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<p>Joint contracture resulting from prolonged immobilization is a common complication characterized by pain, stiffness, and limited mobility. Although inflammation and tissue remodeling are known contributors, the underlying cellular mechanisms remain unclear. Here, we investigated the involvement of Caspase-1/GSDMD-mediated pyroptosis in immobilization-induced knee joint contracture and evaluated the therapeutic potential of disulfiram (DSF), an FDA-approved drug repurposed here based on its reported anti-pyroptotic activity. In a rat model of knee immobilization, we assessed joint mobility, histopathological changes, and molecular markers associated with pyroptosis. Immobilization significantly induced contracture, inflammatory infiltration, and activation of the Caspase-1/GSDMD pathway in the joint capsule. Treatment with DSF improved joint range of motion, reduced tissue damage, and reduced caspase-1/GSDMD-related pyroptosis markers and GSDMD cleavage. Notably, DSF decreased IL-1β and IL-18 protein levels without affecting their mRNA expression. Together, these findings support a role for Caspase-1/GSDMD-associated pyroptosis in immobilization-induced joint contracture and suggest that DSF alleviates contracture, at least in part, by modulating this pathway, providing new mechanistic insight and a potential therapeutic approach for preventing post-immobilization joint contracture.</p>

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Disulfiram attenuates immobilization-induced knee joint contracture by suppressing Caspase-1/GSDMD-mediated pyroptosis

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年3月9日

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  • Qian Lu,
  • Xiuli Kan,
  • Quanbing Zhang,
  • Deting Zhu,
  • Zunyu Du,
  • Xueming Li,
  • Han Xiao,
  • Jing Mao,
  • Run Zhang,
  • Yun Zhou

摘要

Joint contracture resulting from prolonged immobilization is a common complication characterized by pain, stiffness, and limited mobility. Although inflammation and tissue remodeling are known contributors, the underlying cellular mechanisms remain unclear. Here, we investigated the involvement of Caspase-1/GSDMD-mediated pyroptosis in immobilization-induced knee joint contracture and evaluated the therapeutic potential of disulfiram (DSF), an FDA-approved drug repurposed here based on its reported anti-pyroptotic activity. In a rat model of knee immobilization, we assessed joint mobility, histopathological changes, and molecular markers associated with pyroptosis. Immobilization significantly induced contracture, inflammatory infiltration, and activation of the Caspase-1/GSDMD pathway in the joint capsule. Treatment with DSF improved joint range of motion, reduced tissue damage, and reduced caspase-1/GSDMD-related pyroptosis markers and GSDMD cleavage. Notably, DSF decreased IL-1β and IL-18 protein levels without affecting their mRNA expression. Together, these findings support a role for Caspase-1/GSDMD-associated pyroptosis in immobilization-induced joint contracture and suggest that DSF alleviates contracture, at least in part, by modulating this pathway, providing new mechanistic insight and a potential therapeutic approach for preventing post-immobilization joint contracture.