Indole-3-propionic acid alleviates chondrocytes inflammation and osteoarthritis via the AhR/NF-κB axis

Molecular Medicine

Research Article

Huangming Zhuang¹  Xunshan Ren¹  Panghu Zhou¹  Fuze Jiang¹ 

[1] Department of Orthopedics, Renmin Hospital of Wuhan University, 430060, Wuhan, China;

关键词: Indole-3-propionic acid;    Osteoarthritis;    Aromatic hydrocarbon receptor;    Chondrocytes;    Inflammation;   

DOI  :  10.1186/s10020-023-00614-9

 received in 2022-10-07, accepted in 2023-01-23,  发布年份 2023

来源: Springer

【 摘 要 】

BackgroundOsteoarthritis (OA) is a common chronic disease characterized by chronic inflammation and extracellular matrix degradation. Indole-3-propionic acid (IPA) is a tryptophan metabolite secreted by intestinal flora, which can exert anti-inflammatory effects in a variety of diseases. In this study, we further investigated the potential therapeutic role of IPA in OA and the underlying mechanism.MethodsIL-1β was utilized to induce chondrocyte inflammation. Then, the cytotoxicity of IPA on rat chondrocytes was assessed. Meanwhile, RT-qPCR, Griess reaction, ELISA, Western blot and immunofluorescence were performed to evaluate the expression of inflammatory factors and stromal proteins, and the NF-κB pathway in chondrocytes treated with IL-1β alone, with IPA or with aryl hydrocarbon receptor (AhR) knockdown. An OA rat model was established by anterior cruciate ligament transection, and hematoxylin-eosin staining, Safranin-O/Fast Green staining and immunochemistry were applied to estimate OA severity.ResultsIPA did not affect cellular viability at concentrations up to 80 µM. IPA significantly inhibited the IL-1β-induced expression of inflammatory factors (Nitric oxide, PGE2, TNF-α, IL-6, iNOS and COX-2) and matrix-degrading enzymes (MMP-3, MMP-13 and ADAMTS-5), upregulated the expression of anabolic markers (aggrecan and collagen-II) and inactivated the NF-κB pathway. However, AhR knockdown could abolish the above protection capabilities and the suppression of the NF-κB pathway induced by IPA. Furthermore, IPA significantly reduced serum inflammatory cytokines expression, cartilage destruction and synovitis in vivo, demonstrating its protective role in OA progression.ConclusionIPA improved IL-1β-induced chondrocyte inflammation and extracellular matrix degradation through the AhR/NF-κB axis, which provides an innovative therapeutic strategy for OA.

【 授权许可】

CC BY   
© The Author(s) 2023

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