Publications by authors named "Xiaozhou Ying"

31 Publications

Decursin alleviates the aggravation of osteoarthritis via inhibiting PI3K-Akt and NF-kB signal pathway.

Int Immunopharmacol 2021 Apr 18;97:107657. Epub 2021 Apr 18.

Department of Orthopedics Surgery, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, China. Electronic address:

Osteoarthritis (OA) is a common joint disease that takes joint degeneration or aging as its pathological basis, and joint swelling, pain or dysfunction as its main clinical manifestations. Decursin (DE), the major active component isolated from Angelica gigas Nakai, has been demonstrated to possess anti-inflammatory effect in many diseases. But, the specific physiological mechanism of DE on OA is not clear yet. Therefore, the object of this study was to assess the therapeutic effect of DE on OA, and to explore its potential anti-inflammatory mechanisms. In vitro cell experiments, the inflammatory response in chondrocytes is mediated via interleukin-1β (IL-1β), which led to abnormal secretion of pro-inflammatory factors, such as prostaglandin E2 (PGE), interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-α), cyclooxygenase-2 (COX-2), nitric oxide (NO) and inducible nitric oxide synthase (iNOS). These cytokines were all decreased by the preconditioning of DE in a dose-dependent form of 1, 5, and 10 µM. Moreover, DE could restrain IL-1β-mediated inflammatory reaction and the collapse of extracellular matrix (ECM) via reducing the secretion of ADAMTS (a disintegrin and metalloproteinase with thrombospondin motifs) and MMPs (matrix metalloproteinases). In short, DE restrained IL-1β-mediated abnormal excitation of PI3K/AKT/NF-κB axis. Furthermore, molecular docking analysis showed that DE has a strong binding affinity with the inhibitory targets of PI3K. In vivo animal studies, DE treatment could helped to improve destruction of articular cartilage and decreased the serum inflammatory factor levels in an operationally induced mouse OA model. To sum up, these data obtained from the experiment indicate that DE has good prospects for the treatment of osteoarthritis.
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http://dx.doi.org/10.1016/j.intimp.2021.107657DOI Listing
April 2021

Possible osteoprotective effects of myricetin in STZ induced diabetic osteoporosis in rats.

Eur J Pharmacol 2020 Jan 19;866:172805. Epub 2019 Nov 19.

Department of Orthopaedic Surgery, The Second Affiliated Hospital of Soo Chow University, 1055, Sanxiang Road, Suzhou, 215000, China; Osteoporosis Institute of Soo Chow University, 1055, Sanxiang Road, Suzhou, 215000, China. Electronic address:

Myricetin is a flavonoid which has many pharmacological effects. However, to date there is no evidence study on the effect of myricetin in diabetic condition. This study was aimed to investigate whether myricetin could protect against diabetic osteoporosis in streptozotocin induced rats. Female Wistar rats were randomly allocated to four equal groups: diabetic group (DG), diabetic group with myricetin (50 mg per kilogram per day), (D) diabetic group with myricetin (100 mg/kg/day) and normal control group (CG). Body weight was recorded once a week. After treatment with myricetin for 12 weeks, serum biochemical analyses, the microarchitecture of femora, and histological changes were evaluated. We found that the bone mineral density (BMD) of myricetin (100 mg per kilogram per day)treatment group significantly increased than in the diabetic group (P < 0.05). The alkaline phosphatase and osteocalcin were markedly blocked in diabetic rats relative to normal control group (P < 0.05); however, the inhibition was prevented by the myricetin treatment group. Results also showed that myricetin treatment could dramatically improve trabecular bone microarchitecture through increasing bone mass such as trabecular number (Tb.N), bone volume per tissue volume (BV/TV), and decreasing that of structure model index (SMI) and trabecular separation (Tb.Sp), comparing with the control group. We also found that myricetin could significantly lower the oxidative damage and up-regulate the activity of superoxide dismutase (SOD) and catalase activity. In summary, we showed that myricetin can effectively improve abnormal bone metabolism in streptozotocin induced rats, which may provide a beneficial medicine on diabetic bone disease.
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http://dx.doi.org/10.1016/j.ejphar.2019.172805DOI Listing
January 2020

Activation of Nrf2/HO-1 signal with Myricetin for attenuating ECM degradation in human chondrocytes and ameliorating the murine osteoarthritis.

Int Immunopharmacol 2019 Oct 17;75:105742. Epub 2019 Jul 17.

Department of Orthopaedics, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, West Xueyuan Road 109#, Wenzhou 325027, Zhejiang Province, China; Zhejiang Provincial Key Laboratory of Orthopaedics, Wenzhou, Zhejiang Province, China; The Second School of Medicine, Wenzhou Medical University, Wenzhou, Zhejiang Province, China. Electronic address:

Background: Osteoarthritis (OA), one of the prevailing joint degenerative disorders, contributes to the disability around the world. However, no effective therapeutic was introduced currently. Myricetin was reported to possess the function of anti-inflammatory, anti-diabetic and anti-cancer. Thus, we investigate the protection role of myricetin in OA progression and the potential molecular mechanism in present study.

Methods: Quantitative realtime PCR and western blotting were performed to evaluate the expression of MMP-13, Aggrecan, iNOS, and COX-2 at both gene and protein levels. An enzyme-linked immunosorbent assay was used to evaluate the levels of inflammatory factors (PGE2, TNF-α, and IL-6). The PI3K/AKT, Nrf2/HO-1 and nuclear factor kappa B (NF-κB) signaling pathways were analyzed by western blotting, and immunofluorescence was used to assess the expression of Nrf2, Collagen II and MMP13. The in vitro effect of myricetin was evaluated by intragastric administration into a mouse osteoarthritis model induced by destabilization of the medial meniscus.

Results: Myricetin not only inhibited the generation of inflammatory mediators and cytokines such as nitric oxide (NO), prostaglandin E2 (PGE2), TNF-α and IL-6, but also suppressed the production of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) in human chondrocytes under IL-1β stimulation. Moreover, Metalloproteinase 13 (MMP13) and thrombospondin motifs 5 (ADAMTS5), which resulted in the degradation of cartilage, were also suppressed in chondrocytes with the treatment of myricetin. To explore the potential mechanism, we found out that myricetin suppressed NF-κB signaling pathway through Nrf2/HO-1 axis in human chondrocytes. Besides, myricetin regulated the Nrf2 signaling pathway through PI3K/Akt pathway. In addition, in vivo study demonstrated that myricetin could ameliorated the progression of OA in mice DMM model through PI3K/Akt mediated Nrf2 signaling pathway.

Conclusion: Taken together, our data first demonstrated that myricetin possesses the therapeutic potential on OA through PI3K/Akt mediated Nrf2/HO-1 signaling pathway.
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http://dx.doi.org/10.1016/j.intimp.2019.105742DOI Listing
October 2019

Correction to: Plumbagin Prevents IL-1β-Induced Inflammatory Response in Human Osteoarthritis Chondrocytes and Prevents the Progression of Osteoarthritis in Mice.

Inflammation 2019 Aug;42(4):1511-1514

Department of Orthopaedic Surgery, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, 109 Xueyuan Xi Road, Wenzhou, 325000, China.

The original version of this article contained mistakes, and the authors would like to correct them. The correct details are given below.
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http://dx.doi.org/10.1007/s10753-019-00989-0DOI Listing
August 2019

Ligustilide alleviated IL-1β induced apoptosis and extracellular matrix degradation of nucleus pulposus cells and attenuates intervertebral disc degeneration in vivo.

Int Immunopharmacol 2019 Apr 18;69:398-407. Epub 2019 Feb 18.

Department of Orthopaedics, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, West Xueyuan Road 109#, Wenzhou 325027, Zhejiang Province, China; Zhejiang Provincial Key Laboratory of Orthopaedics, Wenzhou, Zhejiang Province, China; The Second School of Medicine, Wenzhou Medical University, Wenzhou, Zhejiang Province, China. Electronic address:

Intervertebral disc degeneration is a multifactorial and complicated degenerative disease that imposes a huge economic burden on society. However, there is no effective treatment that can delay and reverse the progression of disc degeneration. The inflammatory response causes the death of nucleus pulposus cells and the degradation of extracellular matrix are main factors of intervertebral disc degeneration. Ligustilide is a bioactive phthalide that is said to have an anti-inflammatory effect and anti-apoptosis effect on various disorders. Therefore, we further explored the protective effect of ligustilide on intervertebral disc degeneration and its potential mechanism. In this study, we found that ligustilide inhibited apoptosis, suppressed the expression of related inflammatory mediators (iNOS and COX-2) and decreased the expression of inflammatory cytokines (TNF-a and IL-6) in nucleus pulposus cells under IL-1β stimulation. At the same time, the degradation of extracellular matrix of nucleus pulposus cells induced by IL-1β was inhibited. In addition, we also found that ligustilide inhibits the inflammation response by inhibiting the NF-κB signaling pathway. Moreover, TUNEL assay and histological analysis showed that ligustilide could inhibit the apoptosis of nucleus pulposus cells and ameliorate the progression of intervertebral disc degeneration in punctured Rat IDD model. In summary, ligustilide may become a new potential treatment for intervertebral disc degeneration.
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http://dx.doi.org/10.1016/j.intimp.2019.01.004DOI Listing
April 2019

The therapeutic effect of fraxetin on ethanol-induced hepatic fibrosis by enhancing ethanol metabolism, inhibiting oxidative stress and modulating inflammatory mediators in rats.

Int Immunopharmacol 2018 Mar 2;56:98-104. Epub 2018 Feb 2.

Department of ultrasound imaging, the First Affiliated Hospital of Wenzhou Medical University, China. Electronic address:

The present study was designed to investigate the possible protective effects of fraxetin against ethanol induced liver fibrosis in rats. Rats were underwent intragastric administration of ethanol (5.0-9.5 g/kg) once a day for 24 weeks. Effect of fraxetin against ethanol induced liver fibrosis was investigated by giving 20 or 50 mg/kg fraxetin. At the end of experiment, the livers were collected for histopathological analyses, protein extraction, and enzymatic activities. Our results indicated that fraxetin significantly corrected ethanol-induced hepatic fibrosis, as evidenced by the decrease in serum ALT and AST, the attenuation of histopathological changes. Fraxetin also expedited ethanol metabolism by enhancing the alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) activities. Besides, fraxetin alleviated lipid peroxidation, enhanced hepatic antioxidant capabilities, inhibited CYP2E1 activity, and reduced the inflammatory mediators, including TNF-α and IL-1β via up-regulation of hemeoxygenase-1 (HO-1) protein. In summary, the hepatoprotection of fraxetin is mostly attributed to its antioxidant capability, alcohol metabolism, and anti-inflammation effect.
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http://dx.doi.org/10.1016/j.intimp.2018.01.027DOI Listing
March 2018

Silibinin protects against osteoarthritis through inhibiting the inflammatory response and cartilage matrix degradation and .

Oncotarget 2017 Nov 24;8(59):99649-99665. Epub 2017 Aug 24.

Department of Orthopaedic Surgery, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou 325000, China.

Osteoarthritis (OA) is a degenerative joint disease characterized by cartilage degradation and inflammation. Silibinin, a polyphenolic flavonoid derived from fruits and seeds of , has been reported to possess various potent beneficial biological effects, such as antioxidant, anti-cancer, hepatoprotective and anti-inflammatory activities. However, the anti-inflammatory effects of silibinin on OA have not been reported. This study aimed to assess the effects of silibinin on OA both and . In this study, we found that silibinin significantly inhibited the nterleukin-1β (IL-1β)-induced production of nitric oxide (NO), prostaglandin E2 (PGE2), tumor necrosis factor-α (TNF-α) and IL-6, expression of cyclooxygenase2 (COX-2), inducible nitric oxide synthase (iNOS), matrix metalloproteinase-1 (MMP-1), MMP-3, MMP-13, a disintegrin and metalloproteinase with thrombospondin motifs-4 (ADAMTS-4) and ADAMTS-5, degradation of aggrecan and collagen-II in human OA chondrocytes. Furthermore, silibinin dramatically suppressed IL-1β-stimulated phosphatidylinositol 3 kinase/ protein kinase B (PI3K/Akt) phosphorylation and nuclear factor-kappa B (NF-kB) activation in human OA chondrocytes. In addition, treatment of silibinin not only prevented the destruction of cartilage and the thickening of subchondral bone but also relieved synovitis in mice OA models. Also, the immunohistochemistry results showed that silibinin significantly decreased the expression of MMP-13 and ADAMTS-5 and increased the expression of collagen-II and aggrecan in mice OA. Taken together, these results suggest that silibinin may be a potential agent in the treatment of OA.
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http://dx.doi.org/10.18632/oncotarget.20587DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5725122PMC
November 2017

Chrysin Attenuates IL-1β-Induced Expression of Inflammatory Mediators by Suppressing NF-κB in Human Osteoarthritis Chondrocytes.

Inflammation 2017 Aug;40(4):1143-1154

Department of Orthopaedic Surgery, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, 109 Xueyuan Xi Road, Wenzhou, 325000, China.

Osteoarthritis (OA) is a degenerative joint disease characterized by cartilage degradation and inflammation. Chrysin, a natural flavonoid extracted from honey and propolis, has been reported to have anti-inflammatory effects. However, the anti-inflammatory effects of chrysin on OA have not been reported. This study aimed to assess the effects of chrysin on human OA chondrocytes. Human OA chondrocytes were pretreated with chrysin (1, 5, 10 μM) for 2 h and subsequently stimulated with IL-1β for 24 h. Production of NO, PGE2, MMP-1, MMP-3, MMP-13, ADAMTS-4, and ADAMTS-5 was evaluated by the Griess reaction and ELISAs. The messenger RNA (mRNA) expression of COX-2, iNOS, MMP-1, MMP-3, MMP-13, ADAMTS-4, ADAMTS-5, aggrecan, and collagen-II was measured by real-time PCR. The protein expression of COX-2, iNOS, p65, p-p65, IκB-α, and p-IκB-α was detected by Western blot. The protein expression of collagen-II and p65 nuclear translocation was evaluated by immunofluorescence. We found that chrysin significantly inhibited the IL-1β-induced production of NO and PGE2; expression of COX-2, iNOS, MMP-1, MMP-3, MMP-13, ADAMTS-4, and ADAMTS-5; and degradation of aggrecan and collagen-II. Furthermore, chrysin dramatically blocked IL-1β-stimulated IκB-α degradation and NF-κB activation. Taken together, these results suggest that chrysin may be a potential agent in the treatment of OA.
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http://dx.doi.org/10.1007/s10753-017-0558-9DOI Listing
August 2017

The protective effects of silibinin in the treatment of streptozotocin-induced diabetic osteoporosis in rats.

Biomed Pharmacother 2017 May 6;89:681-688. Epub 2017 Mar 6.

Department of Orthopaedic Surgery, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou 325000, China. Electronic address:

Diabetic osteoporosis (DO) is a complication of diabetes mellitus. Our previous study showed that silibinin can attenuate high glucose mediated human bone marrow stem cells dysfunction through antioxidant effect. However, no study has yet investigated the effect of silibinin in diabetic rats. Therefore, we assessed the effects of silibinin on bone characteristics in streptozotocin-induced diabetic rats. The aim of our study was to determine whether providing silibinin in the different supplementation could prevent bone loss in diabetic rats or not. Rats were randomly divided into four groups: (1) control group (CG) (n=10); (2) diabetic group (DG) (n=10); (3) diabetic group with 50mgkgday of silibinin orally (DG-50) (n=10); and (4) diabetic group with 100mgkgday of silibinin orally (DG-100) (n=10). 12 weeks after streptozotocin (STZ) injection, the femora from all rats were assessed and oxidative stress was evaluated. Bone mineral density was significantly decreased in diabetic rats; these effects were prevented by treatment with silibinin (100mgkgday orally). Similarly, in the DG and DG-50 groups, changes in microarchitecture of femoral metaphysis assessed by microcomputed tomography demonstrated simultaneous existence of diabetic osteoporosis; these impairments were prevented by silibinin (100mgkgday orally). In conclusion, silibinin supplementation may have potential use as a possible therapy for maintaining skeletal health and these results can enhance the understanding of diabetic osteoporosis induced by diabetes.
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http://dx.doi.org/10.1016/j.biopha.2017.02.018DOI Listing
May 2017

Plumbagin Prevents IL-1β-Induced Inflammatory Response in Human Osteoarthritis Chondrocytes and Prevents the Progression of Osteoarthritis in Mice.

Inflammation 2017 Jun;40(3):849-860

Department of Orthopaedic Surgery, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, 109 Xueyuan Xi Road, Wenzhou, 325000, China.

Inflammation and inflammatory cytokines have been reported to play vital roles in the development of osteoarthritis (OA). Plumbagin, a quinonoid compound extracted from the roots of medicinal herbs of the Plumbago genus, has been reported to have anti-inflammatory effects. However, the anti-inflammatory effects of plumbagin on OA have not been reported. This study aimed to assess the effects of plumbagin on human OA chondrocytes and in a mouse model of OA induced by destabilization of the medial meniscus (DMM). In vitro, human OA chondrocytes were pretreated with plumbagin (2, 5, 10 μM) for 2 h and subsequently stimulated with IL-1β for 24 h. Production of NO, PGE2, MMP-1, MMP-3, and MMP-13 was evaluated by the Griess reagent and ELISAs. The messenger RNA (mRNA) expression of COX-2, iNOS, MMP-1, MMP-3, MMP-13, aggrecan, and collagen-II was measured by real-time PCR. The protein expression of COX-2, iNOS, p65, p-p65, IκBα, and p-IκBα was detected by Western blot. The protein expression of collagen-II was evaluated by immunofluorescence. In vivo, the severity of OA was determined by histological analysis. We found that plumbagin significantly inhibited the IL-1β-induced production of NO and PGE2; expression of COX-2, iNOS, MMP-1, MMP-3, and MMP-13; and degradation of aggrecan and collagen-II. Furthermore, plumbagin dramatically suppressed IL-1β-stimulated NF-κB activation. In vivo, treatment of plumbagin not only prevented the destruction of cartilage and the thickening of subchondral bone but also relieved synovitis in mice OA models. Taken together, these results suggest that plumbagin may be a potential agent in the treatment of OA.
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http://dx.doi.org/10.1007/s10753-017-0530-8DOI Listing
June 2017

Comparison of percutaneous cannulated screw fixation and calcium sulfate cement grafting versus minimally invasive sinus tarsi approach and plate fixation for displaced intra-articular calcaneal fractures: a prospective randomized controlled trial.

BMC Musculoskelet Disord 2016 07 15;17:288. Epub 2016 Jul 15.

Department of Orthopaedics Surgery, The Second Affiliated Hospital of Wenzhou Medical University, NO. 109, Xue Yuan West Road, Lucheng District, Wenzhou, Zhejiang Province, 325027, China.

Background: The management of displaced intra-articular calcaneal fractures (DIACFs) remains challenging and controversial. A prospective randomized controlled trial was conducted to compare percutaneous reduction, cannulated screw fixation and calcium sulfate cement (PR+CSC) grafting with minimally invasive sinus tarsi approach and plate fixation (MISTA) for treatment of DIACFs.

Methods: Ultimately, 80 patients with a DIACFs were randomly allocated to receive either PR+CSC (N = 42) or MISTA (N = 38). Functional outcomes were evaluated using the American Orthopaedic Foot and Ankle Society (AOFAS) hindfoot scores. Radiological results were assessed using plain radiographs and computed tomography (CT) scans, and postoperative wound-related complications were also recorded.

Results: The average time from initial injury to operation and the average operation time in the PR+CSC group were both significantly shorter than those in the MISTA group (p < 0.05). There were significantly fewer complications in the PR+CSC group than those in the MISTA group (7.1 % vs 28.9 %, p < 0.001). The calcaneal width immediate postoperatively and at the final follow-up in the MISTA group were obviously improved compared to those in the PR+CSC group (p < 0.001). The variables of sagittal motion and hindfoot motion of the AOFAS scoring system in the PR+CSC group were significantly higher than those in the MISTA group (p < 0.05). The good and excellent results in the two groups were comparable for Sanders Type-II calcaneal fractures, but the good to excellent rate in the MISTA group was significantly higher for Sanders Type-III fractures (p < 0.05).

Conclusion: The clinical outcomes are comparable between the two minimally invasive techniques in the treatment of Sanders Type-II DIACFs. The PR+CSC grafting is superior to the MISTA in terms of the average time between initial injury and operation, operation time, wound-related complications and subtalar joint activity. However, the MISTA has its own advantages in improving the calcaneal width, providing a more clear visualization and accurate reduction of the articular surface, especially for Sanders Type-III DIACFs.

Trial Registration: ChiCTRIOR16008512 . 21 May 2016.
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http://dx.doi.org/10.1186/s12891-016-1122-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4946135PMC
July 2016

Closed Reduction and Percutaneous Fixation of Calcaneal Fractures in Children.

Orthopedics 2016 Jul 27;39(4):e744-8. Epub 2016 Apr 27.

Open reduction and internal fixation has been widely used to treat displaced intra-articular calcaneus fractures in children. However, the complications of surgical trauma and the wound created through the extended lateral approach cannot be ignored. This study analyzed the outcomes of displaced intra-articular calcaneal fractures in children treated with closed reduction and percutaneous fixation. Medical records of pediatric patients who had displaced intra-articular calcaneus fractures and underwent closed reduction and percutaneous fixation at the study institution between January 2008 and January 2013 were reviewed. Preoperative radiographs and computed tomography scans were used to evaluate and classify the fractures. Clinical outcomes and radiographic findings were assessed at postoperative follow-up. The study included 14 displaced intra-articular calcaneal fractures in 11 patients (7 boys and 4 girls). Mean patient age was 11.18 years (range, 6-16 years), and average follow-up time was 42.8 months postoperatively (range, 12-72 months). There were 6 tongue-type fractures and 8 joint depression-type fractures, based on the Essex-Lopresti classification, and there were 11 type II and 3 type III fractures, based on the Sanders classification. Average Böhler angle was 8.00° (range, -5° to 18°) preoperatively and 30.79° (range, 26° to 40°) postoperatively (P<.001). Average subjective American Orthopaedic Foot and Ankle Society hindfoot score was 65.7 (range, 52-68). No patients had wound breakdown or infection. In the treatment of displaced intra-articular calcaneal fractures in pediatric patients, closed reduction and percutaneous fixation achieved good outcomes, with few complications. [Orthopedics. 2016; 39(4):e744-e748.].
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http://dx.doi.org/10.3928/01477447-20160421-05DOI Listing
July 2016

Percutaneous Screw Fixation of Crescent Fracture-Dislocation of the Sacroiliac Joint.

Orthopedics 2015 Nov;38(11):e976-82

Crescent fracture-dislocation of the sacroiliac joint (CFDSIJ) is a type of lateral compression pelvic injury associated with instability. Open reduction and internal fixation is a traditional treatment of CFDSIJ. However, a minimally invasive method has never been reported. The purpose of this study was to assess the outcome of closed reduction and percutaneous fixation for different types of CFDSIJ and present their clinical outcome. The authors reviewed 117 patients diagnosed with CFDSIJ between July 2003 and July 2013. Closed reduction and percutaneous fixation was performed in 73 patients. Treatment selection was based on Day's fracture classification. For type I fractures, fixation perpendicular to the fracture line were performed. For type II fractures, crossed fixation was performed. For type III fractures, fixation was performed with iliosacral screws. Forty-four patients were treated by open reduction and plate fixation. Demographics, fracture pattern distribution, blood loss, incision lengths, revision surgeries, radiological results, and functional scores were compared. All 117 patients were followed for more than 6 months (mean, 14 months [range, 6-24 months]). Blood loss, extensive exposure, duration of posterior ring surgery, duration of hospital stay, and infection rates were lower in the closed group (P<.01). Patients in the closed group achieved better functional performance (P<.01). There were no significant differences in reduction quality (P=.32), revision surgery rates (P=.27), and iatrogenic neurologic injuries (P=.2) between the 2 groups. The authors' results indicate that closed reduction and percutaneous fixation is a safe and effective surgical method for CFDSIJ.
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http://dx.doi.org/10.3928/01477447-20151020-05DOI Listing
November 2015

Protective effects of sesamin on liver fibrosis through antioxidative and anti-inflammatory activities in rats.

Immunopharmacol Immunotoxicol 2015 ;37(5):465-72

c Department of Infectious Diseases , the First Affiliated Hospital of Wenzhou Medical University , Wenzhou , China , and.

Context: Sesamin (Ses) from Sesamun indicum seeds has potent antioxidants and anti-inflammatory effects.

Objective: This study focused on the antioxidant and anti-inflammatory effects of Ses on Carbon tetrachloride (CCl4)-induced hepatic fibrosis in experimental rats and the potential mechanism underlying the activation of NF-kB pathway.

Materials And Methods: Hepatic fibrosis was induced by interaperitoneally (i.p.) administered with 20% CCl4 in corn oil (2 mL/kg for 8 weeks) in rats. After 8 weeks, activities of serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), and total bilirubin (TBIL) were checked. The levels of protein carbonyls and antioxidant enzymes such as superoxide dismutase (SOD) and GSH-Px were determined after Ses administration. H&E and Masson's trichrome staining for histopathological changes of liver tissues were observed. Western blotting was used to detect expression of IL-6, cyclooxygenase-2 (COX-2), and NF-kB activation. Finally, the levels of hydroxyproline in liver tissues were also determined.

Results: Ses decreased the release of liver enzymes - ALT, AST, and TBIL, reduced protein carbonyls, attenuated the reduction of SOD and GSH-Px activities induced by CCl4 in the liver tissue. It also significantly reduced the levels IL-6 and COX-2 in the liver caused by CCl4 by inhibition of NF-kB activation. Histological results indicated that Ses significantly improved the pathological lesions of liver fibrosis.

Conclusions: Ses exerted hepatoprotective effects possibly due to the antioxidant effect and suppressing the NF-kB activation.
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http://dx.doi.org/10.3109/08923973.2015.1085064DOI Listing
August 2016

Silibinin alleviates high glucose-suppressed osteogenic differentiation of human bone marrow stromal cells via antioxidant effect and PI3K/Akt signaling.

Eur J Pharmacol 2015 Oct 8;765:394-401. Epub 2015 Sep 8.

Trauma Center of the Affiliated Hospital of Hainan Medical College, Haikou 570100, China.

High glucose is one of the possible causes for osteoporosis and fracture in diabetes mellitus. Our previous study showed that silibinin can increase osteogenic effect by stimulating osteogenic genes expression in human bone marrow stem cells (hBMSCs). However, no study has yet investigated the effect of silibinin on osteogenic differentiation of hBMSCs cultured with high glucose. The aim of this study was to evaluate the influence of high glucose on osteogenic differentiation of hBMSCs and to determine if silibinin can alleviate those effects. In this study, the hBMSCs were cultured in an osteogenic medium with physiological (normal glucose, NG, 5.5mM) or diabetic (high glucose, HG, 30mM). The effects of silibinin on HG-induced osteogenic differentiation were evaluated by alkaline phosphatas (ALP) activity assay, Von Kossa staining and real time-polymerase chain reaction. HG-induced oxidative damage was also assessed. Western blot were performed to examine the role of PI3K/Akt pathway. We demonstrated that HG suppressed osteogenic differentiation of hBMSCs, manifested by a decrease in expression of osteogenic markers and an increase of oxidative damage markers including reactive oxygen species and lipid peroxide (MDA). Remarkably, all of the observed oxidative damage and osteogenic dysfunction induced by HG were inhibited by silibinin. Furthermore, the PI3K/Akt pathway was activated by silibinin. These results demonstrate that silibinin may attenuate HG-mediated hBMSCs dysfunction through antioxidant effect and modulation of PI3K/Akt pathway, suggesting that silibinin may be a superior drug candidate for the treatment of diabetes related bone diseases.
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http://dx.doi.org/10.1016/j.ejphar.2015.09.005DOI Listing
October 2015

Radiographic diagnosis of sagittal plane rotational displacement in pelvic fractures: a cadaveric model and clinical case study.

Arch Orthop Trauma Surg 2015 Aug 1;135(8):1093-9. Epub 2015 Jul 1.

Department of Orthopaedic Surgery, The Second Affiliated Hospital of Wenzhou Medical University, 109 Xue yuan xi Road, Wenzhou, 325000, China.

Purposes: Our objective was to measure the sagittal plane rotational (flexion and extension) displacement of hemipelvis radiologically and analyze the ratio of flexion and extension displacement of unstable pelvic fractures.

Methods: We used 8 cadaveric models to study the radiographic evidence of pelvic fractures in the sagittal plane. We performed pelvic osteotomy on 8 cadavers to simulate anterior and posterior pelvic ring injury. Radiological data were measured in the flexion and extension group under different angles (5°, 10°, 15°, 20°, and 25°). We retrospectively reviewed 164 patients who were diagnosed with a unilateral fracture of the pelvis. Pelvic ring displacement was identified and recorded radiographically in cadaveric models.

Results: The flexion and extension displacement of pelvic fractures was measured in terms of the vertical distance of fracture from the top of iliac crest to the pubic tubercle (CD) or from the top of iliac crest to the lowest point of ischial tuberosity (AB). Fifty-seven pelves showed flexion displacement and 15 showed extension displacement. Closed reduction including internal fixation and external fixation was successfully used in 141 cases (86.0 %). The success rates of closed reduction in flexion and extension displacement groups were 77 and 73 %, respectively, which were lower than in unstable pelvic ring fractures.

Conclusions: The sagittal plane rotation (flexion and extension) displacement of pelvic fractures could be measured by special points and lines on the radiographs. Minimally invasive reduction should be based on clearly identified differences between the sagittal plane rotation and the vertical displacement of pelvic fractures.
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http://dx.doi.org/10.1007/s00402-015-2251-5DOI Listing
August 2015

SeMet mediates anti-inflammation in LPS-induced U937 cells targeting NF-κB signaling pathway.

Inflammation 2015 Apr;38(2):736-44

Department of Orthopedic Surgery, School of Medicine, The Second Affiliated Hospital, Zhejiang University, 88 Jiefang Road, Hangzhou, 310009, Zhejiang, China,

In previous studies, selenium (Se) was reported to play critical roles in anti-inflammatory activities. Nevertheless, limited information could be obtained during inflammation about selenomethionine (SeMet) in U937 human macrophage cells. The purpose of this study was to investigate the effects of SeMet on the inflammatory responses to lipopolysaccharide (LPS)-induced U937 macrophage cells and the signaling pathways targeted. U937 cells were pretreated with SeMet (1 μM) and subsequently induced with LPS (1 μg/ml) for 24 h. In the cell counting kit-8 assay (CCK-8), SeMet significantly inhibits the proliferation of U937 cells. SeMet also inhibited the production of nitric oxide (NO) and prostaglandin E2 (PGE2) stimulated by LPS. In the Western blot assay and real-time polymerase chain reaction (RT-PCR), SeMet significantly reduced protein expression and production of inducible NO synthase (iNOS), tumor necrosis factor-alpha (TNF-α), and COX-2 in U937 cells. Furthermore, SeMet markedly suppressed the LPS-mediated activation of nuclear factor-kappa B (NF-κB) by blocking the degradation of inhibitor-κB proteins (IκBα) and lessening the translocations of P50 subunit content of NF-κB in the nucleus. These findings suggested the anti-inflammatory activity of SeMet in U937 cells; indicating that SeMet might be a potential treatment for inflammation therapy.
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http://dx.doi.org/10.1007/s10753-014-9984-0DOI Listing
April 2015

Engineering scaffolds integrated with calcium sulfate and oyster shell for enhanced bone tissue regeneration.

ACS Appl Mater Interfaces 2014 Aug 30;6(15):12177-88. Epub 2014 Jul 30.

Department of Orthopaedic Surgery, Second Affiliated Hospital, School of Medicine, Zhejiang University , Hangzhou 310009, Zhejiang China.

Engineering scaffolds combinging natural biomineral and artificially synthesized material hold promising potential for bone tissue regeneration. In this study, novel bioactive calcium sulfate/oyster shell (CS/OS) composites were prepared. Comparing to CS scaffold, the CS/OS composites with a controllable degradation rate displayed enhanced mineral nodule formation, higher alkaline phosphate (ALP) activity and increased proliferation rate while treated osteocytes. In CS/OS composites group, elevated mRNA levels of key osteogenic genes including bone morphogenetic protein-2 (BMP-2), runt-related transcription factor 2 (Runx2), osterix (Osx), and osteocalcin (OCN) were observed. Furthermore, The up-regulation of BMP-2 and type I collagen (COL-I) was observed for CS/OS composites relative to a CS group. Scaffolds were implanted into critical-sized femur cavity defects in rabbits to investigate the osteogenic capacity of the composites in vivo. The CS/OS scaffolds with proper suitable times and mechanical strength strongly promoted osteogenic tissue regeneration relative to the regeneration capacity of CS scaffolds, as indicated by the results of histological staining. These results suggest that the OS-modified CS engineering scaffolds with improved mechanical properties and bioactivity would facilitate the development of a new strategy for clinic bone defect regeneration.
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http://dx.doi.org/10.1021/am501448tDOI Listing
August 2014

Myricetin enhances osteogenic differentiation through the activation of canonical Wnt/β-catenin signaling in human bone marrow stromal cells.

Eur J Pharmacol 2014 Sep 27;738:22-30. Epub 2014 May 27.

Trauma center of the Affiliated Hospital of Hainan Medical College, Haikou 570100, China.

Myricetina flavonoid compound, has been reported to possess antioxidative, antiproliferative and anti-inflammatory effects. However, no study has yet investigated the effect of myricetin on osteogenic differentiation of human bone marrow stem cells (hBMSCs). This study was designed to investigate the effects of myricetin on osteogenic differentiation of hBMSCs in vitro. Cell viability was analyzed by MTT and osteogenic differentiation was evaluated by alkaline phosphatase (ALP) activity assay, Alizarin red S dye, real time-polymerase chain reaction (RT-PCR) and Western blot analysis. We found that the ALP activity and the mineralization of hBMSCs were enhanced by treatment with myricetin. Myricetin increased the mRNA expressions of Osteocalcin (OCN), Collagen type I (COL-I), ALP and Runt-related transcription factor 2 (RUNX2). Additionally, we found that myricetin activated the Wnt/β-catenin pathway and increased the expression of several downstream genes including T-cell factor-1(TCF-1) and lymphoid enhancer factor-1 (LEF-1). Depletion of β-catenin almost completely blocked the positive role of myricetin on osteogenic differentiation. Taken together, our findings suggest that myricetin enhanced osteogenic differentiation of hBMSCs by activating the Wnt/β-catenin signaling. The study may aid in the development of a therapeutic approach utilizing myricetin for the enhancement of bone health and prevention of osteoporosis.
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http://dx.doi.org/10.1016/j.ejphar.2014.04.049DOI Listing
September 2014

Cordycepin prevented IL-β-induced expression of inflammatory mediators in human osteoarthritis chondrocytes.

Int Orthop 2014 Jul 12;38(7):1519-26. Epub 2013 Dec 12.

Department of Orthopaedic Surgery, The Second Affiliated Hospital of Wenzhou Medical College, 109 Xue yuan xi Road, Wenzhou, 325000, China,

Purpose: Cordycepin, a nucleoside derivative isolated from Cordyceps, has been reported to exert anti-inflammatory, antitumor, antidiabetic and renoprotective effects. Osteoarthritis (OA) is a degenerative joint disease with an inflammatory component that drives the degradation of cartilage extracellular matrix. This study aimed to assess the effects of cordycepin on human OA chondrocytes.

Methods: In this study, human OA chondrocytes were pretreated with cordycepin at 10, 50 or 100 μM and subsequently stimulated with interleukin-1β (IL-1β) (5 ng/ml) for 24 h. Production of prostaglandin E2 (PGE2) and nitric oxide (NO) were evaluated by the Griess reaction and an enzyme-linked immunosorbent assay (ELISA). Gene expression of matrix metalloproteinase (MMP)-13, IL-6, inducible nitric oxide synthase (iNOS) and cyclo-oxygenase (COX-2) was measured by real-time polymerase chain reaction (PCR). MMP-13 and IL-6 proteins in culture medium were determined using cytokine-specific ELISA. Western immunoblotting was used to analyse the iNOS and COX-2 protein production in culture medium. Nuclear factor kappa-B (NF-κB) activity regulation was explored using Western immunoblotting.

Results: Pretreatment with cordycepin significantly inhibited the production of PGE2 and NO induced by IL-1β. Cordycepin also significantly decreased the IL-1β-stimulated gene expression and production of MMP-13, IL-6, iNOS and COX-2 in OA chondrocytes. Pretreatment with cordycepin attenuated IL-1β-induced activation of NF-κB by suppressing degradation of its inhibitory protein nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, alpha (IκB-α) in the cytoplasm.

Conclusions: We show for the first time the anti-inflammatory activity of cordycepin in human OA chondrocytes. Thus, with this unique profile of actions, cordycepin may prove to be a potentially attractive and new therapeutic/preventive agent for OA.
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http://dx.doi.org/10.1007/s00264-013-2219-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4071485PMC
July 2014

Phosphoserine promotes osteogenic differentiation of human adipose stromal cells through bone morphogenetic protein signalling.

Cell Biol Int 2014 Mar 15;38(3):309-17. Epub 2013 Nov 15.

Department of Orthopaedic Surgery, The Second Affiliated Hospital of Wenzhou Medical College, Wenzhou, 325000, China.

Phosphoserine has potential effectiveness as a simple substrate in preparing bone replacement materials, which could enhance bone forming ability. However, there is a need to investigate the independent effect of phosphoserine on osteogenic differentiation of human adipose stem cells (hADSCs). hADSCs were cultured in an osteogenic medium with phosphoserine. Cell proliferation was analysed by CCK8 and osteogenic differentiation was measured by alkaline phosphatase (ALP) activity, von Kossa staining and real time-polymerase chain reaction (RT-PCR). No stimulatory effect of phosphoserine on cell proliferation was noted at Days 1, 4 and 7. Deposition of calcium increased after the addition of phosphoserine. mRNA expression of type I collagen (COL-I), alkaline phosphatase (ALP), osteocalcin (OCN), Osterix, bone morphogenetic protein-2 (BMP-2) and RUNX2 increased markedly with phosphoserine treatment. The BMP-2 antagonist, noggin, and its receptor kinase inhibitors, dorsomorphin and LDN-193189, attenuated phosphoserine-promoted ALP activity. BMP-responsive and Runx2-responsive reporters were activated by phosphoserine treatment. Thus phosphoserine can promote osteogenic differentiation of hADSCs, probably by activating BMP and Runx2 pathways, which could be a promising approach for enhancing osteogenic capacity of cell-based construction in bone tissue engineering.
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http://dx.doi.org/10.1002/cbin.10203DOI Listing
March 2014

Silibinin promotes osteoblast differentiation of human bone marrow stromal cells via bone morphogenetic protein signaling.

Eur J Pharmacol 2013 Dec 25;721(1-3):225-30. Epub 2013 Sep 25.

Department of Orthopedic Surgery, The Second Affiliated Hospital of Wenzhou Medical College, 109 Xue Yuan xi Road, Wenzhou 325000, China. Electronic address:

Silibinin is the major active constituent of the natural compound silymarin; several studies suggest that silibinin possesses antihepatotoxic properties and anticancer effects against carcinoma cells. However, no study has yet investigated the effect of silibinin on osteogenic differentiation of human bone marrow stem cells (hBMSCs). The aim of this study was to evaluate the effect of silibinin on osteogenic differentiation of hBMSCs. In this study, the hBMSCs were cultured in an osteogenic medium with 0, 1, 10 or 20 μmol/l silibinin respectively. hBMSCs viability was analyzed by cell number quantification assay and cells osteogenic differentiation was evaluated by alkaline phosphatas (ALP) activity assay, Von Kossa staining and real time-polymerase chain reaction (RT-PCR). We found that silibinin promoted ALP activity in hBMSCs without affecting their proliferation. The mineralization of hBMSCs was enhanced by treatment with silibinin. Silibinin also increased the mRNA expressions of Collagen type I (COL-I), ALP, Osteocalcin (OCN), Osterix, bone morphogenetic protein-2 (BMP-2) and Runt-related transcription factor 2 (RUNX2). The BMP antagonist noggin and its receptor kinase inhibitors dorsomorphin and LDN-193189 attenuated silibinin-promoted ALP activity. Furthermore, BMP-responsive and Runx2-responsive reporters were activated by silibinin treatment. These results indicate that silibinin enhances osteoblast differentiation probably by inducing the expressions of BMPs and activating BMP and RUNX2 pathways. Thus, silibinin may play an important therapeutic role in osteoporosis patients by improving osteogenic differentiation of BMSCs.
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http://dx.doi.org/10.1016/j.ejphar.2013.09.031DOI Listing
December 2013

Piperine inhibits LPS induced expression of inflammatory mediators in RAW 264.7 cells.

Cell Immunol 2013 Sep-Oct;285(1-2):49-54. Epub 2013 Sep 11.

Department of Orthopaedic Surgery, The Second Affiliated Hospital of Wenzhou Medical College, Wenzhou 325000, China. Electronic address:

The aim of the present study was to investigate the effects of piperine on the inflammatory responses to lipopolysaccharide (LPS) in RAW264.7 cells and the signal transduction pathways involved. RAW264.7 cells were pretreated with piperine at 10, 50 or 100 μg/ml and subsequently stimulated with LPS (1 μg/ml) for 24 h. We found that piperine inhibited the production of prostaglandin E2 (PGE2) and nitric oxide (NO) induced by LPS. Piperine significantly decreased LPS-stimulated gene expression and production of tumor necrosis factor-alpha (TNF), inducible NO synthase (iNOS) and COX-2 in RAW264.7 cells. Piperine inhibited the LPS-mediated activation of nuclear factor-kappa B (NF-kappaB) by suppressing the degradation of inhibitor-κB proteins (IκB) and the translocations of p65 subunit of NF-kB from the cytosol to the nucleus. Our results demonstrate the anti-inflammatory activity of piperine in RAW264.7 cells; suggesting that piperine may be a potential agent in the treatment of inflammation.
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http://dx.doi.org/10.1016/j.cellimm.2013.09.001DOI Listing
January 2014

The hepatoprotective effect of fraxetin on carbon tetrachloride induced hepatic fibrosis by antioxidative activities in rats.

Int Immunopharmacol 2013 Nov 27;17(3):543-7. Epub 2013 Aug 27.

Department of Infectious Diseases, the First Affiliated Hospital of Wenzhou Medical College, China.

The aim of the study was to investigate the potentially protective effects of fraxetin on carbon tetrachloride (CCl4) induced oxidative stress and hepatic fibrosis in Sprague-Dawley rats. In this study, rats were divided into five groups, including normal controls, model, silymarin as the positive control, fraxetin 20 mg/kg and fraxetin 50 mg/kg. After 8 weeks, activities of serum alanine aminotransferase (ALT), aspartate aminotransferase (AST) and total bilirubin (TBIL) were checked. The levels of protein carbonyls, thiobarbituric acid-reactive substances (TBARS) and antioxidant enzymes such as catalase, SOD and glutathione peroxidase (GSH-Px) were determined after fraxetin administration. The hydroxyproline levels and histopathologic examinations of hepatocyte fibrosis were also determined. We found that fraxetin at doses of 20 and 50 mg/kg for 8 weeks significantly reduced the levels of TBARS and protein carbonyls compared with CCl4 group. Fraxetin significantly increased the activities of catalase, SOD and GSH-Px in the liver. We also found that fraxetin prevented CCl4 induced hepatic fibrosis by histological observations. These results indicate that fraxetin exhibits potent protective effects against CCl4 induced oxidative stress and hepatic fibrosis.
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http://dx.doi.org/10.1016/j.intimp.2013.08.006DOI Listing
November 2013

Piperine inhibits IL-β induced expression of inflammatory mediators in human osteoarthritis chondrocyte.

Int Immunopharmacol 2013 Oct 6;17(2):293-9. Epub 2013 Jul 6.

Department of Orthopaedic Surgery, The Second Affiliated Hospital of Wenzhou Medical College, Wenzhou, China.

Black pepper (Piper nigrum) is a common remedy in Traditional Chinese Medicine and possesses diverse biological activities including anti-inflammatory properties. Osteoarthritis (OA) is a degenerative joint disease with an inflammatory component that drives the degradation of cartilage extracellular matrix. The present study aimed to assess the effects of piperine, the active phenolic component in black pepper extract, on human OA chondrocytes. In this study, human OA chondrocytes were pretreated with piperine at 10, 50 or 100μg/ml and subsequently stimulated with IL-1β (5ng/ml) for 24h. Production of PGE2 and NO was evaluated by the Griess reaction and an ELISA. Gene expression of MMP-3, MMP-13, iNOS and COX-2 was measured by real-time PCR. MMP-3 and MMP-13 proteins in culture medium were determined using cytokine-specific ELISA. Western immunoblotting was used to analyze the iNOS and COX-2 protein production in the culture medium. The regulation of NF-kB activity and the degradation of IkB were explored using luciferase and Western immunoblotting, respectively. We found that piperine inhibited the production of PGE2 and NO induced by IL-1β. Piperine significantly decreased the IL-1β-stimulated gene expression and production of MMP-3, MMP-13, iNOS and COX-2 in human OA chondrocytes. Piperine inhibited the IL-1β-mediated activation of NF-κB by suppressing the degradation of its inhibitory protein IκBα in the cytoplasm. The present report is first to demonstrate the anti-inflammatory activity of piperine in human OA chondrocytes. Piperine can effectively abrogate the IL-1β-induced over-expression of inflammatory mediators; suggesting that piperine may be a potential agent in the treatment of OA.
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http://dx.doi.org/10.1016/j.intimp.2013.06.025DOI Listing
October 2013

Effects of extracellular calcium on viability and osteogenic differentiation of bone marrow stromal cells in vitro.

Hum Cell 2013 Sep 8;26(3):114-20. Epub 2013 Jun 8.

Trauma Center of the Affiliated Hospital of Hainan Medical College, 31 Long Hua Road, Haikou, 571100, China.

Bone marrow stromal cells (BMSCs) have been extensively used for tissue engineering. However, the effect of Ca(2+) on the viability and osteogenic differentiation of BMSCs has yet to be evaluated. To determine the dose-dependent effect of Ca(2+) on viability and osteogenesis of BMSCs in vitro, BMSCs were cultured in calcium-free DMEM medium supplemented with various concentrations of Ca(2+) (0, 1, 2, 3, 4, and 5 mM) from calcium citrate. Cell viability was analyzed by MTT assay and osteogenic differentiation was evaluated by alkaline phosphatase (ALP) assay, Von Kossa staining, and real-time PCR. Ca(2+) stimulated BMSCs viability in a dose-dependent manner. At slightly higher concentrations (4 and 5 mM) in the culture, Ca(2+) significantly inhibited the activity of ALP on days 7 and 14 (P < 0.01 or P < 0.05), significantly suppressed collagen synthesis (P < 0.01 or P < 0.05), and significantly elevated calcium deposition (P < 0.01) and mRNA levels of osteocalcin (P < 0.01 or P < 0.05) and osteopontin (P < 0.01 or P < 0.05). Therefore, elevated concentrations of extracellular calcium may promote cell viability and late-stage osteogenic differentiation, but may suppress early-stage osteogenic differentiation in BMSCs.
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http://dx.doi.org/10.1007/s13577-012-0041-8DOI Listing
September 2013

SeMet inhibits IL-1β-induced rheumatoid fibroblast-like synoviocytes proliferation and the production of inflammatory mediators.

Biol Trace Elem Res 2013 Jun 17;153(1-3):437-45. Epub 2013 May 17.

Department of Orthopaedic Surgery, The Second Affiliated Hospital of Wenzhou Medical College, 109 Xue Yuan Xi Road, Wenzhou 325000, China.

Previous studies demonstrated that Se has anti-inflammatory activities and that it plays an important role in maintaining normal cartilage metabolism. Nevertheless, little is known about the effects of Se on the production of inflammatory mediators in rheumatoid fibroblast-like synoviocytes (FLSs). The objective of this study was to determine the effects of Se on the interleukin-1β (IL-1β)-induced proliferation of FLSs and production of matrix metalloproteinases (MMPs) and inflammatory mediators by FLSs. In this study, the proliferation of FLSs was assessed using the MTT assay after cultured with/without the presence of IL-1β and SeMet. Human FLSs were pretreated with SeMet (0.5 μM) and subsequently stimulated with IL-1β (5 ng/ml) for 24 h. Production of NO and PGE2 were evaluated by the Griess reaction and ELISA. Gene expression of MMP-3, MMP-13, iNOS, and COX-2 was measured by real-time PCR. MMP-3 and MMP-13 proteins in culture medium were determined using cytokine-specific ELISA. Western immunoblotting was used to analyze the iNOS and COX-2 protein production in the culture medium and the activity of phosphorylation of P38 MAPK pathways. We found that SeMet significantly inhibits IL-1β-induced proliferation of FLSs. SeMet also inhibited the production of PGE2 and NO induced by IL-1β. SeMet significantly decreased IL-1β-stimulated gene expression and production of MMP-3, MMP-13, iNOS, and COX-2 in human FLSs. In addition, we found SeMet partly inhibited the IL-1β-induced activation of p38 MAPK pathways. The present report is first to demonstrate that SeMet inhibits IL-1β-induced expression of MMPs and production of inflammatory factors in cultured FLSs, indicating that SeMet may be a potential agent in the treatment of rheumatoid arthritis.
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http://dx.doi.org/10.1007/s12011-013-9696-6DOI Listing
June 2013

Nicotine-induced chondrogenic differentiation of human bone marrow stromal cells in vitro.

Knee Surg Sports Traumatol Arthrosc 2012 Nov 19;20(11):2329-36. Epub 2012 Jan 19.

Department of Orthopaedic Surgery, The Second Affiliated Hospital of Wenzhou Medical College, 109 Xue Yuan Xi Road, Wenzhou, China.

Purpose: Nicotine has been reported that it has a dose-dependent effect on matrix mineralization by human bone marrow cells. However, there is no relevant research concerning on chondrogenic differentiation potential of bone marrow stromal stem cells (BMSCs) treated with nicotine in vitro. The aims of the study were to examine the effects of nicotine (0, 10(-7), 10(-6) and 10(-5) M) on the proliferation and chondrogenic differentiation of BMSCs from three healthy donors in vitro.

Methods: BMSCs proliferation was analyzed by CCK8 assay and real-time polymerase chain reaction was used to assay the expression of type II collagen, aggrecan, type I collagen and type X collagen. The proteoglycan content was stained by Alcian blue, and the sulfated glycosaminoglycan (sGAG) content of BMSCs was quantified spectrofluorometrically using dimethylmethylene blue.

Results: The cell viability was not significantly impaired until up to a concentration of 10(-5) M nicotine. Nicotine promoted the proliferation and enhanced the expression of type II collagen at the level up to 10(-6) M (P < 0.05). The expression of aggrecan was reduced at the concentration of 10(-5) M nicotine at day 14 (P < 0.05), and there was no significant difference in aggrecan gene expression at 10(-7) and 10(-6) M nicotine levels compared to control group (n.s.). Also the fibroblastic and hypertrophic gene expressions were down-regulated in the chondrogenic medium with 10(-7)-10(-5) M nicotine (P < 0.05).

Conclusion: It was implied that local application of nicotine at an appropriate concentration may be a promising approach for enhancing chondrogenic differentiation capacity of BMSCs in cell-based cartilage tissue engineering. Also these results indicate that nicotine maybe a potentially useful drug for the treatment of Osteoarthritis.
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http://dx.doi.org/10.1007/s00167-012-1890-0DOI Listing
November 2012

Nicotine promotes proliferation and collagen synthesis of chondrocytes isolated from normal human and osteoarthritis patients.

Mol Cell Biochem 2012 Jan 19;359(1-2):263-9. Epub 2011 Aug 19.

Department of Orthopaedic Surgery, The Second Affiliated Hospital of Wenzhou Medical College, Xue Yuan Xi Road, Wenzhou, 325000, China.

The aims of the study were to show the direct effect of nicotine with different concentrations (0, 25, 50, and 100 ng/ml) on chondrocytes isolated from normal human and osteoarthritis patients, respectively. Microscopic observation was performed during the culture with an inverted microscope. Methyl thiazolyl tetrazolium (MTT) assay method was adopted to observe the influence of nicotine on the proliferation of chondrocytes, and real-time PCR and ELISA were used to assay the mRNA and protein expression of type II collagen and aggrecan, respectively. We discovered that the OA chondrocytes were similar to fibroblasts in shape and grow slower than normal chondrocytes. The proliferation of the two kinds of chondrocytes was increased in a concentration-dependent manner and in a time-dependent manner (P<0.05). Also, we found that the mRNA level of type II collagen were upregulated under 25-100 ng/ml nicotine doses both in the two kinds of chondrocytes compared with control. The expression of protein levels of type II collagen were synthesized in line with the increase in mRNA. No effect was observed on aggrecan synthesis with any nicotine dose. We concluded that nicotine has the same effect on both chondrocytes, obtained either from osteoarthritis patients or from normal human, and the positive effect of smoking in OA may relate to the alteration in metabolism of chondrocytes.
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http://dx.doi.org/10.1007/s11010-011-1020-1DOI Listing
January 2012

Effect of lactoferrin on osteogenic differentiation of human adipose stem cells.

Int Orthop 2012 Mar 29;36(3):647-53. Epub 2011 Jun 29.

Department of Orthopaedic Surgery, The Second Affiliated Hospital of Wenzhou Medical College, 109 Xue yuan xi Road, Wenzhou, 325000, China.

Purpose: Many in vitro studies of the analysis of the lactoferrin (LF) effect on cells have been reported. However, no study has yet investigated the effect of LF on osteogenic differentiation of human adipose-derived stem cells (hADSCs). The aim of this study was to evaluate the effect of LF on osteogenic differentiation of human adipose stem cells.

Methods: The hADSCs were cultured in an osteogenic medium with 0, 10, 50 and 100 μg/ml LF, respectively. hADSC proliferation was analysed by Cell Counting Kit-8 (CCK-8) assay, and cell osteogenic differentiation was evaluated by alkaline phosphatase (ALP) activity assay, von Kossa staining and real-time polymerase chain reaction (RT-PCR).

Results: Cell proliferation was significantly increased by LF in a dose-dependent manner from days 4 to 14. Cells cultured with 100 μg/ml LF presented a higher activity compared with the control. The deposition of calcium was increased after the addition of LF. The mRNA expression of type I collagen (COL-I), ALP, osteocalcin (OCN) and RUNX2 increased markedly as a result of LF treatment.

Conclusions: We have shown for the first time that LF could promote the proliferation and osteogenic differentiation of hADSCs, which could be a promising approach for enhancing osteogenic capacity of cell-based construction in bone tissue engineering.
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http://dx.doi.org/10.1007/s00264-011-1303-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3291782PMC
March 2012