A small molecule promotes cartilage extracellular matrix generation and inhibits osteoarthritis development

Yuanyuan Shi, Xiaoqing Hu, Jin Cheng, Xin Zhang, Fengyuan Zhao, Weili Shi, Bo Ren, Huilei Yu, Peng Yang, Zong Li, Qiang Liu, Zhenlong Liu, Xiaoning Duan, Xin Fu, Jiying Zhang, Jianquan Wang () and Yingfang Ao ()
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Yuanyuan Shi: Peking University Third Hospital
Xiaoqing Hu: Peking University Third Hospital
Jin Cheng: Peking University Third Hospital
Xin Zhang: Peking University Third Hospital
Fengyuan Zhao: Peking University Third Hospital
Weili Shi: Peking University Third Hospital
Bo Ren: Peking University Third Hospital
Huilei Yu: Peking University Third Hospital
Peng Yang: Peking University Third Hospital
Zong Li: Peking University Third Hospital
Qiang Liu: Peking University Third Hospital
Zhenlong Liu: Peking University Third Hospital
Xiaoning Duan: Peking University Third Hospital
Xin Fu: Peking University Third Hospital
Jiying Zhang: Peking University Third Hospital
Jianquan Wang: Peking University Third Hospital
Yingfang Ao: Peking University Third Hospital

Nature Communications, 2019, vol. 10, issue 1, 1-14

Abstract: Abstract Degradation of extracellular matrix (ECM) underlies loss of cartilage tissue in osteoarthritis, a common disease for which no effective disease-modifying therapy currently exists. Here we describe BNTA, a small molecule with ECM modulatory properties. BNTA promotes generation of ECM components in cultured chondrocytes isolated from individuals with osteoarthritis. In human osteoarthritic cartilage explants, BNTA treatment stimulates expression of ECM components while suppressing inflammatory mediators. Intra-articular injection of BNTA delays the disease progression in a trauma-induced rat model of osteoarthritis. Furthermore, we identify superoxide dismutase 3 (SOD3) as a mediator of BNTA activity. BNTA induces SOD3 expression and superoxide anion elimination in osteoarthritic chondrocyte culture, and ectopic SOD3 expression recapitulates the effect of BNTA on ECM biosynthesis. These observations identify SOD3 as a relevant drug target, and BNTA as a potential therapeutic agent in osteoarthritis.

Date: 2019
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DOI: 10.1038/s41467-019-09839-x

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