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

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.
Authors	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, Yingfang Ao
Journal	Nature communications (Nat Commun) Vol. 10 Issue 1 Pg. 1914 (04 23 2019) ISSN: 2041-1723 [Electronic] England
PMID	31015473 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References	Anti-Inflammatory Agents Benzamides Cytokines Free Radical Scavengers Immunologic Factors N-((5-bromo-2-thienyl)sulfonyl)-2,4-dichlorobenzamide Sulfonamides Superoxides Sod3 protein, rat Superoxide Dismutase
Topics	Animals Anti-Inflammatory Agents (pharmacology) Benzamides (pharmacology) Cartilage, Articular (drug effects, immunology, pathology) Chondrocytes (drug effects, immunology, pathology) Cytokines (genetics, immunology) Disease Models, Animal Disease Progression Extracellular Matrix (drug effects, immunology, pathology) Free Radical Scavengers (pharmacology) Gene Expression Profiling Gene Expression Regulation Humans Immunologic Factors (pharmacology) Injections, Intra-Articular Male Osteoarthritis (drug therapy, genetics, immunology, pathology) Primary Cell Culture Rats Rats, Sprague-Dawley Sulfonamides (pharmacology) Superoxide Dismutase (genetics, immunology) Superoxides (antagonists & inhibitors, metabolism) Transcriptome (immunology)

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.

Realize the full power of the drug-disease research graph!