Liquiritin reduces chondrocyte apoptosis through P53/PUMA signaling pathway to alleviate osteoarthritis.

The main pathological features of osteoarthritis (OA) include the degeneration of articular cartilage and a decrease in matrix synthesis. Chondrocytes, which contribute to matrix synthesis, play a crucial role in the development of OA. Liquiritin, an effective ingredient extracted from Glycyrrhiza uralensis Fisch., has been used for over 1000 years to treat OA. This study aims to investigate the impact of liquiritin on OA and its underlying mechanism. Gait and hot plate tests assessed mouse behavior, while Micro-CT and ABH/OG staining observed joint morphological changes. The TUNEL kit detected chondrocyte apoptosis. Western blot and immunofluorescence techniques determined the expression levels of cartilage metabolism markers COL2 and MMP13, as well as apoptosis markers caspase3, bcl2, P53, and PUMA. KEGG analysis and molecular docking technology were used to verify the relationship between liquiritin and P53. Liquiritin alleviated pain sensitivity and improved gait impairment in OA mice. Additionally, we found that liquiritin could increase COL2 levels and decrease MMP13 levels both in vivo and in vitro. Importantly, liquiritin reduced chondrocyte apoptosis induced by OA, through decreased expression of caspase3 expression and increased expression of bcl2 expression. Molecular docking revealed a strong binding affinity between liquiritin and P53. Both in vivo and in vitro studies demonstrated that liquiritin suppressed the expression of P53 and PUMA in cartilage. This indicated that liquiritin may alleviate OA progression by inhibiting the P53/PUMA signaling pathway, suggesting that liquiritin is a potential strategy for the treatment of OA. Copyright © 2024. Published by Elsevier Inc.

Citation

Min Qiu, Liangyan Cheng, Jianbo Xu, Minwei Jin, Wenhua Yuan, Qinwen Ge, Kaiao Zou, Jiali Chen, Yuliang Huang, Ju Li, Liming Zhu, Bing Xu, Chunchun Zhang, Hongting Jin, Pinger Wang. Liquiritin reduces chondrocyte apoptosis through P53/PUMA signaling pathway to alleviate osteoarthritis. Life sciences. 2024 Apr 15;343:122536

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PMID: 38423170

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