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Objective <p>Nuclear transcription factor-κB (NF-κB) activation is a pivotal event in the pathogenesis of osteoarthritis (OA). OA patients frequently exhibit vitamin D (VD) deficiency, which is commonly associated with NF-κB activation. Our study aimed to investigate whether VD could protect against OA by modulating NF-κB pathway and to explore the underlying mechanisms.</p> Methods <p>Proteins levels were assessed by western blot analysis, gene expression was quantified by quantitative real-time polymerase chain reaction (qRT‒PCR) in vivo and in vitro. The expression of phosphorylated-p65 (p-p65) in knee OA rats was detected by immunohistochemistry, and an NF-κB nuclear translocation assay was validated in chondrocytes. Immunoprecipitation was employed to detect the interaction between NF-κB and vitamin D receptor (VDR) in vivo and in vitro. Small interfering RNA (Si-NF-κB and Si-VDR) transfection was used to investigate the role of NF-κB and VDR signaling pathway in knee OA rats under VD influence. Cartilage changes were visualized of knee OA rats using hematoxylin and eosin as well as safranin-O/fast green of staining.</p> Results <p>Our findings indicated that VD alleviates OA by inhibiting NF-κB&#xa0;pathway, which in turn reduces chondrocyte apoptosis and extracellular matrix (ECM) degradation. Further analysis revealed that VD primarily stabilizes NF-κB through the interaction of VDR and NF-κB, modulating the AMPK/mTOR signaling pathway to enhance autophagy and delay the progression of OA.</p> Conclusion <p>This study highlights the protective role of VD in OA by stabilization of NF-κB, mainly through the interaction between VDR and NF-κB. This interaction regulates the AMPK/mTOR signaling pathway, promoting autophagy and suggesting a potential therapeutic strategy for OA management.<Table Float="No" ID="Taba"> <tgroup cols="1"> <colspec align="left" colname="c1" colnum="1" /> <tbody> <row> <entry align="left" colname="c1"> <p><b> Key Points</b></p> </entry> </row> <row> <entry align="left" colname="c1"> <p>• <i>VD confers a protective effect on OA by primarily stabilizing NF-κB through the interaction between VDR and NF-κB, which in turn inhibits NF-κB phosphorylation and nuclear translocation</i>.</p> <p>• <i>In chondrocytes, VD helps shield against OA by blocking NF-κB’s entry into the nucleus, subsequently regulating autophagy via the AMPK/mTOR signaling pathway</i>.</p> </entry> </row> </tbody> </tgroup> </Table></p>

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1,25(OH)2D3 induces chondrocyte autophagy and reduces the loss of proteoglycans in osteoarthritis through inhibiting the NF-κB pathway

  • 期刊论文

  • 发表日期：

    2025年1月7日

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  • Pingping Liu,
  • Junxian Zhou,
  • Haigang Cui,
  • Jianhua Xu,
  • Guangfeng Ruan,
  • Changhai Ding,
  • Kang Wang

摘要

Objective

Nuclear transcription factor-κB (NF-κB) activation is a pivotal event in the pathogenesis of osteoarthritis (OA). OA patients frequently exhibit vitamin D (VD) deficiency, which is commonly associated with NF-κB activation. Our study aimed to investigate whether VD could protect against OA by modulating NF-κB pathway and to explore the underlying mechanisms.

Methods

Proteins levels were assessed by western blot analysis, gene expression was quantified by quantitative real-time polymerase chain reaction (qRT‒PCR) in vivo and in vitro. The expression of phosphorylated-p65 (p-p65) in knee OA rats was detected by immunohistochemistry, and an NF-κB nuclear translocation assay was validated in chondrocytes. Immunoprecipitation was employed to detect the interaction between NF-κB and vitamin D receptor (VDR) in vivo and in vitro. Small interfering RNA (Si-NF-κB and Si-VDR) transfection was used to investigate the role of NF-κB and VDR signaling pathway in knee OA rats under VD influence. Cartilage changes were visualized of knee OA rats using hematoxylin and eosin as well as safranin-O/fast green of staining.

Results

Our findings indicated that VD alleviates OA by inhibiting NF-κB pathway, which in turn reduces chondrocyte apoptosis and extracellular matrix (ECM) degradation. Further analysis revealed that VD primarily stabilizes NF-κB through the interaction of VDR and NF-κB, modulating the AMPK/mTOR signaling pathway to enhance autophagy and delay the progression of OA.

Conclusion

This study highlights the protective role of VD in OA by stabilization of NF-κB, mainly through the interaction between VDR and NF-κB. This interaction regulates the AMPK/mTOR signaling pathway, promoting autophagy and suggesting a potential therapeutic strategy for OA management.

Key Points

• VD confers a protective effect on OA by primarily stabilizing NF-κB through the interaction between VDR and NF-κB, which in turn inhibits NF-κB phosphorylation and nuclear translocation.

• In chondrocytes, VD helps shield against OA by blocking NF-κB’s entry into the nucleus, subsequently regulating autophagy via the AMPK/mTOR signaling pathway.