Baicalin promotes chondrocyte viability and the synthesis of extracellular matrix through TGF-β/Smad3 pathway in chondrocytes

Background: Osteoarthritis (OA) is common in the elderly. Baicalin (BA) is a flavonoid monomer extracted from Scutellaria baicalensis Georgi, which has been reported to have anti-inflammatory, anti-deformation and anti-bacterial effects. Methods: Cultures of micromass and 3D alginate beads, Alcian blue and Safranin O (SO)/fast green staining were used to investigate chondrocyte viability and extracellular matrix (ECM) synthesis in chondrocytes of all groups. The expression of SOX9, Smad3, Aggrecan (ACAN), type II collagen (Col2 alpha), matrix metallopetidase 9 (MMP9), MMP13 and ADAMTS5 in chondrocytes of all groups were detected by western blot or qRT-PCR. Results: The present study demonstrates that BA neutralized the IL-1 beta-induced downregulation of chondrocyte viability and ECM secretion, including ACAN and Col2 alpha. The downregulation of SOX9, and the upregulation of MMP9, MMP13 and ADAMTS5 induced by IL-1 beta were reversed by BA treatment. Moreover, BA increased the nuclear translocation of Smad3 and SOX9 in chondrocytes cultured by micromass and 3D alginate beads. Interestingly, Smad3 inhibitor SIS3 reversed the promoting effect of BA on chondrocyte viability, ECM secretion, SOX9 and Smad3 nuclear translocation, and the inhibiting effect of BA on MMP9 and ADAMTS5 expressions. BA treatment also attenuated the decrease of Smad3 phosphorylation, SOX9 expression and the damage of cartilage integrity in mice which were induced by destabilization of the medial meniscus (DMM). Conclusion: BA promotes chondrocyte viability and the cell matrix synthesis through TGF-beta/Smad3 pathway in IL-1 beta-treated chondrocytes and DMM treated mice. BA is a potential therapeutic target for OA.