Abstract

Pannexin 3 (Panx3) is involved in regulation of the proliferation and differentiation in chondrocytes and pathological process in osteoarthritis, but its role and potential mechanism in temporomandibular joint osteoarthritis (TMJOA) are still unclear, which are thus explored in our research. We established TMJOA animal model and cell model. In vivo, after silencing Panx3, the pathological changes of condylar cartilage tissue were analyzed by tissue staining, while expressions of Panx3, P2X7 receptor (P2X7R), NLRP3, and cartilage matrix-related genes were measured by immunohistochemistry (for animal model) or immunofluorescence (for cell model), quantitative reverse-transcription polymerase chain reaction (qRT-PCR) or western blot. In addition, the activation of inflammation-related pathways was detected by qRT-PCR or western blot, and intracellular adenosine triphosphate (ATP) level was tested by ATP kit. The role of Panx3 in TMJOA was proved by loss- and gain-of-function assays. P2X7R antagonist was employed to verify the relationship between Panx3 and P2X7R. Panx3 silencing alleviated the damage of condyle cartilage tissue in TMJOA rats, and reduced expressions of Panx3, P2X7R, cartilage matrix degradation related-enzymes, and NLRP3 in condyle cartilage tissue. In TMJOA cell model, the expressions of Panx3, P2X7R, cartilage matrix degradation related-enzymes were increased, and inflammation-related pathways were activated, meanwhile interleukin-1β treatment promoted the release of intracellular ATP to the extracellular space. The above-mentioned response was enhanced by Panx3 overexpression and reversed by Panx3 silencing. P2X7R antagonist reversed the regulation of Panx3 overexpression. In conclusion, Panx3 may activate P2X7R by releasing ATP to mediate inflammation and cartilage matrix degradation in TMJOA.