Dataset Information

Hypoxia-inducible factor expression is related to apoptosis and cartilage degradation in temporomandibular joint osteoarthritis.

ABSTRACT:

Background

It remains unclear etiology of cartilaginous tissues in osteoarthritis (OA) lesions. In this study, we hypothesized the accumulation of hypoxia-inducible factor (HIF) and activated apoptosis relate to condylar 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 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 (OD) stress group. The OD group at 4 weeks and 8 weeks had obviously reduced expression of Aggrecan (Acan) and type II collagen (Col II) in cartilage. In contrast, the OD groups had higher levels of ADAM metallopeptidase with thrombospondin type 5 (ADAMTS5) and matrix metallopeptidase 13 (MMP13) in the condylar cartilage than the control group. Moreover, the OD group cartilage had prominent degenerative changes with reduced levels of hypoxia inducible factor 1 alpha (HIF1α) and increased levels of hypoxia inducible factor 2 alpha (HIF2α) and the apoptosis factor Caspase3 in condylar cartilage at 8 weeks.

Conclusion

Thus, abnormal hypoxic conditions inducing Occlusion disorder stress results in cartilage degeneration. opposite expression patterns of HIF1α and HIF2α could be involved in the pathogenesis of condylar cartilage degeneration and chondrocyte apoptosis. HIF2α may provide a potential negative feedback mechanism for HIF1α during cartilage damage.

SUBMITTER: Zhang J

PROVIDER: S-EPMC9202126 | biostudies-literature | 2022 Jun

REPOSITORIES: biostudies-literature

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Publications

Hypoxia-inducible factor expression is related to apoptosis and cartilage degradation in temporomandibular joint osteoarthritis.

Zhang Jun J Hu Yu Y Wang Zihan Z Wu Xuelian X Yang Chun C Yang Hefeng H

BMC musculoskeletal disorders 20220616 1

<h4>Background</h4>It remains unclear etiology of cartilaginous tissues in osteoarthritis (OA) lesions. In this study, we hypothesized the accumulation of hypoxia-inducible factor (HIF) and activated apoptosis relate to condylar cartilage degeneration in vivo.<h4>Methods</h4>Malocclusion stress was applied for 2 weeks, 4 weeks and 8 weeks to induce an OA-like lesion animal model in rats. Histological analysis was performed by H&E staining and Safranin O/fast green staining. The expression levels ...[more]

PMID: 35710352

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Project description:BackgroundsAbnormal cartilage calcification is one of the pathological changes of temporomandibular joint (TMJ) osteoarthritis (OA). Recent studies have reported that exosomes can regulate the formation of abnormal calcified nodules in diseases including atherosclerosis and chronic kidney disease. However, the influences of chondrocyte-derived exosomes on abnormal cartilage calcification in TMJ OA are still unclear.MethodsTMJ OA was induced by unilateral anterior crossbite (UAC) for 4, 8, or 12 weeks in rats to observe abnormal calcification in TMJ condylar cartilage and exosome formation. Concomitantly, GW4869, the inhibitor of exosome formation, was locally injected to the TMJ of rats under stimulation of UAC, while the exosomes extracted from primary condylar chondrocytes stimulated with fluid flow shear stress (FFSS) were locally injected to rats TMJ.ResultsAbnormal calcification was enhanced in the degenerative cartilage of TMJ OA in UAC rats, and a large number of exosome-like structures with diameters of 50-150 nm were found in the calcified cartilage together with decreased expression of matrix Gla protein (MGP) and increased expression of CD63, tissue-nonspecific alkaline phosphatase (TNAP) and nucleotide pyrophosphatase/phosphodiesterase-1 (NPP1). After FFSS stimulation, the number of exosomes secreted by chondrocytes and the numbers of calcified nodules were increased in cultured cells, and the protein levels of MGP, TNAP, and NPP1 in exosomes were changed. Inhibition of exosome formation, TNAP, and NPP1 or supplementation with exogenous MGP effectively alleviated FFSS-induced chondrocyte calcification. Local injection of GW4869, the exosome inhibitor, alleviated TMJ OA-related cartilage degeneration and calcification in UAC rats. Local injection of exosomes obtained from chondrocytes stimulated by FFSS to the TMJs of normal rats induced cartilage degeneration and calcification similar to that in TMJ OA.ConclusionsAbnormal biomechanical loading leads to enhanced formation of chondrocyte-derived exosomes, in which promoters of calcification increased and inhibitors decreased, resulting in accelerating abnormal cartilage calcification in TMJ OA. The inhibition of degenerative chondrocyte-derived exosomes is expected to be a new way to prevent and treat TMJ OA.

Dataset Information

Hypoxia-inducible factor expression is related to apoptosis and cartilage degradation in temporomandibular joint osteoarthritis.

Background

Methods

Results

Conclusion

Publications

Hypoxia-inducible factor expression is related to apoptosis and cartilage degradation in temporomandibular joint osteoarthritis.

Similar Datasets

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