Temporomandibular joint (TMJ) osteoarthritis (OA) is a common type of TMJ disorders causing pain and dysfunction in the jaw and surrounding tissues. The causes for TMJ OA are unknown and the underlying mechanism remains to be identified. In this study, we generated genetically-modified mice deficient of two homologous microRNAs, miR-204 and miR-211, both of which were confirmed by in situ hybridization to be expressed in multiple TMJ tissues, including condylar cartilage, articular eminence, and TMJ disc. Importantly, the loss-of-function of miR-204 and miR-211 caused an age-dependent progressive OA-like phenotype, including cartilage degradation and abnormal subchondral bone remodeling. Mechanistically, the TMJ joint deficient of the two microRNAs demonstrated a significant accumulation of RUNX2, a protein directly targeted by miR-204/-211, and upregulations of β-catenin, suggesting a disrupted balance between osteogenesis and chondrogenesis in the TMJ, which may underlie TMJ OA. Moreover, the TMJ with miR-204/-211 loss-of-function displayed an aberrant alteration in both collagen component and cartilage-degrading enzymes and exhibited exacerbated orofacial allodynia, corroborating the degenerative and painful nature of TMJ OA. Together, our results establish a key role of miR-204/-211 in maintaining the osteochondral homeostasis of the TMJ and counteracting OA pathogenesis through repressing the pro-osteogenic factors including RUNX2 and β-catenin.
Keywords: RUNX2; microRNA; orofacial pain; osteoarthritis; temporomandibular joint; β-catenin.
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