ROCK inhibition enhances aggrecan deposition and suppresses matrix metalloproteinase-3 production in human articular chondrocytes

摘要: Homeostasis of articular cartilage is maintained by a balance between catabolism and anabolism. Matrix metalloproteinase-3 (MMP-3) cartilaginous extracellular matrix (ECM), including aggrecan (AGN), an important factor in osteoarthritis progression. We previously reported that inhibition Rho-associated coiled-coil forming kinase (ROCK), effector Rho family GTPases, activates the chondrogenic transcription SRY-type high-mobility-group box (SOX) 9 prevents dedifferentiation monolayer-cultured chondrocytes. hypothesized ROCK chondrocyte altering transcriptional MMP-3 AGN. Normal human chondrocytes were cultured presence or absence inhibitor (ROCKi, Y-27632). Expression AGN during monolayer cultivation was assessed quantitative real-time PCR western blot analysis. Chondrogenic redifferentiation potential ROCKi-treated evaluated immunohistological analysis pellet cultures. ROCKi treatment suppressed expression monolayer- pellet-cultured but increased expression. Chromatin immunoprecipitation revealed association factors E26 transformation specific (ETS)-1 SOX9 their target genes AGN, respectively, affected treatment. decreased ETS-1 its binding sites on promoter, whereas promoted interaction promoter. Our results suggest may have role modulating degradation synthesis ECM, finding facilitate development techniques to prepare differentiated for regeneration therapy.