Tangeretin suppresses osteoarthritis progression via the Nrf2/NF-κB and MAPK/NF-κB signaling pathways

橘皮素通过 Nrf2/NF-κB 和 MAPK/NF-κB 信号通路抑制骨关节炎进展

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作者:Yifeng Shi, Jiaoxiang Chen, Sunlong Li, Yuhao Wu, Caiyu Yu, LiBin Ni, Jian Xiao, Zhenxuan Shao, Huanqing Zhu, Jianshun Wang, Xiangyang Wang, Xiaolei Zhang

Background

Osteoarthritis (OA) is a globally prevalent degenerative disease characterized by extracellular matrix (ECM) degradation and inflammation. Tangeretin is a natural flavonoid that has anti-inflammatory properties. Studies have not explored whether tangeretin modulates OA development.

Conclusion

Tangeretin abrogates OA progression by inhibiting inflammation as well as ECM degradation in chondrocytes and animal models. Effects of tangeretin are mediated through Nrf2/NF-κB and the MAPK/NF-κB pathways. Thus, tangeretin is a potential therapeutic agent for osteoarthritis treatment.

Methods

Protective effects of tangeretin on murine articular chondrocytes treated with interleukin-1β (IL-1β) were evaluated using qPCR, western blot analysis, ELISA, ROS detection and immunofluorescent staining in vitro. Healing effect of tangeretin on cartilage degradation in mice was assessed through X-ray imaging, histopathological analysis, immunohistochemical staining and immunofluorescent staining in vivo.

Purpose

The aim of this study was to explore the potential effects and mechanism underlying the anti-OA properties of tangeretin. Study design: Effects of tangeretin on OA were detected in chondrocytes and OA mouse model.

Results

Tangeretin suppressed IL-1β-mediated inflammatory mediator secretion and degradation of ECM in chondrocytes. The results showed that tangeretin abrogated destabilized medial meniscus (DMM)-induced cartilage degradation in mice. Mechanistic studies showed that tangeretin suppressed OA development by downregulating activation of NF-κB by activating Nrf2/HO-1 axis and suppressing MAPK signaling pathway.

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