Delay of Condylar Cartilage Degeneration by Conditional Removal of Discoidin Domain Receptor 2 in Temporomandibular Joint of a Mouse Model of 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.

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Pyroptosis Related Molecules are Significant for Cartilage Degeneration

10.21203/rs.3.rs-104795/v1 ◽

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.

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Age-dependent increase of discoidin domain receptor 2 and matrix metalloproteinase 13 expression in temporomandibular joint cartilage of type IX and type XI collagen-deficient mice

Archives of Oral Biology ◽

10.1016/j.archoralbio.2006.10.014 ◽

2007 ◽

Vol 52 (6) ◽

pp. 579-584 ◽

Cited By ~ 21

Author(s):

N.P. Lam ◽

Y. Li ◽

A.B. Waldman ◽

J. Brussiau ◽

P.L. Lee ◽

...

Keyword(s):

Matrix Metalloproteinase ◽

Temporomandibular Joint ◽

Joint Cartilage ◽

Discoidin Domain Receptor ◽

Matrix Metalloproteinase 13 ◽

Age Dependent ◽

Type Xi Collagen ◽

Discoidin Domain Receptor 2 ◽

Deficient Mice

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Effect of high fat diet and excessive compressive mechanical force on pathologic changes of temporomandibular joint

Scientific Reports ◽

10.1038/s41598-020-74326-z ◽

2020 ◽

Vol 10 (1) ◽

Author(s):

Jing Du ◽

Qian Jiang ◽

Li Mei ◽

Ren Yang ◽

Juan Wen ◽

...

Keyword(s):

Mouse Model ◽

Mrna Expression ◽

Temporomandibular Joint ◽

High Fat Diet ◽

Mechanical Force ◽

Pathological Changes ◽

High Fat ◽

Condylar Cartilage ◽

Diet Induced Obesity

Abstract The aim of this study was to investigate the effect of high fat diet and excessive compressive mechanical force on temporomandibular joint. In vivo, a mouse model of temporomandibular joint compressive loading device was used. A high fat diet mouse model and a combined mouse model intraperitoneally treated with or without simvastatin were used in the study. The pathological changes of mandibular condylar cartilage were assessed by Safranin-O staining. The IL-1β, MMP-3, leptin expression changes in the cartilage were detected by immunohistochemistry. In vitro, the mandibular condylar chondrocytes were treated with or without L-1β and simvastatin. The mRNA expression level of matrix MMPs and leptin were assessed. Both excessive compressive mechanical force and high fat diet induced obesity caused TMJ osteoarthritis-like changes and increased expression of IL-1β, MMP-3, and leptin. These pathological changes were much more serious when the two interventions were exerted together, while simvastatin could obviously alleviate these changes. The mRNA expression of MMP-3, MMP-13, and leptin increased in the IL-1β treated chondrocytes treated with IL-1β, and decreased with simvastatin treatment. The development of temporomandibular joint pathological changes could be caused by the excessive compressive mechanical force and high fat diet induced obesity.

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