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

  • Mol Med. 2025 Apr 30;31(1):161. doi: 10.1186/s10020-025-01221-6.
Huanyu Jiang  #  1  2 ,  Yantao Zhang  #  1  2 ,  Piyao Ji  #  1  2 ,  Jianghua Ming  1 ,  Yaming Li  1 ,  Yan Zhou  3  4
Affiliations
  • 1. Department of Orthopedics, Renmin Hospital of Wuhan University, Wuhan, 430060, China.
  • 2. Central Laboratory, Renmin Hospital of Wuhan University, Wuhan, 430060, China.
  • 3. Department of Orthopedics, Renmin Hospital of Wuhan University, Wuhan, 430060, China. [email protected].
  • 4. Central Laboratory, Renmin Hospital of Wuhan University, Wuhan, 430060, China. [email protected].
  • # Contributed equally.
PMID: 40307686 DOI: 10.1186/s10020-025-01221-6
Abstract

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 secretory phenotype (SASP) secretion and ameliorated mitochondrial damage. In the rat OA model, SP-D inhibited aging-related pathological changes by upregulating SIRT3/SOD2 pathway, thereby protecting the cartilage tissue integrity.

Conclusion: These findings indicate that SP-D modulates the inhibition of chondrocyte senescence by upregulating SIRT3/SOD2 pathway. These data indicate that targeting SP-D and the SIRT3/SOD2 pathway might be a promising therapeutic strategy for OA.

Keywords
Chondrocyte; Mitochondria; Osteoarthritis; Senescence; Sirtuin; Superoxide dismutase; Surfactant protein D.
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