Surfactant protein D alleviates chondrocytes senescence by upregulating SIRT3/SOD2 pathway in osteoarthritis

作者：Huanyu Jiang, Yantao Zhang, Piyao Ji, Jianghua Ming, Yaming Li, Yan Zhou · 发表于：Molecular Medicine · 年份：2025 · DOI：10.1186/s10020-025-01221-6 · 被引用次数：5 · 研究领域：Osteoarthritis Treatment and Mechanisms、Neonatal Respiratory Health Research、Fatty Acid Research and Health

BACKGROUND: Osteoarthritis (OA) is an age-related degenerative disease that affects bones and joints. The hallmark pathogenesis of OA is associated with chondrocyte senescence. Surfactant protein D (SP-D) is a member of the innate immune proteins family, which can inhibit the immune inflammatory response of chondrocytes. However, the effect of SP-D on chondrocyte senescence phenotype is poorly studied. The present study investigated the phenotypic regulation of OA chondrocyte senescence mediated by SP-D and explored the underlying molecular mechanism. METHODS: In this study, an in vitro senescence chondrocyte model was generated by subjecting chondrocytes to IL-1β treatment. Furthermore, the expression of aging-related biomarkers and mitochondrial functions in SP-D overexpressing chondrocytes was observed. Co-immunoprecipitation was conducted to verify the association between SP-D and the identifed proteins within chondrocytes. Moreover, a rat OA model was established by destabilization of the medial meniscus surgery, and the effect of SP-D on reversing the aging phenotype of OA cartilage was investigated. RESULTS: The results indicated that SP-D significantly decreased senescence and enhanced mitochondrial functions in senescent chondrocytes. The RNA-sequencing analysis revealed that the SIRT3/SOD2 pathway predominantly modulated the effect of SP-D on alleviating senescence. In addition, SP-D overexpression mitigated chondrocyte senescence, suppressed senescence-associated s...