Rhoifolin ameliorates osteoarthritis via the Nrf2/NF-κB axis: in vitro and in vivo experiments

Objective: Osteoarthritis (OA) is an age-related degenerative disease accompanied by an increasing number of senescent cells and chronic low-grade inflammation. Rhoifolin (ROF) showed considerable inhibition to inflammation, but its role in chondrocyte senescence and OA progress has not been fully characterized. We aimed to evaluate the protective effects of ROF on OA through a series of in vitro and in vivo experiments. Methods: The role of ROF in the expression of senescence-associated secretory phenotype (SASP) factors was investigated using RT-qPCR, western blotting, and ELISA. Chondrocyte senescence was assessed by SA-beta-gal staining. We applied molecular docking to screen candidate proteins regulated by ROF. Meanwhile, SASP factors and cellular senescence were further assessed after the transfection of Nrf2 siRNA. In the anterior cruciate ligament transection (ACLT) rat model, X-ray, hematoxylin-eosin (HE), and Masson's staining were performed to evaluate the therapeutic effects of ROF on OA. Results: We found that ROF inhibited SASP factors expression and senescence phenotype in IL-1 beta-treated chondrocytes. Furthermore, ROF suppressed IL-1 beta-induced activation of the NF-kappa B pathway cascades. Also, molecular docking and knock-down studies demonstrated that ROF might bind to Nrf2 to suppress the NF-kappa B pathway. In vivo, ROF ameliorated the OA process in the ACLT rat model. Conclusions: ROF inhibits SASP factors expression and senescence phenotype in chondrocytes and ameliorates the progression of OA via the Nrf2/NF-kappa B axis, which supports ROF as a potential therapeutic agent for the treatment of OA. (C) 2022 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

Automated summary

The study shows that ROF inhibits the expression of inflammatory factors and chondrocyte senescence, improves the progression of OA through the Nrf2/NF-κB axis, and has potential as a therapeutic agent for OA.