S-propargyl-cysteine attenuates temporomandibular joint osteoarthritis by regulating macrophage polarization via Inhibition of JAK/STAT signaling.

BACKGROUND: Temporomandibular joint osteoarthritis (TMJ-OA) is a disease characterized by cartilage degradation and synovial inflammation, with limited effective treatment currently. Synovial macrophage polarization is pivotal in TMJ-OA progression, making it a promising therapeutic aspect. This study investigated the effects of S-propargyl-cysteine (SPRC), an endogenous H2S donor, on macrophage polarization and its therapeutic potential in alleviating TMJ-OA. METHODS: A MIA-induced TMJ-OA rat model and LPS-stimulated RAW264.7 macrophages were employed to evaluate the effects of SPRC in vivo and in vitro. TMJ bone and cartilage were analyzed via micro-CT and histological methods, while macrophage polarization markers expression were assessed via RT-qPCR, western blot, and immunofluorescence. RNA sequencing was performed on macrophages, and the JAK2/STAT3 signaling pathway was validated using the JAK2-specific inhibitor AG490. The direct effects of SPRC on rat primary condylar chondrocytes were examined by evaluating ECM synthesis and degradation. Co-culture experiments further assessed macrophage-chondrocyte interactions. RESULTS: SPRC significantly alleviated cartilage and bone damage in the TMJ-OA rat model, as demonstrated by improved bone volume and cartilage structure. SPRC reduced pro-inflammatory M1 macrophage infiltration and enhanced anti-inflammatory M2 macrophage polarization. SPRC effectively inhibited the JAK2/STAT3, leading to reduction of inflammatory markers, including TNF-α, IL-6, and iNOS. Co-culture experiments revealed that SPRC-treated macrophage-conditioned medium improved chondrocyte metabolic activity and restored ECM integrity. CONCLUSIONS: SPRC-modulated macrophage polarization alleviates TMJ-OA via JAK/STAT downregulation, thereby reducing synovial inflammation and cartilage degradation. These findings position SPRC as a promising therapeutic candidate for TMJ-OA and provide insights into novel strategies targeting macrophage polarization and synovium-cartilage crosstalk.