Open AccessOxymatrine exerts protective effects on osteoarthritis via modulating chondrocyte homoeostasis and suppressing osteoclastogenesis
Author(s) -
Jiang Yafei,
Sang Weilin,
Wang Cong,
Lu Haiming,
Zhang Tao,
Wang Zhuoying,
Liu Yu,
Xue Bao,
Xue Song,
Cai Zhengdong,
Hua Yingqi,
Zhu Libo,
Ma Jinzhong
Publication year - 2018
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/jcmm.13674
Subject(s) - chondrocyte , osteoarthritis , osteoclast , rankl , cartilage , bone resorption , in vivo , chemistry , oxymatrine , pharmacology , cancer research , medicine , microbiology and biotechnology , in vitro , pathology , receptor , anatomy , activator (genetics) , biochemistry , biology , alternative medicine
Osteoarthritis ( OA ) is a common degenerative disease characterized by the progressive destruction both articular cartilage and the subchondral bone. The agents that can effectively suppress chondrocyte degradation and subchondral bone loss are crucial for the prevention and treatment of OA . Oxymatrine ( OMT ) is a natural compound with anti‐inflammatory and antitumour properties. We found that OMT exhibited a strong inhibitory effect on LPS ‐induced chondrocyte inflammation and catabolism. To further support our results, fresh human cartilage explants were treated with LPS to establish an ex vivo degradation model, and the results revealed that OMT inhibited the catabolic events of LPS ‐stimulated human cartilage and substantially attenuated the degradation of articular cartilage ex vivo. As subchondral bone remodelling is involved in OA progression, and osteoclasts are a unique cell type in bone resorption, we investigated the effects of OMT on osteoclastogenesis, and the results demonstrated that OMT suppresses RANKL ‐induced osteoclastogenesis by suppressing the RANKL ‐induced NFAT c1 and c‐fos signalling pathway in vitro. Further, we found that the anti‐inflammatory and anti‐osteoclastic effects of oxymatrine are mediated via the inhibition of the NF ‐κB and MAPK pathways. In animal studies, OMT suppressed the ACLT ‐induced cartilage degradation, and TUNEL assays further confirmed the protective effect of OMT on chondrocyte apoptosis. Micro CT analysis revealed that OMT had an attenuating effect on ACLT ‐induced subchondral bone loss in vivo. Taken together, these results show that OMT interferes with the vicious cycle associated with OA and may be a potential therapeutic agent for abnormal subchondral bone loss and cartilage degradation in osteoarthritis.