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Background  The previous studies indicated that CrmA could ameliorate the interleukin-1β induced osteoarthritis. In this study, we investigated the controlled-released cytokine response modifier A (CrmA) from hyaluronic acid (HA)-chitosan (CS) microspheres to improve interleukin-1β (IL-1β)-stimulated dedifferentiation of chondrocytes.    Methods  A rat model of osteoarthritis (OA) in vitro was established using 10 ng/ml IL-1β as modulating and chondrocytes inducing agent. HA-CS-CrmA microspheres were added to the medium after IL-1β was co-cultured with freshly isolated rat chondrocytes for 48 hours. The chondrocytes viability and glycosaminoglycan (GAG) content were determined. The level of CrmA secreted was detected by Enzyme-Linked Immunosorbent Assay (ELISA). The protein levels of type II collagen, aggrecan, collagen I and IL-1β were detected using western blotting analyses.    Results  The CrmA release kinetics were characterized by an initial burst release, which was reduced to a linear release over ten days. The production of GAG and the expression of type II collagen, aggrecan significantly increased compared with the control group, while the expression of collagen I and IL-1β decreased.    Conclusions  This study demonstrated that HA-CS microspheres containing CrmA could attenuate the degeneration of articular cartilage by maintaining the phenotype of chondrocytes during culture expansion. The suppression of inflammatory cytokines activity within the joint might be one important mechanism of the action of the microspheres in the treatment of OA.

Inhibition of interleukin-1beta-stimulated dedifferentiation of chondrocytes via controlled release of CrmA from hyaluronic acid-chitosan microspheres