator. Along with its natural activator resveratrol, SIRT 1 actively participates in the OA pathological progress. SIRT 1 expression in osteoarthritic cartilage decreases in the disease progression of OA; it appears to play a predominantly regulatory role in OA. SIRT 1 can regulate the expression of extracellular matrix (ECM)-related proteins; promote mesenchymal stem cell differentiation; play anti-catabolic, anti-inflammatory, anti-oxidative stress, and anti-apoptosis roles; participate in the autophagic process; and regulate bone homeostasis in OA. Resveratrol can activate SIRT 1 in order to inhibit OA disease progression. In the future, activating SIRT 1 via resveratrol with improved bioavailability may be an appropriate therapeutic approach for OA.
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http://dx.doi.org/10.1042/BSR20190189DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6509056PMC
May 2019

The morphology and histology study on rabbit degenerated medial meniscus after posterior cruciate ligament rupture.

Biosci Rep 2019 01 25;39(1). Epub 2019 Jan 25.

Department of Orthopaedics, Xiangya Hospital, Central South University, Changsha, Hunan, China

The morphology and histology changes in the medial meniscus after posterior cruciate ligament (PCL) rupture are poorly understood. Forty-eight rabbits were divided into matched mode pairs; each rabbit had an experimental side, in which the PCL was transacted, and a control side. At the 4, 8, 16 and 24 weeks after the PCL transection, each of the 12 rabbits was killed. Histology was performed to detect the expression of the tissue inhibitors of metalloproteinases-1 (TIMP-1), matrix metalloproteinase (MMP)-1 and MMP-13 in the medial meniscus. We found that medial meniscus displayed significant degenerative characteristics in morphology. The histological evaluation of the degeneration found that the expression levels of TIMP-1, MMP-1 and MMP-13 in the medial meniscus were higher in the experiment side than those in the control side (<0.05). The expression of both TIMP-1 and MMP-13 was initially elevated and then decreased. The MMP-1 expression reached its peak swiftly and then maintained a relatively high level. There were clear time-dependent degenerative changes in the histology of the medial meniscus after PCL rupture. The high expression of TIMP-1, MMP-1 and MMP-13 in the cartilage may be responsible for the degeneration, and PCL rupture may trigger meniscus degradation and ultimately osteoarthritis.
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http://dx.doi.org/10.1042/BSR20181843DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6350045PMC
January 2019