A small molecule promotes cartilage extracellular matrix generation and inhibits osteoarthritis development.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 31015473.
- Also identified by DOI 10.1038/s41467-019-09839-x and PMC identifier 6478911.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
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.
Medical subject headings
- Anti-Inflammatory Agents
- Benzamides
- Cartilage, Articular
- Extracellular Matrix
- Free Radical Scavengers
- Immunologic Factors
- Osteoarthritis
- Sulfonamides