scholarly journals Hypoxia-inducible Factor Expression Is Related to Apoptosis and Cartilage Degradation in Temporomandibular Joint Osteoarthritis

2022 ◽  
Author(s):  
Jun Zhang ◽  
Yu Hu ◽  
Zihan Wang ◽  
Xuelian Wu ◽  
Chun Yang ◽  
...  
Keyword(s):  
Temporomandibular Joint ◽  
Expression Patterns ◽  
Cartilage Damage ◽  
Hypoxia Inducible Factor ◽  
Cartilage Degeneration ◽  
Chondrocyte Apoptosis ◽  
Control Group ◽  
Condylar Cartilage ◽  
Hypoxic Conditions ◽  
Temporomandibular Joint Osteoarthritis

Abstract Background: It remains unclear whether hypoxic conditions affect apoptosis and contribute to degradation of cartilaginous tissues in osteoarthritis (OA) lesions. In this study, we hypothesized that hypoxic conditions induced the accumulation of hypoxia-inducible factor (HIF) and activated apoptosis to contribute to OA cartilage degeneration in vivo.Methods: Malocclusion stress was applied for 2 weeks, 4 weeks and 8 weeks to induce an OA-like lesion animal model (OD) in rats. Histological analysis was performed by H&E staining and safranin O/fast green staining. The expression levels of protein in condylar cartilage were examined by immunostaining to evaluate cartilage degeneration.Results: We found apparent histological phenotypes associated with degeneration in the occlusion disorder stress (OD) group. The OD group at 4 weeks and 8 weeks had obviously reduced expression of Acan and Col II in cartilage. In contrast, the OD groups had higher levels of Col X, ADAMTS5 and MMP13 in the condylar cartilage than the control group. Moreover, the OD group cartilage had prominent degenerative changes with reduced levels of HIF1α and increased levels of HIF2α and the apoptosis factor Caspase3 in condylar cartilage at 8 weeks.Occlusion disorder stress results in cartilage degeneration. HIF1α and HIF2α are involved in temporomandibular joint (TMJ) cartilage homeostasis by regulating chondrocyte apoptosis, which contributes to TMJ cartilage degeneration. Conclusion: Thus, abnormal hypoxic conditions inducing opposite expression patterns of HIF1α and HIF2α could be involved in the pathogenesis of condylar cartilage degeneration. HIF2α may provide a potential negative feedback mechanism for HIF1α during cartilage damage.

scholarly journals C-Reactive Protein Knock Out Attenuate Temporomandibular Joint Inflammation in Rats

2020 ◽  
Author(s):  
Yao He ◽  
Mengjiao Zhou ◽  
Zixiang Jian ◽  
Lingli Fang ◽  
Lan Huang ◽  
...  
Keyword(s):  
Temporomandibular Joint ◽  
Morphological Changes ◽  
Osteoclast Differentiation ◽  
Joint Inflammation ◽  
Cartilage Degeneration ◽  
Control Group ◽  
C Reactive Protein ◽  
Knock Out ◽  
Reactive Protein ◽  
Temporomandibular Joint Osteoarthritis

Abstract Background: C-reactive protein (CRP), as the biomarker for inflammation, high expresses in osteoarthritis (OA) related diseases with exact role been clouded. In this study, we evaluated the biological effect of CRP in temporomandibular joint osteoarthritis (TMJ-OA).Methods: Freund’s complete adjuvant (CFA) was used for TMJ inflammation induction in CRP knock out (CRP -/-) and control rats. And TMJ degenerative changes, such as the synovitis performance, TMJ disc morphological changes and cartilage degeneration were compared to elucidate the role of CRP played in TMJ-OA. Results: Compared to control group, CFA induced TMJ inflammation caused systemic and local CRP expression increased. Based on this, CRP -/- rat performed less severe inflammation symptoms. Lower degree of pro-inflammatory cytokines (interleukins IL-1β and IL-6) expression and up-expression of anti-inflammatory cytokine IL-10 were detected in CRP -/- rat, which with less macrophage and activation and osteoclast differentiation.Conclusion: These results indicated that control high elevated CRP level during inflammation should be benefit for TMJ-OA prevention and treatment.

scholarly journals Pyroptosis Related Molecules are Significant for Cartilage Degeneration

2020 ◽  
Author(s):  
Mengying Jia ◽  
Yaoguang Lv ◽  
Yingjie Xu ◽  
Zhoncheng Gong
Keyword(s):  
Temporomandibular Joint ◽  
Cartilage Degeneration ◽  
Enzyme Linked Immunosorbent Assay ◽  
Therapeutic Effects ◽  
Clinical Effects ◽  
Condylar Cartilage ◽  
Pyrin Domain ◽  
Temporomandibular Joint Osteoarthritis ◽  
Significant Difference ◽  
Temporomandibular Joint Internal Derangement

Abstract Background: Pyroptosis is the highlight topic in inflammation. However, there is rarely research on relationship between pyroptosis and temporomandibular joint osteoarthritis (TMJOA), The aim of this study is to explore whether pyroptosis related molecules are significant for condylar cartilage degeneration and to verify the clinical effects of sodium hyaluronic acid (HA) treatment on TMJOA.Methods: Patients diagnosed as temporomandibular joint internal derangement (TMJID) without condylar defect and TMJOA with condylar defect were divided into two groups. Thirty patients in each group, and they were tested for pyroptosis related molecules via synovial fluid included interleukin-1beta (IL-1β), IL-18, nucleotide-binding oligomerization domain-like receptor pyrin domain containing 3 (NLRP3), cysteinyl aspartate specific proteinase 1 (CASP1) with Enzyme-linked immunosorbent assay（Elisa）. Eighteen cases in TMJOA group were tested again after twice HA treatment to evaluate HA’s therapeutic effects. Results: IL-1β, IL-18, NLRP3 and CASP1 were all positive in two groups, TMJOA patients with condylar defect had higher expressions of above molecules compared with TMJID patients (P＜0.05). IL-1β, IL-18, NLRP3 were decreased with twice HA therapy (P＜0.05), there was no significant difference in CASP1 with twice HA injections (P=0.549). Conclusions: Cell pyroptosis may be involved in condylar degeneration. HA could reduce part of pyroptosis molecules to relieve inflammation.

scholarly journals The Attenuating Effect of Low-Intensity Pulsed Ultrasound on Hypoxia-Induced Rat Chondrocyte Damage in TMJ Osteoarthritis Based on TMT Labeling Quantitative Proteomic Analysis

2021 ◽  
Vol 12 ◽  
Author(s):  
Sa Du ◽  
Chao Liang ◽  
Yujie Sun ◽  
Bowen Ma ◽  
Wenmo Gao ◽  
...  
Keyword(s):  
Treatment Group ◽  
Control Group ◽  
Pulsed Ultrasound ◽  
Condylar Cartilage ◽  
Low Intensity Pulsed Ultrasound ◽  
Network Analyses ◽  
Low Intensity ◽  
Hypoxic Conditions ◽  
Oxygen Treatment ◽  
Temporomandibular Joint Osteoarthritis

Temporomandibular joint osteoarthritis (TMJOA) is a degenerative disease with a complex and multifactorial etiology. An increased intrajoint pressure or weakened penetration can exacerbate the hypoxic state of the condylar cartilage microenvironment. Our group previously simulated the hypoxic environment of TMJOA in vitro. Low-intensity pulsed ultrasound (LIPUS) stimulation attenuates chondrocyte matrix degradation via a hypoxia-inducible factor (HIF) pathway-associated mechanism, but the mode of action of LIPUS is currently poorly understood. Moreover, most recent studies investigated the pathological mechanisms of osteoarthritis, but no biomarkers have been established for assessing the therapeutic effect of LIPUS on TMJOA with high specificity, which results in a lack of guidance regarding clinical application. Here, tandem mass tag (TMT)-based quantitative proteomic technology was used to comprehensively screen the molecular targets and pathways affected by the action of LIPUS on chondrocytes under hypoxic conditions. A bioinformatic analysis identified 902 and 131 differentially expressed proteins (DEPs) in the <1% oxygen treatment group compared with the control group and in the <1% oxygen + LIPUS stimulation group compared with the <1% oxygen treatment group, respectively. The DEPs were analyzed by gene ontology (GO), KEGG pathway and protein-protein interaction (PPI) network analyses. By acting on extracellular matrix (ECM)-associated proteins, LIPUS increases energy production and activates the FAK signaling pathway to regulate cell biological behaviors. DEPs of interest were selected to verify the reliability of the proteomic results. In addition, this experiment demonstrated that LIPUS could upregulate chondrogenic factors (such as Sox9, Collagen Ⅱ and Aggrecan) and increase the mucin sulfate content. Moreover, LIPUS reduced the hydrolytic degradation of the ECM by decreasing the MMP3/TIMP1 ratio and vascularization by downregulating VEGF. Interestingly, LIPUS improved the migration ability of chondrocytes. In summary, LIPUS can regulate complex biological processes in chondrocytes under hypoxic conditions and alter the expression of many functional proteins, which results in reductions in hypoxia-induced chondrocyte damage. ECM proteins such as thrombospondin4, thrombospondin1, IL1RL1, and tissue inhibitors of metalloproteinase 1 play a central role and can be used as specific biomarkers determining the efficacy of LIPUS and viable clinical therapeutic targets of TMJOA.

Effect of Mechanical Stress on Rheumatoid Arthritis of the Temporomandibular Joint: a Morphological and Histological Evaluation

2021 ◽  
Author(s):  
Kohei Nagai ◽  
Takenobu Ishii ◽  
Yasushi Nishii
Keyword(s):  
Rheumatoid Arthritis ◽  
T Cell ◽  
Mechanical Stress ◽  
Temporomandibular Joint ◽  
Mandibular Condyle ◽  
Γδ T Cells ◽  
Histological Evaluation ◽  
Control Group ◽  
Condylar Cartilage ◽  
Layer Width

Abstract Background Rheumatoid arthritis of the temporomandibular joint (TMJ-RA) has been reported to have a larger incidence range than systemic rheumatoid arthritis (RA). The presence or absence of mechanical stress (MS) is considered a factor in this. In this study, we hypothesized that TMJ-RA develops or worsens when excessive MS is applied to the temporomandibular joint of RA mouse models. We aimed to clarify the relationship between TMJ-RA and MS through morphological and histological evaluation. Methods Collagen antibody-induced arthritis (CAIA) was induced in male DBA/1JNCrlj 9–12 weeks old mice by administering Type II collagen antibody and lipopolysaccharide to produce RA model mice. MS was applied to the mandibular condyle. The group was separated into non-RA (control group (N = 5) and MS group (N = 5)), and RA group (CAIA group (N = 5)and CAIA MS group (N = 5)). To confirm the morphological changes in the mandibular condyle, micro-CT imaging was performed. Histological evaluation of the TMJ was performed by hematoxylin and eosin staining for condylar cartilage cell layer thickness, Safranin O staining for proteoglycans, and tartrate-resistant acidic phosphatase staining for osteoclast count. Immunohistochemical evaluation was performed to assess the localization of cartilage destruction enzymes using ADAMTS-5 (a disintegrin and metalloproteinase with thrombospondin motifs) antibody. Additionally, CD3 (cluster of differentiation), CD45, and γδ TCR (T cell receptor) antibodies were used to localize and identify the type of lymphocytes. Results In the CAIA MS model, a three-dimensional analysis of the temporomandibular joint by microcomputer tomography showed a crude change in the surface of the mandibular condyle. Histological examination revealed a decrease in the chondrocyte layer width and an increase in the number of osteoclasts in the mandibular condyle. T cell accumulation was observed, and γδ T cell involvement was confirmed. Conclusions In the CAIA model, the TMJ was less sensitive to the initiation of RA. However, the results suggested that it was exacerbated by MS, and that γδ T cells may be involved in TMJ-RA.

Effect of functional lateral shift of the mandible on hyaluronic acid metabolism related to lubrication of temporomandibular joint in growing rats

2020 ◽  
Vol 42 (6) ◽  
pp. 658-663
Author(s):  
Xiyuan Guo ◽  
Ippei Watari ◽  
Yuhei Ikeda ◽  
Wu Yang ◽  
Takashi Ono
Keyword(s):  
Hyaluronic Acid ◽  
Articular Cartilage ◽  
Temporomandibular Joint ◽  
Experimental Period ◽  
Lateral Shift ◽  
Control Group ◽  
Condylar Cartilage ◽  
Growing Rats ◽  
Shift Group ◽  
Recovery Group

Summary Background Hyaluronic acid (HA) is a major molecular component of the articular cartilage of the temporomandibular joint (TMJ) influencing joint lubrication. Functional lateral shift of the mandible (FLSM) can lead to malocclusion. This study investigated the effects of FLSM on HA metabolism and lubrication of the TMJ in growing rats. Methods Thirty 5-week-old male Wistar rats were divided into shift, recovery, and control groups. Rats in the shift and recovery groups were fitted with guiding plates to produce a 2-mm FLSM which were removed from the rats in the recovery group 14 days later. Animals were sacrificed at 14 and 28 days after the appliances were attached. Immunohistochemistry of HA-binding protein (HABP), hyaluronan synthase (HAS), and hyaluronoglucosaminidases (HYALs) was examined. Results The thickness of HABP-positively stained areas in the lateral regions in the bilateral condyle was reduced during the experimental period in the shift group compared with that in the control group. The proportion of HAS2-stained areas was bilaterally decreased in different regions of condylar cartilage during the experimental period in the shift group. The reduction of the HYAL2-stained area proportion in the condylar cartilage was more significant than that of HYAL1 at 14 days after appliance attachment in the shift group. HAS2 staining was not recovered in the recovery group. Limitations This research was based on animal experiments with a limited experimental period. Conclusion FLSM altered lubrication related HA metabolism in the articular cartilage of the TMJ in growing rats.

scholarly journals Emerging Potential of Exosomes in Regenerative Medicine for Temporomandibular Joint Osteoarthritis

2020 ◽  
Vol 21 (4) ◽  
pp. 1541 ◽  
Author(s):  
Yeon-Hee Lee ◽  
Hee-Kyung Park ◽  
Q-Schick Auh ◽  
Haram Nah ◽  
Jae Seo Lee ◽  
...  
Keyword(s):  
Regenerative Medicine ◽  
Temporomandibular Joint ◽  
Biological Fluids ◽  
Therapeutic Effects ◽  
Self Healing ◽  
Condylar Cartilage ◽  
Differentiation Potential ◽  
Immune Effector ◽  
Tissue Repair And Regeneration ◽  
Temporomandibular Joint Osteoarthritis

Exosomes are nanosized vesicles (30–140 nm) of endocytic origin that play important roles in regenerative medicine. They are derived from cell membranes during endocytic internalization and stabilize in biological fluids such as blood and synovia. Temporomandibular joint osteoarthritis (TMJ OA) is a degenerative disease, which, in addition to chronic pain, is characterized by progressive cartilage breakdown, condylar bone remodeling, and synovitis. However, traditional clinical treatments have limited symptom- and structure-modifying effects to restore damaged cartilage and other TMJ tissues. This is due to the limited self-healing capacity of condylar cartilage. Recently, stem-cell-derived exosomes have been studied as an alternative therapeutic approach to tissue repair and regeneration. It is known that trophic regulation of mesenchymal stem cells (MSCs) has anti-inflammatory and immunomodulatory effects under pathological conditions, and research on MSC-derived exosomes is rapidly accumulating. MSC-derived exosomes mimic the major therapeutic effects of MSCs. They affect the activity of immune effector cells and possess multilineage differentiation potential, including chondrogenic and osteogenic differentiation. Furthermore, exosomes are capable of regenerating cartilage or osseous compartments and restoring injured tissues and can treat dysfunction and pain caused by TMJ OA. In this review, we looked at the uniqueness of TMJ, the pathogenesis of TMJ OA, and the potential role of MSC-derived exosomes for TMJ cartilage and bone regeneration.

scholarly journals Mesenchymal Stem Cells for Cartilage Regeneration of TMJ Osteoarthritis

2017 ◽  
Vol 2017 ◽  
pp. 1-11 ◽  
Author(s):  
Dixin Cui ◽  
Hongyu Li ◽  
Xin Xu ◽  
Ling Ye ◽  
Xuedong Zhou ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Cartilage Regeneration ◽  
Cartilage Degeneration ◽  
Self Healing ◽  
Condylar Cartilage ◽  
Differentiation Potential ◽  
Tissue Repair And Regeneration ◽  
Cell Based Therapy ◽  
Temporomandibular Joint Osteoarthritis

Temporomandibular joint osteoarthritis (TMJ OA) is a degenerative disease, characterized by progressive cartilage degradation, subchondral bone remodeling, synovitis, and chronic pain. Due to the limited self-healing capacity in condylar cartilage, traditional clinical treatments have limited symptom-modifying and structure-modifying effects to restore impaired cartilage as well as other TMJ tissues. In recent years, stem cell-based therapy has raised much attention as an alternative approach towards tissue repair and regeneration. Mesenchymal stem cells (MSCs), derived from the bone marrow, synovium, and even umbilical cord, play a role as seed cells for the cartilage regeneration of TMJ OA. MSCs possess multilineage differentiation potential, including chondrogenic differentiation as well as osteogenic differentiation. In addition, the trophic modulations of MSCs exert anti-inflammatory and immunomodulatory effects under aberrant conditions. Furthermore, MSCs combined with appropriate scaffolds can form cartilaginous or even osseous compartments to repair damaged tissue and impaired function of TMJ. In this review, we will briefly discuss the pathogenesis of cartilage degeneration in TMJ OA and emphasize the potential sources of MSCs and novel approaches for the cartilage regeneration of TMJ OA, particularly focusing on the MSC-based therapy and tissue engineering.

scholarly journals The Antioxidant Resveratrol Protects against Chondrocyte Apoptosis by Regulating the COX-2/NF-κB Pathway in Created Temporomandibular Osteoarthritis

2021 ◽  
Vol 2021 ◽  
pp. 1-7
Author(s):  
Wen Li ◽  
Shiyu Hu ◽  
Xuepeng Chen ◽  
Jiejun Shi
Keyword(s):  
Morphological Changes ◽  
Critical Role ◽  
Chondrocyte Apoptosis ◽  
Optimum Dose ◽  
Protective Effects ◽  
Condylar Cartilage ◽  
Temporomandibular Joint Osteoarthritis ◽  
Cox 2 ◽  
Antioxidant Effects

Temporomandibular joint osteoarthritis (TMJOA) is characterized by chronic inflammatory degradation of mandibular condylar cartilage (MCC). Studies have found a positive correlation between inflammation and cyclooxygenase- (COX-) 2 in OA pathology. NF-κB is a crucial transcription factor of inflammatory and immune responses in the cause of TMJOA pathology. Resveratrol (RES) plays a critical role in antioxidation and anti-inflammation. But, studies on the effects of RES on TMJOA are very limited. So, the purpose of this study is to investigate the antioxidant and protective effects of RES against MCC degradation through downregulating COX-2/NF-κB expression. In vitro studies, the MCC cells were divided into three groups: the NC group, OA group, and RES group. The optimum dose of RES (10 μM) was determined. The TMJOA model of mice was created by injection of collagenase. And mice were injected with RES (100 μg/10 μl) 3 times one week for 4 weeks in the RES group. The expressions of COX-2, P65, MMP1, MMP13, COL2, and ACAN were measured by RT-PCR. Morphological changes of MCC were studied with HE staining. The results showed that inflammation could induce MCC degradation in vitro and vivo, while RES could reverse the degradation. Meanwhile, RES could downregulate COX-2/NF-κB/MMP expression and increase cartilage markers in vitro and vivo studies. The results indicated that RES treatment had antioxidant effects against chondrocyte apoptosis by downregulating the COX-2/NF-κB pathway in created TMJOA.

scholarly journals IL-1β Damages Fibrocartilage and Upregulates MMP-13 Expression in Fibrochondrocytes in the Condyle of the Temporomandibular Joint

2019 ◽  
Vol 20 (9) ◽  
pp. 2260 ◽  
Author(s):  
Hessam Tabeian ◽  
Beatriz F. Betti ◽  
Cinthya dos Santos Cirqueira ◽  
Teun J. de Vries ◽  
Frank Lobbezoo ◽  
...  
Keyword(s):  
Gene Expression ◽  
Temporomandibular Joint ◽  
Mechanical Loading ◽  
Cartilage Damage ◽  
Cartilage Degradation ◽  
Mechanical Stimuli ◽  
Condylar Cartilage ◽  
Catabolic Enzymes ◽  
Mechanical Tensile ◽  
And Function

The temporomandibular joint (TMJ), which differs anatomically and biochemically from hyaline cartilage-covered joints, is an under-recognized joint in arthritic disease, even though TMJ damage can have deleterious effects on physical appearance, pain and function. Here, we analyzed the effect of IL-1β, a cytokine highly expressed in arthritic joints, on TMJ fibrocartilage-derived cells, and we investigated the modulatory effect of mechanical loading on IL-1β-induced expression of catabolic enzymes. TMJ cartilage degradation was analyzed in 8–11-week-old mice deficient for IL-1 receptor antagonist (IL-1RA−/−) and wild-type controls. Cells were isolated from the juvenile porcine condyle, fossa, and disc, grown in agarose gels, and subjected to IL-1β (0.1–10 ng/mL) for 6 or 24 h. Expression of catabolic enzymes (ADAMTS and MMPs) was quantified by RT-qPCR and immunohistochemistry. Porcine condylar cells were stimulated with IL-1β for 12 h with IL-1β, followed by 8 h of 6% dynamic mechanical (tensile) strain, and gene expression of MMPs was quantified. Early signs of condylar cartilage damage were apparent in IL-1RA−/− mice. In porcine cells, IL-1β strongly increased expression of the aggrecanases ADAMTS4 and ADAMTS5 by fibrochondrocytes from the fossa (13-fold and 7-fold) and enhanced the number of MMP-13 protein-expressing condylar cells (8-fold). Mechanical loading significantly lowered (3-fold) IL-1β-induced MMP-13 gene expression by condylar fibrochondrocytes. IL-1β induces TMJ condylar cartilage damage, possibly by enhancing MMP-13 production. Mechanical loading reduces IL-1β-induced MMP-13 gene expression, suggesting that mechanical stimuli may prevent cartilage damage of the TMJ in arthritic patients.

scholarly journals Protective Effect of Genistein on Condylar Cartilage through Downregulating NF-κB Expression in Experimentally Created Osteoarthritis Rats

2019 ◽  
Vol 2019 ◽  
pp. 1-6 ◽  
Author(s):  
Jian Yuan ◽  
Wanghui Ding ◽  
Na Wu ◽  
Shijie Jiang ◽  
Wen Li
Keyword(s):  
Protective Effect ◽  
Temporomandibular Joint ◽  
Inflammatory Cytokines ◽  
Morphological Changes ◽  
High Dose ◽  
Therapeutic Effects ◽  
Condylar Cartilage ◽  
Positive Effects ◽  
Temporomandibular Joint Osteoarthritis ◽  
Genistein Treatment

Temporomandibular joint osteoarthrosis (TMJOA) is characterised by chronic inflammatory changes, with subsequent gradual loss of joint cartilage. NF-κB is a crucial transcription factor in the course of inflammatory and immune responses, which are involved in OA pathology activated by proinflammatory cytokines. Genistein is known to have anti-inflammation and modulation of metabolic pathways through repression of the NF-κB signaling pathway in inflammatory disease. But so far, studies on the effects of genistein on TMJOA are very limited. So, the purpose of this study is to investigate the protective effect of genistein against experimentally induced condylar cartilage degradation through downregulating NF-κB expression in created osteoarthritis rats in vivo. Male SD rats were created as temporomandibular joint osteoarthritis models and administered through oral gavage with low and high dosage genistein (30 mg/kg and 180 mg/kg, respectively) daily for 4 weeks. The morphological changes of the condylar cartilage were studied with HE and Masson staining. The expressions of p65 and inflammatory cytokines (IL-1β and TNFα) were detected using immunohistochemistry and real-time PCR. The results showed that experimentally created osteoarthritis reduced the condylar cartilage thickness of rats and increased the gene expression of cytokines (IL-1β and TNFα) and positive cells of p65. Genistein treatment had positive effects on the condylar cartilage renovation, while high dose genistein treatment had more significant effects on the reversing of OA changes and reduction of the expression of p65 and inflammatory cytokines (IL-1β and TNFα). The results indicated that high dose genistein treatment had obvious therapeutic effects on condyle cartilage damages of OA rats. The mechanism may be that genistein suppresses the NF-κB expression activated by inflammatory cytokines.

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