Pseudolaric acid B ameliorates synovial inflammation and vessel formation by stabilizing PPARγ to inhibit NF-κB signalling pathway.
Pseudolaric acid B ameliorates synovial inflammation and vessel formation by stabilizing PPARγ to inhibit NF-κB signalling pathway.
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Pseudolaric Acid B 通过稳定 PPAR gamma 抑制 NF-kappa B 信号通路来改善滑膜炎症和血管形成
DOI：
10.1111/jcmm.16670
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发表时间：
2021-07
影响因子：
5.3
通讯作者：
Yu X
中科院分区：
文献类型：
--
作者：
Lu J;Guan H;Wu D;Hu Z;Zhang H;Jiang H;Yu J;Zeng K;Li H;Zhang H;Pan C;Cai D;Yu X
滑膜巨噬细胞极化和炎症在骨关节炎的发生发展中起重要作用，但其发病的分子机制和调控机制尚不清楚。在这里，我们报告了伪麻黄酸B(PAB)减轻骨关节炎时关节软骨退变和滑膜炎的作用。PAB是一种二萜酸，它特异性地抑制了NF-κB信号转导，减少了促炎细胞因子的产生，从而进一步减少了M1极化和血管形成。我们进一步提供了体内和体外证据，证明PAB通过稳定PPARκ而抑制了NF-γB信号转导。应用PPARγ拮抗剂可取消PAB的抗炎作用，挽救骨关节炎时NF-κB信号的激活。我们的发现确认了PAB在OA的调节中的作用，并提供了PAB通过PPARγ调节NF-PAB信号的机制，这进一步表明，在早期阶段靶向滑膜炎症或抑制血管形成可能是一种有效的预防策略。
Synovial macrophage polarization and inflammation are essential for osteoarthritis (OA) development, yet the molecular mechanisms and regulation responsible for the pathogenesis are still poorly understood. Here, we report that pseudolaric acid B (PAB) attenuated articular cartilage degeneration and synovitis during OA. PAB, a diterpene acid, specifically inhibited NF‐κB signalling and reduced the production of pro‐inflammatory cytokines, which further decreased M1 polarization and vessel formation. We further provide in vivo and in vitro evidences that PAB suppressed NF‐κB signalling by stabilizing PPARγ. Using PPARγ antagonist could abolish anti‐inflammatory effect of PAB and rescue the activation of NF‐κB signalling during OA. Our findings identify a previously unrecognized role of PAB in the regulation of OA and provide mechanisms by which PAB regulates NF‐κB signalling through PPARγ, which further suggest targeting synovial inflammation or inhibiting vessel formation at early stage could be an effective preventive strategy for OA.
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影响因子：
27.4
作者：
Atukorala I;Kwoh CK;Guermazi A;Roemer FW;Boudreau RM;Hannon MJ;Hunter DJ
通讯作者：
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影响因子：
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作者：
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作者：
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