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1.
BMC Musculoskelet Disord ; 25(1): 336, 2024 Apr 26.
Article in English | MEDLINE | ID: mdl-38671454

ABSTRACT

BACKGROUND: An optimized fit of the tibial component to the resection platform and correct rotational alignment are critical for successful total knee arthroplasty (TKA). However, there remains controversy regarding the superiority of symmetric tibial component versus asymmetric tibial component. The objective of this systematic review and meta-analysis was to evaluate the current evidence for comparing the coverage and rotation of asymmetrical and symmetrical tibial component. METHODS: We searched potentially relevant studies form PubMed, Web of science, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), and China National Knowledge Infrastructure (CNKI), up to 1 March 2023. Data extraction and quality assessment were performed by two independent reviewers. Meta-analysis was conducted using Review Manager 5.4. RESULTS: Sixteen articles were identified. Compared to symmetric tibial component, asymmetric tibial component increased the coverage of the proximal tibial cut surface (MD, -2.87; 95%CI, -3.45 to -2.28; P < 0.00001), improved the prevalence of tibial baseplate underhang (OR, 0.16; 95%CI, 0.07 to 0.33; P < 0.00001) and malrotation (OR, 0.13; 95%CI, 0.02 to 0.90; P = 0.04), and reduced the degree of tibial component rotation (MD, -3.11; 95%CI, -5.76 to -0.47; P = 0.02). But there was no statistical significance for improving tibial baseplate overhang (OR, 0.58; 95%CI, 0.08 to 3.97; P = 0.58). Additionally, no revision had occurred for the two tibial components in the included studies. CONCLUSION: The current evidence shows asymmetric tibial component offer advantages in terms of coverage and rotation compared with symmetric tibial component in TKA.


Subject(s)
Arthroplasty, Replacement, Knee , Knee Joint , Knee Prosthesis , Tibia , Humans , Arthroplasty, Replacement, Knee/methods , Arthroplasty, Replacement, Knee/instrumentation , Tibia/surgery , Knee Joint/surgery , Rotation , Prosthesis Design , Treatment Outcome , Osteoarthritis, Knee/surgery , Range of Motion, Articular
3.
Front Bioeng Biotechnol ; 10: 916330, 2022.
Article in English | MEDLINE | ID: mdl-35721849

ABSTRACT

Jaw defects are common in oral and maxillofacial diseases and require surgical repair in extreme cases. Given the limitations in availability and efficacy of autologous bone grafts or allografts, great effort has been made in finding suitable, biocompatible, and effective artificial bone materials. Considering the key role of inflammation in bone resorption, we sought to identify a polypeptide with anti-inflammatory and bone-promoting effects. Rat bone marrow-derived mesenchymal cells (BMSCs) were treated with lipopolysaccharide (LPS) to induce an inflammatory environment, and 1,538 differentially abundant polypeptides were identified using mass spectrometry. Based on mass spectrometry signal intensity, multiple of difference, and structural stability, PAP was screened out as the polypeptide with the lowest abundance in the inflammatory condition. PAP showed no cytotoxicity to BMSCs with increasing concentrations. PAP (10 µM) also increased alkaline phosphatase activity and mRNA expression of Ocn, Bmp2, and Runx2 in a concentration-dependent manner, which confirmed that it can promote osteogenic induction of rat BMSCs. Moreover, PAP reduced LPS-induced expression of inflammatory cytokines (TNF-α, IL-1ß, IL-6) and reactive oxygen species and inhibited polarization of RAW 264.7 macrophages to the inflammatory type. Finally, a skull defect mouse model was established, and mice were injected with LPS and/or PAP. Micro-CT, histological analysis, and immunohistochemical staining showed that PAP significantly reduced the number of LPS-induced bone resorption pits and maintained bone integrity. Overall, the polypeptide PAP screened using LPS stimulation of BMSCs is not cytotoxic and can inhibit the inflammatory reaction process to promote osteogenesis. This study thus provides a basis for development of PAP as a new osteogenic material in the repair of jaw defects.

4.
RSC Adv ; 11(26): 15729-15737, 2021 Apr 26.
Article in English | MEDLINE | ID: mdl-35481171

ABSTRACT

2,3-Dimethylindole (2,3-DMID), a candidate with a hydrogen storage capacity of 5.23 wt%, was studied as a new liquid organic hydrogen carrier (LOHC) in detail in this report. Hydrogenation of 2,3-DMID was conducted over 5 wt% Ru/Al2O3 by investigating the influences of temperature and hydrogen pressure. 100% of fully hydrogenated product, 8H-2,3-DMID can be achieved at 190 °C and 7 MPa in 4 h. Dehydrogenation of 8H-2,3-DMID was performed over 5 wt% Pd/Al2O3 at 180-210 °C and 101 kPa. It is found that dehydrogenation of 8H-2,3-DMID followed first order kinetics with an apparent activation energy of 39.6 kJ mol-1. The structures of intermediates produced in the 8H-2,3-DMID dehydrogenation process were analyzed by DFT calculations.

5.
Front Oncol ; 10: 583682, 2020.
Article in English | MEDLINE | ID: mdl-33363013

ABSTRACT

Circular RNAs (circRNAs) contain microRNA (miRNA)-specific binding sites and can function as miRNA sponges to regulate gene expression by suppressing the inhibitory effect of miRNAs on their target genes. MiR-21-5p has been reported to be involved in the development of head and neck squamous cell carcinoma (HNSCC) and plays an important role in the activation of epithelial-mesenchymal transition (EMT). However, the upstream regulatory mechanism and downstream targets of miR-21-5p in tumor cells remain unknown. CircRNA_ACAP2 inhibits the function of miR-21-5p by binding to its specific binding sites in HNSCC cells. Overexpression of CircRNA_ACAP2 inhibits the proliferation and migration of HNSCC cells, while downregulation of CircRNA_ACAP2 has the opposite effect. STAT3 is a direct target gene of miR-21-5p and a transcription factor of ZEB1. We demonstrate that CircRNA_ACAP2 functions as a tumor suppressor gene in HNSCC and that its function is regulated via the miR-21-5p/STAT3 signaling axis.

6.
Front Pharmacol ; 11: 527744, 2020.
Article in English | MEDLINE | ID: mdl-33041790

ABSTRACT

The purpose of this study was to elucidate the role of the circadian gene Bmal1 in human cartilage and its crosstalk with the MAPK/ERK signaling pathway in temporomandibular joint osteoarthritis (TMJ-OA). We verified the periodical variation of the circadian gene Bmal1 and then established a modified multiple platform method (MMPM) to induce circadian rhythm disturbance leading to TMJ-OA. IL-6, p-ERK, and Bmal1 mRNA and protein expression levels were assessed by real-time RT-PCR and immunohistochemistry. Chondrocytes were treated with an ERK inhibitor (U0126), siRNA and plasmid targeting Bmal1 under IL-6 simulation; then, the cells were subjected to Western blotting to analyze the relationship between Bmal1 and the MAPK/ERK pathway. We found that sleep rhythm disturbance can downregulate the circadian gene BMAL-1 and improve phosphorylated ERK (p-ERK) and IL-6 levels. Furthermore, Bmal1 siRNA transfection was sufficient to improve the p-ERK level and aggravate OA-like gene expression changes under IL-6 stimulation. Bmal1 overexpression relieved the alterations induced by IL-6, which was consistent with the effect of U0126 (an ERK inhibitor). However, we also found that BMAL1 upregulation can decrease ERK phosphorylation, whereas ERK downregulation did not change BMAL1 expression. Collectively, this study provides new insight into the regulatory mechanism that links chondrocyte BMAL1 to cartilage maintenance and repair in TMJ-OA via the MAPK/ERK pathway and suggests that circadian rhythm disruption is a risk factor for TMJ-OA.

7.
Arthritis Res Ther ; 22(1): 99, 2020 05 01.
Article in English | MEDLINE | ID: mdl-32357909

ABSTRACT

BACKGROUND: Due to the lack of research on the pathological mechanism of temporomandibular joint osteoarthritis (TMJOA), there are few effective treatment measures in the clinic. In recent years, microRNAs (miRs) have been demonstrated to play an important role in the pathogenesis of osteoarthritis (OA) by regulating a variety of target genes, and the latest evidence shows that miR-21-5p is specifically overexpressed in OA. The purpose of this project was to clarify whether miR-21-5p can regulate the TMJOA process by targeting Spry1. METHODS: TMJOA was induced by a unilateral anterior crossbite (UAC) model, and the effect of miR-21-5p knockout on TMJOA was evaluated by toluidine blue (TB), immunohistochemical (IHC) staining, Western blotting (WB) and RT-qPCR. Primary mouse condylar chondrocytes (MCCs) were isolated, cultured and transfected with a series of mimics, inhibitors, siRNA-Spry1 or cDNA Spry1. WB, RT-qPCR, IHC and TB were used to detect the effect of miR-21-5p and its target gene Spry1 on the expression of MMP-13, VEGF and p-ERK1/2 in TMJOA. The effect of miR-21-5p on angiogenesis was evaluated by chick embryo chorioallantoic membrane (CAM) assay and WB. RESULTS: In the UAC model, the cartilage thickness and extracellular matrix of miR-21-5p knockout mice were less damaged, and miR-21-5p and UAC model were shown to affect the expression of Spry1, IL-1ß, MMP-13, and VEGF. Luciferase experiments confirmed that Spry1 was the direct target of miR-21-5p. The expression levels of Spry1, MMP-13, VEGF and p-ERK1/2 in MCCs transfected with miR-21-5p mimic were higher than those in the inhibitor group. Under the simulated inflammatory environment of IL-1ß, the expression levels of MMP-13, VEGF and p-ERK1/2 were positively correlated with miR-21-5p, while Spry1 was negatively correlated with miR-21-5p. Inhibition of miR-21-5p expression and overexpression of Spry1 enhanced the inhibition of MMP-13, VEGF and p-ERK1/2 expression. MiR-21-5p had a significant role in promoting angiogenesis in the chick embryo CAM assay, and this role was clearly mediated by the ERK-MAPK signalling pathway. CONCLUSION: This study verified that miR-21-5p can promote the process of TMJOA by targeting Spry1, which provides a new direction for future research on the treatment of this disease.


Subject(s)
Adaptor Proteins, Signal Transducing/genetics , Extracellular Matrix/pathology , Membrane Proteins/genetics , MicroRNAs/genetics , Neovascularization, Pathologic/genetics , Osteoarthritis , Temporomandibular Joint/physiopathology , Animals , Cells, Cultured , Chick Embryo , Chondrocytes , Mice , Mice, Knockout , Osteoarthritis/genetics
8.
RSC Adv ; 10(19): 11039-11045, 2020 Mar 16.
Article in English | MEDLINE | ID: mdl-35495331

ABSTRACT

The competitive adsorption of 8-methylquinoline (8-MQL) and partially hydrogenated product, 4H-8-MQL, was studied by performing a combination of experiments and first-principles calculations over a selected Ru catalyst. A series of hydrogenation reactions were conducted with 8-MQL and 4H-8-MQL as initial reactants, respectively. 8-MQL exhibits stronger adsorption on catalyst surface active sites compared with 4H-8-MQL and the massive adsorption of 8-MQL hampers the further adsorption of 4H-8-MQL. The effects of temperature, pressure and solvent on the selectivity in 8-MQL hydrogenation were investigated as well. Full hydrogenation of 8-MQL to 10H-8-MQL was achieved within 120 min when the catalyst dosage increased from 5 wt% to 7 wt% under 160 °C and a hydrogen pressure of 7 MPa. The electronic charge of the N-heteroatom in 8-MQL and 4H-8-MQL was analyzed and the adsorption geometries of 8-MQL and 4H-8-MQL on the Ru(001) surface were optimized by DFT calculations to explain the competitive adsorption behaviors of 8-MQL and 4H-8-MQL.

9.
Front Pharmacol ; 10: 1290, 2019.
Article in English | MEDLINE | ID: mdl-31780931

ABSTRACT

The main causes of cartilage destruction during temporomandibular joint osteoarthritis (TMJOA) are extracellular matrix degradation and angiogenesis, accompanied by an increased level of matrix-degrading enzymes and proangiogenic factors. Interleukin 6 and extracellular signal-regulated kinase (ERK) signaling pathways may play a critical role in these two processes simultaneously, but researchers have not clearly determined the mechanism. We hypothesized that estrogen-related receptor γ (ERRγ) is involved in both cartilage degeneration and angiogenesis in TMJOA. The interactions between ERRγ and the Mmp9 and Vegfa promoter regions were investigated using a chromatin immunoprecipitation (ChIP) assay. A chick embryo chorioallantoic membrane (CAM) assay was performed to investigate the inhibitory effects of U0126 and GSK5182 on angiogenesis. Western blotting, reverse transcription-quantitative PCR (RT-qPCR), immunofluorescence staining, toluidine blue staining, and transfection with cDNAs or small interfering RNAs (siRNAs) were performed on primary mandibular condylar chondrocytes (MCCs). Unilateral anterior crossbite-induced TMJOA models were established in rats, and Western blotting, RT-qPCR, immunohistochemistry, and Safranin O-Fast Green staining were performed to evaluate changes in vivo. ERK1/2 activated matrix metalloproteinase 9 (MMP9) and vascular endothelial growth factor A (VEGFA), which are involved in cartilage destruction, through ERRγ. Based on the ChIP assay results, ERRγ directly activated the transcription of the Mmp9 and Vegfa genes. In chick embryo CAM models, U0126 and GSK5182 significantly inhibited angiogenesis. In conclusion, ERRγ is a downstream transcription factor of ERK1/2, and its upregulation leads to extracellular matrix degradation and angiogenesis in TMJOA. This study identified a common factor between inflammation and vascularization in OA as well as a new therapeutic target for OA: ERRγ.

10.
Br J Oral Maxillofac Surg ; 57(10): 977-984, 2019 12.
Article in English | MEDLINE | ID: mdl-31540844

ABSTRACT

The purpose of this study was to assess the influence of two suture methods on the postoperative complications of extraction of mandibular third molars (M3M). We searched the MEDLINE (PubMed), Cochrane Library, and Web of Science databases until 18 May 2018 for randomised controlled trials (RCT) that evaluated the influence of any suture techniques on postoperative complications after the removal of impacted M3M. Pain, facial swelling, and trismus were measured for both the early stage (2-3 days) and late stage (5-7 days) after extraction. We identified 655 records, of which five were assessed for eligibility. All trials included had a moderate risk of bias. The analysis showed that the patients whose wounds had been closed primarily had significantly more pain than those whose wounds were closed secondarily (a wedge of mucosa) during the early stage (standardised mean difference (SMD), -0.49; 95% CI -0.71 to -0.27; P<0.0001) and the late stage (SMD -0.36; 95% CI -0.54 to -0.19; P<0.0001) after the removal of impacted M3M. Patients whose wounds were closed secondarily had less swelling (mm) at the postoperative early stage (SMD -1.12; 95% CI -1.57 to -0.66; P<0.00001) and late stage (SMD -0.51; 95% CI -0.68 to -0.33; P<0.00001). There was more trismus in the primary closure group than in the secondary group during both stages. Our findings suggest that secondary closure causes less pain, facial swelling, and trismus in both early and late stages of surgical removal of impacted M3M, and therefore it improves the quality of life by reducing postoperative discomfort.


Subject(s)
Molar, Third , Tooth Extraction , Tooth, Impacted , Edema , Humans , Pain, Postoperative , Postoperative Complications , Quality of Life , Trismus
11.
J Oral Maxillofac Surg ; 77(8): 1566-1574, 2019 Aug.
Article in English | MEDLINE | ID: mdl-30986376

ABSTRACT

PURPOSE: The purpose of this study was to evaluate whether bromelain can decrease trismus, pain, and facial swelling in patients undergoing impacted third molar surgery. MATERIALS AND METHODS: Three databases were searched to identify relevant studies through November 1, 2017. Randomized controlled trials (RCTs) that compared the effect of bromelain versus placebo after mandibular third molar surgery were included. The main outcome measures, pain, facial swelling, and trismus, were assessed in the early stage (2 to 3 days) and the late stage (7 days) after surgery. Standardized mean differences (SMDs) and weighted mean differences (WMDs) were calculated using fixed-effect models. All statistical analyses were implemented using Review Manager 5.3. RESULT: Six RCTs were included in this meta-analysis. The pooled results suggested that bromelain appears to be effective for decreasing facial swelling in the early and late stages after surgery (early-stage SMD, -0.24; 95% confidence interval [CI], -0.46 to -0.02; P = .03; late-stage SMD, -0.54; 95% CI, -0.84 to -0.24; P = .0004). Bromelain alleviated postoperative pain 7 days after surgery (SMD, -0.54; 95% CI, -0.87 to -0.20; P = .002), but there was no significant difference in pain levels at the early stage. For trismus, analyses showed that bromelain had no apparent effect on early or late trismus. CONCLUSION: Bromelain conferred moderate relief of postoperative discomfort after third molar surgery.


Subject(s)
Analgesics , Bromelains , Pain, Postoperative , Tooth Extraction , Tooth, Impacted , Trismus , Analgesics/therapeutic use , Bromelains/therapeutic use , Edema/drug therapy , Humans , Molar, Third , Pain, Postoperative/drug therapy , Tooth, Impacted/surgery , Trismus/drug therapy
12.
J Craniomaxillofac Surg ; 47(4): 592-601, 2019 Apr.
Article in English | MEDLINE | ID: mdl-30826112

ABSTRACT

The objective of this study was to comprehensively assess the use of tranexamic acid (TXA) during orthognathic surgery. A systematic review and meta-analysis of randomized controlled trials addressing these issues were carried out. Three electronic databases, included PubMed, Web of Science, and Cochrane Library, were searched until April 30, 2018. Eligible studies were restricted to randomized, controlled trials (RCTs). Weighted mean differences (WMD) for blood loss, operation time, haematocrit, quality of surgical field, and odds ratio (OR) for transfusion rates were pooled for the included studies. Eight randomized, controlled trials were included for analysis. Compared with the control group, the TXA group showed a reduction in intraoperative blood loss of 165.03 ml (p < 0.00001; 95% CI, -200.93 to -129.13 ml), a reduction in the drop of haematocrit of 2.32 g/dl (p < 0.00001; 95% CI, -3.38 to -1.26 g/dl), and an improved quality of surgical field (p < 0.00001; MD, -1.01; 95% CI, -1.23 to -0.80). Tranexamic acid has a limited effect on reducing operative time (p < 0.00001; MD, -16.18 min; 95% CI, -19.60 to -12.75 min) and on decreasing the transfusion rates (p = 0.02; OR = 0.33; 95% CI, 0.13 to 0.83).


Subject(s)
Orthognathic Surgery , Antifibrinolytic Agents , Blood Loss, Surgical , Blood Transfusion , Humans , Randomized Controlled Trials as Topic , Tranexamic Acid
13.
J Craniomaxillofac Surg ; 47(1): 6-14, 2019 Jan.
Article in English | MEDLINE | ID: mdl-30471936

ABSTRACT

PURPOSE: To introduce a modified protocol for mandibular reconstruction and evaluate the protocol using a standardized assessment method. METHOD: This retrospective study involved a case series of nine patients who underwent mandibular reconstruction between 2015 and 2017. The modular protocol comprised three novel modifications in terms of computer-assisted surgical simulation (CASS); surgical template (ST), and surgical procedure. The standardized postoperative evaluation consisted of operation time, part comparison analysis (PCA), facial symmetry, and mechanical quantitative sensory testing. RESULTS: The surgery successfully removed the affected mandible and preserved the inferior alveolar neurovascular bundle (IANB). PCA revealed that the mean error and standard deviation were 0.92 and 0.96 mm, respectively, for all mandibular surface sites. Follow-up results showed good facial symmetry, existence of sensation in lower lip, and no significant differences in pulp vitality between both sides (p = 0.181). Also, the results showed a reduction in the overall operating time. CONCLUSION: The modified mandibular reconstruction method used in this study could repair lateral mandibular defects and preserve the sensory function of the chin and lower lip.


Subject(s)
Computer Simulation , Mandible/surgery , Mandibular Reconstruction/methods , Plastic Surgery Procedures/methods , Surgery, Computer-Assisted/methods , Adult , Bone Plates , Bone Screws , Bone Transplantation/methods , Chin/blood supply , Chin/innervation , Chin/physiology , Face/anatomy & histology , Face/blood supply , Face/innervation , Female , Humans , Imaging, Three-Dimensional , Lip/blood supply , Lip/innervation , Lip/physiology , Male , Mandible/blood supply , Mandible/innervation , Mandibular Neoplasms/surgery , Mandibular Nerve , Mandibular Osteotomy/methods , Middle Aged , Orthognathic Surgical Procedures , Osteotomy/methods , Patient Care Planning , Postoperative Care/methods , Retrospective Studies , Sensation , Sensory Thresholds/physiology , Titanium , Young Adult
14.
Medicine (Baltimore) ; 97(10): e9776, 2018 Mar.
Article in English | MEDLINE | ID: mdl-29517694

ABSTRACT

To evaluate the feasibility of the orthodontic traction after local resection of the condylar osteochondroma (OC).From November 2011 to September 2016, consecutive patients with condylar OC who underwent orthodontic extraction after local resection of the mass were reviewed. Clinical data and cone-beam computed tomography (CT) were obtained before treatment (T0), 1 week after surgery (T1), and at least 6-month follow-up after OC resection (T2). Repeated-measures analysis of variance with Bonferroni multiple-comparison test was used to compare the 3-dimensional cephalometric variables at different time points and the paired t test was used to compare changes of temporomandibular joint (TMJ) space between the 2 sides at T1 and T2.The sample consisted of 23 patients (16 females and 7 males). The mean postoperative follow-up interval was 10.9 months. No recurrence was observed during the postoperative follow-up period. Facial symmetry and occlusion were greatly improved. B deviation and the distance of gonion on the OC-affected side to the Frankfort horizontal (FH) were significantly improved from T0 to T1 and T2 (P < .01). The anterior space (AS) and superior space (SS) of the OC-affected side were significantly larger than that of the contralateral side at T1 in parasagittal CT views (P < .05), while no difference was found between the two sides at T2.Local resection is an effective technique with less damage to the condyle. The application of postoperative directional traction could guide the condyle into the fossa, achieve normal TMJ space and stable occlusion, and eventually provide functional and esthetic outcomes.


Subject(s)
Dental Occlusion , Mandibular Condyle/surgery , Mandibular Neoplasms/surgery , Occlusal Adjustment/methods , Osteochondroma/surgery , Adult , Centric Relation , Feasibility Studies , Female , Humans , Male , Mandibular Condyle/pathology , Mandibular Neoplasms/pathology , Middle Aged , Osteochondroma/pathology , Postoperative Period , Temporomandibular Joint/surgery , Young Adult
15.
J Cell Physiol ; 233(9): 6574-6582, 2018 09.
Article in English | MEDLINE | ID: mdl-29057471

ABSTRACT

Delta-like 2 (Dlk2), a glycoprotein highly homologous to Dlk1, belongs to the Notch/Delta/Serrata family. Dlk2 has been shown to be an important regulator of adipogenesis; however, its role in other cellular differentiation processes is still unknown. Therefore, in this study, we aimed to determine the role of Dlk2 in chondrogenic differentiation. We found that Dlk2 overexpression promoted the growth of ATDC5 cells but inhibited insulin-induced ATDC5 chondrogenic differentiation, as supported by the reduction in cartilage matrix formation and gene expression of aggrecan (acan), collagentype II (col2a1) and X (col10a1). In contrast, Dlk2 silencing inhibited the proliferation of ATDC5 cells but enhanced their chondrogenic differentiation. We then evaluated the roles of mitogen-activated protein kinases (MAPKs), which are activated by insulin during the chondrogenesis of ATDC5 cells. Overexpression of Dlk2 protein strongly promoted the activation of p38, but not extracellular signal-regulated kinase (ERK) 1/2 and c-Jun N-terminal kinase (JNK). Moreover, as expected, Dlk2 silencing inhibited the activation of p38, but had no effect on the ERK1/2 and JNK pathways. Finally, we also detected the expression of Dlk2 in mouse epiphyseal cartilage during embryo development. The expression of the Dlk2 protein in the limb bud could be detected at embryonic day 11.5; additionally, it was found to decrease in the superficial zones, but remained unchanged in the deep/hypertrophic zones. In conclusion, our results suggested that Dlk2 acted as an important regulator of chondrogenesis through the p38 pathway. These findings may lead to strategies for the treatment of cartilage-related diseases such as osteoarthritis.


Subject(s)
Cell Differentiation/physiology , Chondrocytes/metabolism , Chondrocytes/physiology , Chondrogenesis/physiology , Intercellular Signaling Peptides and Proteins/metabolism , Aggrecans/metabolism , Animals , Cartilage/metabolism , Cartilage/physiology , Cell Line , Cell Proliferation/physiology , JNK Mitogen-Activated Protein Kinases/metabolism , MAP Kinase Signaling System/physiology , Mice , Mitogen-Activated Protein Kinase 3/metabolism , Mitogen-Activated Protein Kinases/metabolism , Signal Transduction/physiology
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