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Background <p>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.</p> Methods <p>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.</p> Results <p>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.</p> Conclusions <p>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.</p> Graphical abstract <p></p>

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

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年4月7日

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  • Wenyi Cai,
  • Antong Wu,
  • Zhongxiao Lin,
  • Wei Cao,
  • Janak L. Pathak,
  • Richard T. Jaspers,
  • Rui Li,
  • Xin Li,
  • Kaihan Zheng,
  • Yufu Lin,
  • Na Zhou,
  • Xin Zhang,
  • Yizhun Zhu,
  • Qingbin Zhang

摘要

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.

Graphical abstract