Scholarlink

Background <p>Osteoarthritis (OA) is a degenerative disease with incompletely understood mechanisms. The proteasome subunit PSMB9 has been implicated in immune regulation, but its specific role in OA pathogenesis remains unclear. This study aimed to investigate whether PSMB9 mediates IL-1β–induced chondrocyte injury by activating the NF-κB pathway through promoting IκBα degradation, and to explore the regulatory relationship between IL-6 and PSMB9 in OA progression.</p> Methods <p>Differentially expressed genes were identified by integrating human and mouse OA datasets. A mouse destabilization of the medial meniscus (DMM) model was established. The function of PSMB9 in OA chondrocytes and its effect on the NF-κB pathway were analyzed using hematoxylin–eosin (H&amp;E) staining, immunohistochemistry, Western blot, CCK-8, Edu, flow cytometry, and immunofluorescence to observe p65 nuclear translocation.</p> Results <p>(1) PSMB9 was significantly upregulated in multiple OA datasets and models; (2) PSMB9 expression increased in the cartilage of OA patients and mice; (3) PSMB9 overexpression exacerbated IL-1β-induced chondrocyte apoptosis, inhibited proliferation, upregulated the expression of the inflammatory factor IL-6 and the matrix-degrading enzyme MMP13, promoted extracellular matrix (ECM) degradation, and decreased COL2A1 expression; (4) PSMB9 activated the NF-κB pathway by promoting IκBα degradation, and inhibition of this pathway alleviated cell injury; (5) silencing IL-6 reduced PSMB9 expression.</p> Conclusion <p>PSMB9 may participate in the activation of the NF-κB pathway and potentially contribute to chondrocyte injury in OA, making it a promising target for future research.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

PSMB9 exacerbates chondrocyte injury in osteoarthritis via activation of the NF-κB pathway

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年3月14日

查看全文
  • Lianhui Zhao,
  • Jianliang Ou,
  • Sijie Bian,
  • Zhangwei Wu,
  • Xu Wang,
  • Shuo Shi,
  • Xin Liu,
  • Kaida Bo,
  • Daizhi Shi,
  • Jun Chang

摘要

Background

Osteoarthritis (OA) is a degenerative disease with incompletely understood mechanisms. The proteasome subunit PSMB9 has been implicated in immune regulation, but its specific role in OA pathogenesis remains unclear. This study aimed to investigate whether PSMB9 mediates IL-1β–induced chondrocyte injury by activating the NF-κB pathway through promoting IκBα degradation, and to explore the regulatory relationship between IL-6 and PSMB9 in OA progression.

Methods

Differentially expressed genes were identified by integrating human and mouse OA datasets. A mouse destabilization of the medial meniscus (DMM) model was established. The function of PSMB9 in OA chondrocytes and its effect on the NF-κB pathway were analyzed using hematoxylin–eosin (H&E) staining, immunohistochemistry, Western blot, CCK-8, Edu, flow cytometry, and immunofluorescence to observe p65 nuclear translocation.

Results

(1) PSMB9 was significantly upregulated in multiple OA datasets and models; (2) PSMB9 expression increased in the cartilage of OA patients and mice; (3) PSMB9 overexpression exacerbated IL-1β-induced chondrocyte apoptosis, inhibited proliferation, upregulated the expression of the inflammatory factor IL-6 and the matrix-degrading enzyme MMP13, promoted extracellular matrix (ECM) degradation, and decreased COL2A1 expression; (4) PSMB9 activated the NF-κB pathway by promoting IκBα degradation, and inhibition of this pathway alleviated cell injury; (5) silencing IL-6 reduced PSMB9 expression.

Conclusion

PSMB9 may participate in the activation of the NF-κB pathway and potentially contribute to chondrocyte injury in OA, making it a promising target for future research.