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

Author

Listed:
  • 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)

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.

Suggested Citation

  • 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 , 2019. "A small molecule promotes cartilage extracellular matrix generation and inhibits osteoarthritis development," Nature Communications, Nature, vol. 10(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-09839-x
    DOI: 10.1038/s41467-019-09839-x
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