Publications by authors named "Zhihe Zhao"

172 Publications

Directional Magnetization Reversal Enables Ultrahigh Energy Density in Gradient Nanostructures.

Adv Mater 2021 Jul 26:e2102800. Epub 2021 Jul 26.

State Key Laboratory of Metastable Materials Science and Technology, Yanshan University, Qinhuangdao, 066004, China.

High-performance ferromagnetic materials are essential for energy conversion and electronic devices. However, the random and nonuniform magnetization reversal in ferromagnetics limits their performance that can be achieved. Here, through both micromagnetism simulations and experiments, a directional magnetization reversal that initiates first from large grains toward smaller ones is discovered by engineering Nd Fe B/α-Fe gradient nanostructures. Such directional magnetization reversal enables a rare combination of high magnetization and large coercivity, thus leading to a record-high energy density (26 MG Oe) for isotropic permanent magnetic materials, which is ≈50% higher than that of its gradient-free counterpart. The unusual magnetization reversal originates from an ordered arrangement of grain sizes in the gradient material, where the large grains have a lower reversal field than that of the smaller ones. These findings open up new opportunities for developing high-performance magnetic materials.
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http://dx.doi.org/10.1002/adma.202102800DOI Listing
July 2021

miR-20a-5p contributes to osteogenic differentiation of human dental pulp stem cells by regulating BAMBI and activating the phosphorylation of Smad5 and p38.

Stem Cell Res Ther 2021 07 22;12(1):421. Epub 2021 Jul 22.

State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, No. 14, 3rd Section, South Renmin Road, Chengdu, 610041, Sichuan, China.

Background: Human dental pulp stem cells (hDPSCs) are the preferable choice of seed cells for craniomaxillofacial bone tissue regeneration. As a member of the miR-17-92 cluster, miR-20a-5p functions as an important regulator during bone remodeling. This study aimed to investigate the roles and mechanisms of miR-20a-5p during osteogenesis of hDPSCs.

Methods: Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) was conducted to determine the expression of miR-20a-5p during osteogenesis of hDPSCs. We interfered with the expression of miR-20a-5p in hDPSCs to clarify the function of miR-20a-5p on osteogenesis both in vitro and vivo. Direct bind sites between miR-20a-5p and BAMBI were confirmed by dual-luciferase reporter assay, and the underlying mechanisms were investigated with cell co-transfections.

Results: The expression of miR-20a-5p was showed to be upregulated during osteogenesis of hDPSCs. Inhibition of miR-20a-5p could weaken the intensity of ALP/ARS staining and downregulate the expression of mRNAs and proteins of osteogenic markers, while overexpression of miR-20a-5p could enhance the intensity of ALP/ARS staining and the expression of osteogenic markers. Both micro-CT reconstruction images and histological results showed that miR-20a-5p could promote the regeneration of calvarial defects. miR-20a-5p directly targeted bone morphogenetic protein and activin membrane-bound inhibitor (BAMBI), and the latter one was an inhibitor of hDPSC osteogenesis. Silencing BAMBI partially reversed the suppression effect of miR-20a-5p knockdown on osteogenesis. Phosphorylation of Smad5 and p38 was decreased when miR-20a-5p was silenced, whereas p-Smad5 and p-p38 were upregulated when miR-20a-5p was overexpressed or BAMBI was silenced.

Conclusions: It is demonstrated that miR-20a-5p functioned as a regulator of BAMBI to activate the phosphorylation of Smad5 and p38 during osteogenic differentiation of hDPSCs.
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http://dx.doi.org/10.1186/s13287-021-02501-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8296686PMC
July 2021

Dental-Derived Mesenchymal Stem Cells: State of the Art.

Front Cell Dev Biol 2021 22;9:654559. Epub 2021 Jun 22.

State Key Laboratory of Oral Diseases, West China School of Stomatology, Sichuan University, Chengdu, China.

Mesenchymal stem cells (MSCs) could be identified in mammalian teeth. Currently, dental-derived MSCs (DMSCs) has become a collective term for all the MSCs isolated from dental pulp, periodontal ligament, dental follicle, apical papilla, and even gingiva. These DMSCs possess similar multipotent potential as bone marrow-derived MSCs, including differentiation into cells that have the characteristics of odontoblasts, cementoblasts, osteoblasts, chondrocytes, myocytes, epithelial cells, neural cells, hepatocytes, and adipocytes. Besides, DMSCs also have powerful immunomodulatory functions, which enable them to orchestrate the surrounding immune microenvironment. These properties enable DMSCs to have a promising approach in injury repair, tissue regeneration, and treatment of various diseases. This review outlines the most recent advances in DMSCs' functions and applications and enlightens how these advances are paving the path for DMSC-based therapies.
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http://dx.doi.org/10.3389/fcell.2021.654559DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8258348PMC
June 2021

Hyperglycemia modulates M1/M2 macrophage polarization via reactive oxygen species overproduction in ligature-induced periodontitis.

J Periodontal Res 2021 Jun 30. Epub 2021 Jun 30.

State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China.

Background And Objective: Periodontitis in diabetic patients is characterized by enhanced inflammation and aggravated tissue damage in comparison with that in non-diabetic counterparts. The progression of periodontal damage under diabetic condition can be partly ascribed to hyperglycemia-induced disturbance between immune activation and inflammation resolution, where macrophages are capable of participating given their plasticity in response to different stimuli. Herein, we aimed to investigate the changes of macrophage polarization in periodontitis under diabetic condition and the underlying mechanism.

Materials And Methods: Type-1 diabetes was induced by the injection of streptozotocin (STZ, 60 mg/kg) in Sprague-Dawley rats. Rats in N-acetyl cysteine (NAC)-treated groups received NAC dissolved in drinking water (200 mg/kg/day). Experimental periodontitis was induced by ligating 3-0 silk around left maxillary second molars for 4 weeks. Alveolar bone destruction was tested by micro-computed tomography and tartrate-resistant acid phosphatase (TRAP) staining. M1/M2 macrophage polarization in periodontal tissue was detected by immunohistochemistry staining. RAW264.7 were cultured in normal glucose (5.5 mM) or high glucose environment (25 mM) with or without NAC (8 mmol/L). LPS (100 ng/ml) and IL-4 (20 ng/ml) were used to induce M1 macrophages and M2 macrophages, respectively. M1/M2 macrophage polarization was detected by qRT-PCR, immunofluorescent staining, and flow cytometry. Reactive oxygen species (ROS) accumulation was detected by fluorogenic probes. RANKL (100 ng/ml) were applied to induce osteoclastogenic differentiation of RAW264.7, and osteoclast formation was examined by TRAP staining.

Results: Rats with diabetes displayed enhanced macrophages infiltration and M1 macrophage polarization in periodontal lesions compared with vehicle-treated rats. Under LPS or IL-4 stimulation, high glucose culture of RAW264.7 elevated ROS level and increased the expression of M1 macrophage markers (iNOS, TNF-α, and IL-6) whereas decreased the expression of M2 macrophage markers (Arg-1 and CD206). Supernatants of high glucose-treated M1/M2 macrophages enhanced osteoclast formation compared to normal glucose-cultured cells. Decreasing ROS level via NAC partially reversed the effect of high glucose on M1/M2 macrophage polarization. Meanwhile, daily intake of NAC in rodent models inhibited M1 macrophage polarization, which subsequently ameliorated alveolar bone loss and decreased osteoclast numbers in periodontitis in diabetic rats.

Conclusion: These findings demonstrated that hyperglycemia could polarize macrophage toward M1 macrophages via overproducing ROS under inflammatory condition, which might take responsibility for aggravated periodontal damage in periodontitis under diabetic condition. Inhibiting M1 macrophages and restoring M2 macrophages by ROS scavenger is hopefully a potential adjunct treatment strategy for diabetic periodontitis.
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http://dx.doi.org/10.1111/jre.12912DOI Listing
June 2021

Bone physiological microenvironment and healing mechanism: Basis for future bone-tissue engineering scaffolds.

Bioact Mater 2021 Nov 22;6(11):4110-4140. Epub 2021 Apr 22.

State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, 610041, PR China.

Bone-tissue defects affect millions of people worldwide. Despite being common treatment approaches, autologous and allogeneic bone grafting have not achieved the ideal therapeutic effect. This has prompted researchers to explore novel bone-regeneration methods. In recent decades, the development of bone tissue engineering (BTE) scaffolds has been leading the forefront of this field. As researchers have provided deep insights into bone physiology and the bone-healing mechanism, various biomimicking and bioinspired BTE scaffolds have been reported. Now it is necessary to review the progress of natural bone physiology and bone healing mechanism, which will provide more valuable enlightenments for researchers in this field. This work details the physiological microenvironment of the natural bone tissue, bone-healing process, and various biomolecules involved therein. Next, according to the bone physiological microenvironment and the delivery of bioactive factors based on the bone-healing mechanism, it elaborates the biomimetic design of a scaffold, highlighting the designing of BTE scaffolds according to bone biology and providing the rationale for designing next-generation BTE scaffolds that conform to natural bone healing and regeneration.
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http://dx.doi.org/10.1016/j.bioactmat.2021.03.043DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8091181PMC
November 2021

PTH/PTHrP in controlled release hydrogel enhances orthodontic tooth movement by regulating periodontal bone remodaling.

J Periodontal Res 2021 Apr 15. Epub 2021 Apr 15.

Department of Orthodontics, State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China.

Objective: This study aimed to evaluate the effects of local application of parathyroid hormone (PTH) or parathyroid hormone-related protein (PTHrP) on osteogenesis and osteoclastogenesis during orthodontic tooth movement (OTM).

Background: Periodontal bone remodeling is the crucial biological process in the OTM that involves both bone resorption and formation, with the former more important as the initiator. PTH or PTHrP both play dual roles in bone remodeling regulation, and the balance may shift to the bone resorption side when they are given continuously, suggesting them as potential candidate medicine for OTM acceleration.

Methods: A total of 40 rats underwent orthodontic mesialization of the maxillary first molars and received no micro-perforation (MOP), or MOP followed by injection of temperature-sensitive hydrogel containing PTH, PTHrP, or normal saline. The rats were sacrificed after 2-week OTM, except for the relapse groups, which had one more week of observation after removal of the force appliances. The amount of tooth movement, rate of relapse after OTM, and effects on the bone remodeling were assessed through micro-computed tomography (μCT) analysis, alkaline phosphatase (ALP) assay, alizarin red staining, tartrate-resistant acid phosphatase (TRAP) staining, immunohistochemistry (IHC) analysis, Western blot (WB), and quantitative real-time polymerase chain reaction (qRT-PCR). The effects of PTHrP on the osteogenic differentiation of human periodontal ligament cells (hPDLCs) were explored in vitro.

Results: The cumulative release of PTH or PTHrP from PECE hydrogels was beyond 75% at 14 days in a sustained manner. After the intervention in vivo, the distance of OTM in the PTH (0.78 ± 0.06 mm) or PTHrP (0.81 ± 0.04 mm) group was significantly larger than that of the MOP only (0.51 ± 0.04 mm) or the no MOP (0.46 ± 0.05 mm) group. Moreover, PTH injection significantly reduced the rate of relapse after OTM (25.7 ± 4.3%) compared to the control (69.6 ± 6.1%). μCT analysis showed decreased BV/TV, BS/BV, and Tb.N, while increased Tb.Sp of alveolar bone in the PTH or PTHrP group. There were also more TRAP-positive osteoclasts in the PTH or PTHrP group with a significantly enhanced ratio of receptor activator of nuclear factor-κB ligand (RANKL)/osteoprotegerin (OPG). The protein expressions of PTH/PTHrP type 1 receptor (PTHR1), alkaline phosphatase (ALP), osteocalcin (OCN), runt-related transcription factor 2 (RUNX2), and β-catenin were significantly increased in the PTH or PTHrP group, as well as the gene expressions of Pth1r, Bglap, and Alpl. There was no significant difference between the effects of PTH and PTHrP. Nevertheless, inhibition of PTHrP on the osteogenic differentiation of hPDLCs was detected in vitro with decreased expression of OCN, RUNX2, COL-1, and ALP.

Conclusion: Local injection of either PTH or PTHrP carried by controlled release PECE hydrogel similarly enhances OTM in rats through regulating periodontal bone remodeling, which deserves further study for potential clinical application.
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http://dx.doi.org/10.1111/jre.12885DOI Listing
April 2021

Non-Coding RNAs Steering the Senescence-Related Progress, Properties, and Application of Mesenchymal Stem Cells.

Front Cell Dev Biol 2021 19;9:650431. Epub 2021 Mar 19.

State Key Laboratory of Oral Diseases and National Clinical Research Center for Oral Diseases, Department of Orthodontics, West China Hospital of Stomatology, Sichuan University, Chengdu, China.

The thirst to postpone and even reverse aging progress has never been quenched after all these decades. Unequivocally, mesenchymal stem cells (MSCs), with extraordinary abilities such as self-renewal and multi-directional differentiation, deserve the limelight in this topic. Though having several affable clinical traits, MSCs going through senescence would, on one hand, contribute to age-related diseases and, on the other hand, lead to compromised or even counterproductive therapeutical outcomes. Notably, increasing evidence suggests that non-coding RNAs (ncRNAs) could invigorate various regulatory processes. With even a slight dip or an uptick of expression, ncRNAs would make a dent in or even overturn cellular fate. Thereby, a systematic illustration of ncRNAs identified so far to steer MSCs during senescence is axiomatically an urgent need. In this review, we introduce the general properties and mechanisms of senescence and its relationship with MSCs and illustrate the ncRNAs playing a role in the cellular senescence of MSCs. It is then followed by the elucidation of ncRNAs embodied in extracellular vesicles connecting senescent MSCs with other cells and diversified processes in and beyond the skeletal system. Last, we provide a glimpse into the clinical methodologies of ncRNA-based therapies in MSC-related fields. Hopefully, the intricate relationship between senescence and MSCs will be revealed one day and our work could be a crucial stepping-stone toward that future.
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http://dx.doi.org/10.3389/fcell.2021.650431DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8017203PMC
March 2021

Dentofacial characteristics and age in association with incisor bony support in adult female patients with bimaxillary dentoalveolar protrusion.

Orthod Craniofac Res 2021 Mar 29. Epub 2021 Mar 29.

State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases, Department of Orthodontics, West China Hospital of Stomatology, Sichuan University, Chengdu, China.

Objective: The aim of this study was to analyse the correlation between incisor alveolar bone thickness (IABT) and dentofacial characteristics or age in adult female patients with bimaxillary dentoalveolar protrusion (BDP). Evaluating the contribution of these characteristics may help to predict the IABT differences in this patient population.

Setting And Sample Population: A retrospective study whose sample comprised 80 pretreatment adult female patients with BDP (mean age 24.6 years).

Materials And Methods: The IABT of the bimaxillary central incisors was measured by cone-beam computed tomography. Among the types of IABT, the apical trabecular bone thickness was measured with a quantitative method. The sagittal skeletal pattern, facial divergence, the incisor inclination angle, and mandibular plane angulation were determined by cephalometric analysis. A backward linear multiple regression was performed to analyse the associations between IABT and these characteristics.

Results: Three dentofacial traits and age were associated with IABT. Patients with increased age and facial divergence tended to have a thinner mandibular incisor bone support, while increased root length was associated with a thicker mandibular incisor apical bone thickness. Increased U1-SN and facial divergence may lead to a thinner maxillary incisor palatal bone, while increased U1-SN resulted in a thicker maxillary incisor labial bone.

Conclusions: The bony support of the incisors is associated with age and dentofacial traits. Increasing age and facial divergence are considered risk factors for alveolar defects in female patients with BDP. In contrast, increased root length is associated with a thicker mandibular incisor apical bone support.
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http://dx.doi.org/10.1111/ocr.12484DOI Listing
March 2021

Effect of photobiomodulation therapy on mini-implant stability: a systematic review and meta-analysis.

Lasers Med Sci 2021 Mar 4. Epub 2021 Mar 4.

State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China.

The study aimed to assess trials investigating the effect of PBMT on mini-implant stability. Electronic searches of seven databases and manual search were conducted up to May 2020. Randomized controlled trials and controlled clinical trials evaluating the effect of PBMT on mini-implant stability were included. The risks of bias of individual studies were performed using ROB 2.0 and ROBINS-I-tool based on different study design. Meta-analysis was conducted to compare mini-implant stability exposed to PBMT with control ones at different time points after implantation. Among the 518 records initially identified, seven studies were included in this study. Six studies investigated low-level laser therapy (LLLT) and one study evaluated light-emitting diode (LED) therapy. Two studies were eligible for meta-analysis, which showed that LLLT significantly improved mini-implant stability 60 days after initial implantation (MD - 3.01, 95% CI range [- 4.68, - 1.35], p = 0.0004). High energy density of LLLT began to show beneficial effect on mini-implant stability as early as 3 days after implantation, while the significant effect of low energy density displayed later than 30 days after insertion. LED therapy could improve mini-implant stability after 2 months post-insertion. In conclusion, PBMT appears to be beneficial in ameliorating mini-implant stability. High energy density of LLLT might exert more rapid effect than low energy density. More high-quality clinical trials are needed to further demonstrate PBMT' effects on orthodontic mini-implants.
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http://dx.doi.org/10.1007/s10103-021-03281-6DOI Listing
March 2021

The effect of N-acetylcysteine on the antibacterial capability and biocompatibility of nano silver-containing orthodontic cement.

Angle Orthod 2021 07;91(4):515-521

Objectives: To determine whether the incorporation of N-acetylcysteine (NAC) improves the antibacterial ability and biocompatibility of nano silver (NAg)-containing orthodontic cement.

Materials And Methods: NAg was synthesized using a sodium citrate reduction method. NAg particles were characterized using transmission electron microscopy and ultraviolet-visible absorption spectra. NAg and NAC were incorporated into a resin-modified glass ionomer cement. Enamel shear bond strength (SBS), antibacterial capability, and cytotoxicity were evaluated.

Results: Incorporating 0.15% NAg and 20% NAC had no adverse effect on the SBS of orthodontic cement (P > .1). Adding NAC into NAg-containing cement greatly reduced the biofilm metabolic activity and lactic acid production (P < .05) and lowered the colony unit-forming counts by approximately 1 log (P < .05). The cell viability against NAg-containing cement was improved by NAC (P < .05).

Conclusions: The incorporation of NAC into NAg-containing cement achieved stronger antibacterial capability and better biocompatibility, without compromising the enamel SBS. The combined use of NAC and NAg is promising to combat caries in orthodontic practice.
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http://dx.doi.org/10.2319/073120-670.1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8259744PMC
July 2021

The vital role of Gli1 mesenchymal stem cells in tissue development and homeostasis.

J Cell Physiol 2021 Sep 2;236(9):6077-6089. Epub 2021 Feb 2.

State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, Department of Periodontics, Department of Orthodontics, West China Hospital of Stomatology, Sichuan University, Chengdu, China.

The hedgehog (Hh) signaling pathway plays an essential role in both tissue development and homeostasis. Glioma-associated oncogene homolog 1 (Gli1) is one of the vital transcriptional factors as well as the direct target gene in the Hh signaling pathway. The cells expressing the Gli1 gene (Gli1 cells) have been identified as mesenchymal stem cells (MSCs) that are responsible for various tissue developments, homeostasis, and injury repair. This review outlines some recent discoveries on the crucial roles of Gli1 MSCs in the development and homeostasis of varieties of hard and soft tissues.
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http://dx.doi.org/10.1002/jcp.30310DOI Listing
September 2021

Extracellular Vesicles in Liquid Biopsies: Potential for Disease Diagnosis.

Biomed Res Int 2021 11;2021:6611244. Epub 2021 Jan 11.

Department of Orthodontics, West China Hospital of Stomatology, State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases, Sichuan University, Chengdu, China.

Liquid biopsy is conducted through minimally invasive or noninvasive procedures, and the resulting material can be subjected to genomic, proteomic, and lipidomic analyses for early diagnosis of cancers and other diseases. Extracellular vesicles (EVs), one kind of promising tool for liquid biopsy, are nanosized bilayer particles that are secreted by all kinds of cells and that carry cargoes such as lipids, proteins, and nucleic acids, protecting them from enzymatic degradation in the extracellular environment. In this review, we provide a comprehensive introduction to the properties and applications of EVs, including their biogenesis, contents, sample collection, isolation, and applications in diagnostics based on liquid biopsy.
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http://dx.doi.org/10.1155/2021/6611244DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7814955PMC
May 2021

Aesthetic evaluation of the labiolingual position of maxillary lateral incisors by orthodontists and laypersons.

BMC Oral Health 2021 01 22;21(1):42. Epub 2021 Jan 22.

State Key Laboratory of Oral Diseases and National Clinical Research Center for Oral Diseases, Department of Orthodontics, West China Hospital of Stomatology, 3rd section of Renmin South Road, Chengdu, 610041, Sichuan Province, China.

Background: The maxillary anterior teeth play a crucial role in smile aesthetics. Previous studies regarding the importance of maxillary lateral incisors for smile aesthetics concentrated on their size, incisor edge level, and inclination, etc. However, the aesthetic effect of lateral incisor movement in the spatial position has not been studied yet. Therefore, the purpose of this study was to explore the influence of the labiolingual position of maxillary lateral incisors on the aesthetic perception of smiles by orthodontists and laypersons, as well as analyze differences in this perception between male and female raters.

Methods: A three-dimensional (3D) dental model was generated from the photograph of a man's smile using iOrtho7.0 software (Time Angel, Wuxi, China). Based on this model, seven images were generated with different labiolingual positions of the maxillary lateral incisors in 0.5 mm increments (+ indicating labial translation, and-indicating lingual translation). The images were evaluated by 86 orthodontists and 161 laypersons using a visual analog scale, with lower scores indicating less attractiveness. Data were analyzed using Student's t test and one-way analysis of variance with post hoc test.

Results: There was no significant difference in smile ratings by males and females. Orthodontists assigned lower scores to all images than laypersons. The smile at + 1.5 mm was considered the least attractive by orthodontists, while smiles at + 1.5 mm and - 1.5 mm were regarded as the least attractive by laypersons. The smile at 0 mm was evaluated as the most attractive by all raters. Laypersons gave different scores to smiles at 0 or - 0.5 mm, but orthodontists did not.

Conclusions: The labiolingual position of maxillary lateral incisors does affect the perception of smile aesthetics. Orthodontists may rate smile aesthetics more critically than laypersons. Therefore, communication and discussion between orthodontists and patients is needed to achieve better therapeutic and aesthetic outcomes.
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http://dx.doi.org/10.1186/s12903-021-01402-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7821676PMC
January 2021

circAKT3 positively regulates osteogenic differentiation of human dental pulp stromal cells via miR-206/CX43 axis.

Stem Cell Res Ther 2020 12 9;11(1):531. Epub 2020 Dec 9.

State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, People's Republic of China.

Background: Human dental pulp stromal cells (hDPSCs) are promising sources of mesenchymal stem cells (MSCs) for bone tissue regeneration. Circular RNAs (circRNAs) have been demonstrated to play critical roles in stem cell osteogenic differentiation. Herein, we aimed to investigate the role of circAKT3 during osteogenesis of hDPSCs and the underlying mechanisms of its function.

Methods: We performed circRNA sequencing to investigate the expression profiles of circular RNAs during osteogenesis of hDPSCs. Quantitative reverse transcription polymerase chain reaction (qRT-PCR) was performed to detect the expression pattern of circAKT3 and miR-206 in hDPSCs during osteogenesis. We knocked down circAKT3 and interfered the expression of miR-206 to verify their regulatory role in hDPSC osteogenesis. We detected hDPSCs mineralization by alkaline phosphatase (ALP) and Alizarin Red S (ARS) staining and used dual-luciferase reporter assay to validate the direct binding between circAKT3 and miR-206. To investigate in vivo mineralization, we performed subcutaneous transplantation in nude mice and used hematoxylin and eosin, Masson's trichrome, and immunohistochemistry staining.

Results: Totally, 86 circRNAs were differentially expressed during hDPSC osteogenesis, in which 29 were downregulated while 57 were upregulated. circAKT3 was upregulated while miR-206 was downregulated during hDPSC osteogenesis. Knockdown of circAKT3 inhibited ALP/ARS staining and expression levels of osteogenic genes. circAKT3 directly interacted with miR-206, and the latter one suppressed osteogenesis of hDPSCs. Silencing miR-206 partially reversed the inhibitory effect of circAKT3 knockdown on osteogenesis. Connexin 43 (CX43), which positively regulates osteogenesis of stem cells, was predicted as a target of miR-206, and overexpression or knockdown of miR-206 could correspondingly decrease and increase the expression of CX43. In vivo study showed knockdown of circAKT3 suppressed the formation of mineralized nodules and expression of osteogenic proteins.

Conclusion: During osteogenesis of hDPSCs, circAKT3 could function as a positive regulator by directly sponging miR-206 and arresting the inhibitive effect of miR-206 on CX43 expression.
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http://dx.doi.org/10.1186/s13287-020-02058-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7726914PMC
December 2020

The functions of mechanosensitive ion channels in tooth and bone tissues.

Cell Signal 2021 02 6;78:109877. Epub 2020 Dec 6.

State Key Laboratory of Oral Diseases, Department of Orthodontics, West China School of Stomatology, Sichuan University, Chengdu, PR China. Electronic address:

Tooth and bone are independent tissues with a close relationship. Both are composed of a highly calcified outer structure and soft inner tissue, and both are constantly under mechanical stress. In particular, the alveolar bone and tooth constitute an occlusion system and suffer from masticatory and occlusal force. Thus, mechanotransduction is a key process in many developmental, physiological and pathological processes in tooth and bone. Mechanosensitive ion channels such as Piezo1 and Piezo2 are important participants in mechanotransduction, but their functions in tooth and bone are poorly understood. This review summarizes our current understanding of mechanosensitive ion channels and their roles in tooth and bone tissues. Research in these areas may shed new light on the regulation of tooth and bone tissues and potential treatments for diseases affecting these tissues.
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http://dx.doi.org/10.1016/j.cellsig.2020.109877DOI Listing
February 2021

Wnt16 signaling promotes osteoblast differentiation of periosteal derived cells in vitro and in vivo.

PeerJ 2020 24;8:e10374. Epub 2020 Nov 24.

Columbia University, Center for Craniofacial Regeneration, New York, NY, United States of America.

Background: Periosteum plays critical roles in de novo bone formation and fracture repair. Wnt16 has been regarded as a key regulator in periosteum bone formation. However, the role of Wnt16 in periosteum derived cells (PDCs) osteogenic differentiation remains unclear. The study goal is to uncover whether and how Wnt16 acts on the osteogenesis of PDCs.

Methods: We detected the variation of Wnt16 mRNA expression in PDCs, which were isolated from mouse femur and identified by flow cytometry, cultured in osteogenic medium for 14 days, then knocked down and over-expressed Wnt16 in PDCs to analysis its effects in osteogenesis. Further, we seeded PDCs (Wnt16 over-expressed/vector) in -tricalcium phosphate cubes, and transplanted this complex into a critical size calvarial defect. Lastly, we used immunofluorescence, Topflash and NFAT luciferase reporter assay to study the possible downstream signaling pathway of Wnt16.

Results: Wnt16 mRNA expression showed an increasing trend in PDCs under osteogenic induction for 14 days. Wnt16 shRNA reduced mRNA expression of Runx2, collage type I (Col-1) and osteocalcin (OCN) after 7 days of osteogenic induction, as well as alizarin red staining intensity after 21days. Wnt16 also increased the mRNA expression of Runx2 and OCN and the protein production of Runx2 and Col-1 after 2 days of osteogenic stimulation. In the orthotopic transplantation assay, more bone volume, trabecula number and less trabecula space were found in Wnt16 over-expressed group. Besides, in the newly formed tissue Brdu positive area was smaller and Col-1 was larger in Wnt16 over-expressed group compared to the control group. Finally, Wnt16 upregulated CTNNB1/-catenin expression and its nuclear translocation in PDCs, also increased Topflash reporter luciferase activity. By contrast, Wnt16 failed to increase NFAT reporter luciferase activity.

Conclusion: Together, Wnt16 plays a positive role in regulating PDCs osteogenesis, and Wnt16 may have a potential use in improving bone regeneration.
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http://dx.doi.org/10.7717/peerj.10374DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7694570PMC
November 2020

Correction to: Treatment of the mandibular shift in an adult woman and the diagnostic value of joint space index: a case report.

Eur J Med Res 2020 Nov 12;25(1):58. Epub 2020 Nov 12.

State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, No. 14, 3rd Section, South Renmin Road, Chengdu, 610041, Sichuan, China.

An amendment to this paper has been published and can be accessed via the original article.
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http://dx.doi.org/10.1186/s40001-020-00457-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7661219PMC
November 2020

Treatment of the mandibular shift in an adult woman and the diagnostic value of joint space index: a case report.

Eur J Med Res 2020 Oct 22;25(1):50. Epub 2020 Oct 22.

State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, No. 14, 3rd Section, South Renmin Road, Chengdu, 610041, Sichuan, China.

Background: Mandibular deviations are common clinical complaints. The orthodontic or orthognathic treatment of mandibular deviations is tricky because a comprehensive diagnosis, especially a functional one, is difficult to make. A inaccurate diagnosis may lead to a compromised and unstable treatment outcome.

Case Presentation: This article describes the diagnosis and treatment of a woman with a mandibular deviation and facial skeletal asymmetry. By eliminating the disharmony of the arch form with elastics and bite turbos, her esthetic and functional outcomes improved. Cone-beam CT (CBCT) and Joint Space Index (JSI) analyses served as the diagnostic approaches and outcome evaluation methods before and after treatment.

Conclusions: A condyle position displacement could be an indication of functional deviation. JSI analysis is a quantitative and convenient choice to compare condyle relative positions.
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http://dx.doi.org/10.1186/s40001-020-00451-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7579934PMC
October 2020

Rapid maxillary expansion, with traditional or novel expander?

Am J Orthod Dentofacial Orthop 2020 06;157(6):734

Chengdu, Sichuan, China.

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http://dx.doi.org/10.1016/j.ajodo.2020.03.007DOI Listing
June 2020

MicroRNAs-containing extracellular vesicles in bone remodeling: An emerging frontier.

Life Sci 2020 Aug 16;254:117809. Epub 2020 May 16.

Department of Temporomandibular Joint, State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, China. Electronic address:

Bone remodeling is a complex and constant process, which is maintained by well-regulated communication among various cells. Extracellular vesicles (EVs) are small vesicles, which could provide a protective environment for the transportation of various functional molecules. It has been shown that EVs could dock with distant and/or neighboring target cells, deliver cargoes to these specific cells and alter their fates. MicroRNAs (miRNAs), single-stranded non-coding RNAs with 22-26 nucleotides, could bind to mRNAs and repress the translation or stimulate the degradation of mRNAs. It is reported that EVs could serve as the mail carriers, which could cargo miRNAs to exchange information between different cells and act through a novel way to regulate signaling pathways during bone remodeling. In this review, we summarize the function of EV-miRNAs in the communication among mesenchymal stem cells (MSCs), osteoblasts, osteoclasts, osteocytes, and myoblasts during bone remodeling, as well as the key signaling molecules which are involved in this process. The roles of EV-miRNAs in sending intercellular messages in the microenvironment of bone remodeling could shed new light on the development of tissue engineering, and provide novel diagnostic markers and therapeutic targets of bone-related diseases.
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http://dx.doi.org/10.1016/j.lfs.2020.117809DOI Listing
August 2020

Effect of clear aligners on oral health-related quality of life: A systematic review.

Orthod Craniofac Res 2020 Nov 13;23(4):363-370. Epub 2020 May 13.

State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China.

Clear aligners have been frequently applied in orthodontic clinic practice. However, its effect on oral health-related quality of life (OHRQoL) compared with fixed appliance treatment (FAT) remains inconclusive. This systematic review aimed to compare the impacts of clear aligner treatment (CAT) with FAT on patients' OHRQoL. Electronic searches of databases (PubMed, Cochrane Database of Systematic Reviews, the Cochrane Central Register of Controlled Trials, Embase, Medline, two Chinese databases and six grey literature databases) were conducted up to July 2019. Randomized controlled trials, controlled clinical trials, cohort studies and cross-sectional studies comparing the impact of CAT and FAT on OHRQoL with validated instruments were included. Extraction of data and assessment of the risk of bias were conducted using ROBINS-I-tool, Newcastle-Ottawa Scale and ROB 2.0 based on study design. Of the 1112 records initially identified, 2 studies were included in this review. One study evaluated OHRQoL at the last debonding appointment, while the other made evaluation at the early stage of treatment. In the aspect of functional dimensions, both studies reported less eating disturbance in CAT patients than FAT ones. Based on currently limited information, the effect of CAT on the overall OHRQoL compared to FTA was still inconclusive. In individual dimensions, however, weak evidence supported that CAT might cause less eating disturbance than FAT. More high-quality clinical trials using validated OHRQoL instruments are needed to draw more reliable conclusions in the effect of CAT and FAT on OHRQoL.
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http://dx.doi.org/10.1111/ocr.12382DOI Listing
November 2020

Photopolymerizable Hydrogel-Encapsulated Fibromodulin-Reprogrammed Cells for Muscle Regeneration.

Tissue Eng Part A 2020 10 2;26(19-20):1112-1122. Epub 2020 Jun 2.

Division of Growth and Development, Section of Orthodontics, School of Dentistry, Dental and Craniofacial Research Institute, University of California, Los Angeles, Los Angeles, California, USA.

A central challenge in tissue engineering is obtaining a suitable cell type with a capable delivery vehicle to replace or repair damaged or diseased tissues with tissue mimics. Notably, for skeletal muscle tissue engineering, given the inadequate availability and regenerative capability of endogenous myogenic progenitor cells as well as the tumorigenic risks presented by the currently available pluri- and multipotent stem cells, seeking a safe regenerative cell source is urgently demanded. To conquer this problem, we previously established a novel reprogramming technology that can generate multipotent cells from dermal fibroblasts using a single protein, fibromodulin (FMOD). The yield FMOD-reprogrammed (FReP) cells exhibit exceeding myogenic capability without tumorigenic risk, making them a promising and safe cell source for skeletal muscle establishment. In addition to using the optimal cell for implantation, it is equally essential to maintain cellular localization and retention in the recipient tissue environment for critical-sized muscle tissue establishment. In this study, we demonstrate that the photopolymerizable methacrylated glycol chitosan (MeGC)/type I collagen (ColI)-hydrogel provides a desirable microenvironment for encapsulated FReP cell survival, spreading, extension, and formation of myotubes in the hydrogel three-dimensionally , without undesired osteogenic, chondrogenic, or tenogenic differentiation. Furthermore, gene profiling revealed a → → → → cassette elevation in the encapsulated FReP cells during myogenic differentiation, which is similar to that of the predominant driver of endogenous skeletal muscle regeneration, satellite cells. These findings constitute the evidence that the FReP cell-MeGC/ColI-hydrogel construct is a promising tissue engineering mimic for skeletal muscle generation , and thus possesses the extraordinary potential for further validation.
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http://dx.doi.org/10.1089/ten.TEA.2020.0026DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7580647PMC
October 2020

Orthodontic incisor retraction caused changes in the soft tissue chin area: a retrospective study.

BMC Oral Health 2020 04 15;20(1):108. Epub 2020 Apr 15.

State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, Department of Orthodontics, West China Hospital of Stomatology, Sichuan University, 14 Renmin South Road Third Section, Chengdu, 610041, China.

Background: To investigate the area and morphological changes around the soft tissue chin after orthodontic incisor retraction.

Methods: Fifty-nine female adults with bimaxillary protrusion requiring extraction of four premolars were included in the study. Cephalograms were taken before (T0) and after (T1) orthodontic treatment. The soft tissue changes, including the area, thickness and morphology were measured. Paired-t tests were performed for statistical comparisons. Pearson correlation analyses and backward multivariate regression analyses were used to identify the relationship between the soft tissue changes and incisor retraction.

Results: Following the incisor retractions (5.35 ± 1.79 mm and 4.42 ± 1.62 mm for the upper and lower, respectively), there was a significant increase in the soft tissue thickness of L1c-LL (0.64 ± 1.67 mm, P = 0.025) and Pog-Pog' (0.44 ± 1.10 mm, P = 0.022), and a significant decrease in the soft tissue thickness of B-B' (1.21 ± 1.34 mm, P <  0.01). Changes in the area of soft tissue chin and lower lip were not statistically significant (P > 0.05). Pearson coefficient between the thickness changes of B-B' and the retraction of lower incisors was - 0.376. The multiple correlations between the soft tissue thickness changes and incisor retractions were Y = 1.02-0.42a + 0.42b for L1c-LL, and Y = 0.17-0.31b for B-B'.

Conclusions: The orthodontic incisor retraction could cause soft tissue thickness changes (i.e. an increase in L1c-LL and Pog-Pog' and a decrease in B-B') without area changes.
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http://dx.doi.org/10.1186/s12903-020-01099-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7160892PMC
April 2020

Mechanotransduction pathways in the regulation of cartilage chondrocyte homoeostasis.

J Cell Mol Med 2020 05 1;24(10):5408-5419. Epub 2020 Apr 1.

State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China.

Mechanical stress plays a critical role in cartilage development and homoeostasis. Chondrocytes are surrounded by a narrow pericellular matrix (PCM), which absorbs dynamic and static forces and transmits them to the chondrocyte surface. Recent studies have demonstrated that molecular components, including perlecan, collagen and hyaluronan, provide distinct physical properties for the PCM and maintain the essential microenvironment of chondrocytes. These physical signals are sensed by receptors and molecules located in the cell membrane, such as Ca channels, the primary cilium and integrins, and a series of downstream molecular pathways are involved in mechanotransduction in cartilage. All mechanoreceptors convert outside signals into chemical and biological signals, which then regulate transcription in chondrocytes in response to mechanical stresses. This review highlights recent progress and focuses on the function of the PCM and cell surface molecules in chondrocyte mechanotransduction. Emerging understanding of the cellular and molecular mechanisms that regulate mechanotransduction will provide new insights into osteoarthritis pathogenesis and precision strategies that could be used in its treatment.
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http://dx.doi.org/10.1111/jcmm.15204DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7214151PMC
May 2020

DNA methylation of noncoding RNAs: new insights into osteogenesis and common bone diseases.

Stem Cell Res Ther 2020 03 6;11(1):109. Epub 2020 Mar 6.

State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan, China.

Bone diseases such as osteoarthritis, osteoporosis, and bone tumor present a severe public health problem. Osteogenic differentiation is a complex process associated with the differentiation of different cells, which could regulate transcription factors, cytokines, many signaling pathways, noncoding RNAs (ncRNAs), and epigenetic modulation. DNA methylation is a kind of stable epigenetic alterations in CpG islands without DNA sequence changes and is involved in cancer and other diseases, including bone development and homeostasis. ncRNAs can perform their crucial biological functions at the RNA level, and many findings have demonstrated essential functions of ncRNAs in osteogenic differentiation. In this review, we highlight current researches in DNA methylation of two relevant ncRNAs, including microRNAs and long noncoding RNAs, in the initiation and progression of osteogenesis and bone diseases.
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http://dx.doi.org/10.1186/s13287-020-01625-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7060611PMC
March 2020

microRNA expression profiles and the potential competing endogenous RNA networks in NELL-1-induced human adipose-derived stem cell osteogenic differentiation.

J Cell Biochem 2020 11 17;121(11):4623-4641. Epub 2020 Feb 17.

State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases, Department of Orthodontics, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan, China.

Studies have indicated that Nel-like molecule-1 (NELL-1) was an osteoblast-specific cytokine and some specific microRNAs (miRNAs) could serve as competing endogenous RNA (ceRNA) to partake in osteogenic differentiation of human adipose-derived stem cells (hASCs). The aim of this study was to explore the potential functional mechanisms of recombinant human NELL-1 protein (rhNELL-1) during hASCs osteogenic differentiation. rhNELL-1 was added to osteogenic medium to activate osteogenic differentiation of hASCs. High-throughput RNA sequencing (RNA-Seq) was performed and validated by real-time quantitative polymerase chain reaction. Gene ontology functional annotation and Kyoto Encyclopedia of Genes and Genomes pathway analysis were performed to detect the functions of differentially expressed miRNAs and genes. Coding-noncoding gene co-expression network and ceRNA networks were constructed to predict the potential regulatory role of miRNAs. A total of 1010 differentially expressed miRNAs and 1762 differentially expressed messenger RNAs (mRNAs) were detected. miRNA-370-3p, bone morphogenetic protein 2 (BMP2), and parathyroid hormone like hormone (PTHLH) were differentially expressed during NELL-1-induced osteogenesis. Bioinformatic analyses demonstrated that these differentially expressed miRNAs and mRNAs enriched in Rap1 signaling pathway, PI3K-Akt signaling pathway, p53 signaling pathway, Glucagon signaling pathway, and hypoxia-inducible factor-1 signaling pathway, which were important pathways related to osteogenic differentiation. In addition, miRNA-370-3p and has-miR-485-5p were predicted to interact with circ0001543, circ0002405, and ENST00000570267 in ceRNA networks. Based on the gain or loss of functional experiments by transfection, the results showed that miR-370-3p was a key regulator in osteogenic differentiation by targeting BMP2 and disturbing the expression of PTHLH, and participated in NELL-1-stimulated osteogenesis. The present study provided the primary data and evidence for further exploration on the roles of miRNAs and ceRNAs during NELL-1-induced ossification of hASCs.
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http://dx.doi.org/10.1002/jcb.29695DOI Listing
November 2020

Long noncoding RNA expression profiles during the NEL-like 1 protein-induced osteogenic differentiation.

J Cell Physiol 2020 09 27;235(9):6010-6022. Epub 2020 Jan 27.

State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China.

Long noncoding RNAs (lncRNAs) are important modulators of mesenchymal stem cells (MSCs) in cellular differentiation. However, the regulatory mechanisms of lncRNAs in NEL-like 1 (NELL-1)-induced osteogenic differentiation of human adipose-derived stem cells remain elusive. Expression profiles of lncRNAs and messenger RNAs during NELL-1-induced osteogenesis were obtained using high-throughput sequencing. Gene Ontology, Kyoto Encyclopedia of Genes and Genomes pathway analysis, and gene coexpression networks were performed. We identified 323 statistically differentially expressed lncRNAs during osteogenesis and NELL-1-induced osteogenesis, and three lncRNAs (ENST00000602964, ENST00000326734, and TCONS_00006792) were identified as core regulators. Hedgehog pathway markers, including IHH and GLI1, were downregulated, while the antagonists of this pathway (GLI3 and HHIP) were upregulated during NELL-1-induced osteogenesis. In this process, the antagonist of Wnt, SFRP1, was downregulated. According to the analysis, we speculated that lncRNAs played important roles in NELL-1-induced osteogenesis via the crosstalk between Hedgehog and Wnt pathways.
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http://dx.doi.org/10.1002/jcp.29526DOI Listing
September 2020

Mitochondrial DNA haplogroups participate in osteoarthritis: current evidence based on a meta-analysis.

Clin Rheumatol 2020 Apr 3;39(4):1027-1037. Epub 2020 Jan 3.

State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, No. 14, 3rd section, South Renmin Road, Chengdu, 610041, Sichuan, China.

Mitochondrial genes' variants encoded in both the nuclear and mitochondrial genomes can disrupt mitochondrial function, resulting in losing of cartilage and generating osteoarthritis (OA). However, the association between mtDNA haplogroups and OA still lacks strength evidence supporting. The aim of this meta-analysis is to assess the role of mtDNA haplogroups in speculating the pathogenesis and progression of OA. PubMed, Embase, the Cochrane Central Register of Controlled Trials, and World Health Organization clinical trials' registry center were searched to identify relevant studies up to the end of March 2019. Inclusion citations required a case-control or cohort study to demonstrate the association between mtDNA haplogroups and OA's prevalence or progression. Title, abstract, and full-text screening were sequentially assessed by three reviewers. Data were analyzed using STATA. Besides, publication bias and meta-regression analysis were conducted to explore potential heterogeneities. We collected results from 7 articles. The cluster TJ cases showed a lower proportion in OA cases (RR = 0.83, 95% CI 0.72, 0.96). However, there is no evidence that revealed this kind of impact originated from neither type J nor type T individually. Besides, the type B and G analyses among Asian populations also elucidated a negative association. Moreover, the cluster TJ of mtDNA haplogroups revealed a lower cumulative probability of radiographic OA progression (ES = 0.77, 95% CI 0.63, 0.94), which was contributed by type T (ES = 0.61, 95% CI 0.45, 0.82).The mtDNA haplogroups do have impacts on the prevalence and progression of OA. Cluster TJ could help reduce the prevalence and slow down the radiographic changes; however, the impacts came from type J and type T, respectively.
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http://dx.doi.org/10.1007/s10067-019-04890-xDOI Listing
April 2020

Risk of Bias and Its Impact on Intervention Effect Estimates of Randomized Controlled Trials in Endodontics.

J Endod 2020 Jan;46(1):12-18

State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China. Electronic address:

Introduction: The aims of this study were to evaluate the methodological quality of randomized controlled trials (RCTs) recently published in endodontics and to investigate the influences of methodological characteristics on the magnitude of treatment effects.

Methods: PubMed was searched for RCTs published from October 2013 to October 2018 in 3 leading endodontic journals. The methodological quality of the included studies was determined by using the Cochrane Collaboration risk of bias (RoB) tool. The estimates of intervention effects were expressed or calculated as odds ratios and the standardized mean difference for binary and continuous outcomes, respectively. Meta-regression analyses and Monte Carlo permutation tests were performed to identify the association between RoB and intervention effect estimates.

Results: A total of 121 RCTs were identified as eligible for the current study. For both the studies with binary and continuous outcome measures, the domain of blinding of participants and personnel had the highest percentage of high RoB. For binary outcomes, methodological deficiencies in allocation concealment tended to produce exaggerated treatment effects. For continuous outcomes, risk regarding blinding of participants and personnel and incomplete outcome data were more likely to provide overestimated trial results.

Conclusions: The methodological quality of RCTs within endodontics is suboptimal, and these methodological deficiencies could exaggerate intervention effect estimates in endodontic RCTs. Better trial methodology and more explicit reporting are needed to improve the reliability of evidence in endodontic RCTs.
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http://dx.doi.org/10.1016/j.joen.2019.10.016DOI Listing
January 2020

The roles of circRFWD2 and circINO80 during NELL-1-induced osteogenesis.

J Cell Mol Med 2019 12 21;23(12):8432-8441. Epub 2019 Oct 21.

State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China.

Bone defects caused heavy social and economic burdens worldwide. Nel-like molecule, type 1 (NELL-1) could enhance the osteogenesis and the repairment of bone defects, while the specific mechanism remains to be elucidated. Circular RNAs (circRNAs) have been found to play critical roles in the tissue development and serve as biomarkers for various diseases. However, it remains unclear that the expression patterns of circRNAs and the roles of them played in recombinant NELL-1-induced osteogenesis of human adipose-derived stem cells (hASCs). In this study, we performed RNA-sequencing to investigate the expression profiles of circRNAs in recombinant NELL-1-induced osteogenic differentiation and identified two key circRNAs, namely circRFWD2 and circINO80. These two circRNAs were confirmed to be up-regulated during recombinant NELL-1-induced osteogenesis, and knockdown of them affected the positive effect of NELL-1 on osteogenesis. CircRFWD2 and circINO80 could interact with hsa-miR-6817-5p, which could inhibit the osteogenesis. Silencing hsa-miR-6817-5p could partially reverse the negative effect of si-circRFWD2 and si-circINO80 on the osteogenesis. Therefore, circRFWD2 and circINO80 could regulate the expression of hsa-miR-6817-5p and influence the recombinant NELL-1-induced osteogenic differentiation of hASCs. It opens a new window to better understanding the effects of NELL-1 on the osteogenic differentiation of hASCs and provides potential molecular targets and novel methods for bone regeneration efficiently and safely.
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http://dx.doi.org/10.1111/jcmm.14726DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6850935PMC
December 2019
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