Activation and dedifferentiation of chondrocytes: implications in cartilage injury and repair

Abstract

Cartilage injury remains a major challenge in orthopedic surgery due to the fact that articular cartilage has only a limited capacity for intrinsic healing. Cartilage impaction is followed by a post-traumatic inflammatory response. Chondrocytes and synoviocytes are activated to produce inflammatory mediators and degradative enzymes which can induce a progradient cartilage self-destruction finally leading to secondary osteoarthritis (OA). However, an anti-inflammatory compensatory response is also detectable in cartilage by up-regulation of anti-inflammatory cytokines, probably a temporary attempt by chondrocytes to restore cartilage homeostasis. Matrix-assisted autologous chondrocyte transplantation (MACT) is a suitable technique for improving the rate of repair of larger articular cartilage defects. For MACT, autologous chondrocytes were isolated from a cartilage biopsy of a non-load bearing joint area. This technique requires sufficient expansion of differentiated autologous chondrocytes, which were then seeded on suitable biodegradable three-dimensional (3D) matrices to preform an extracellular cartilage matrix (ECM) before implantation into the defect. Cell expansion is accompanied by chondrocyte dedifferentiation, whereby substantial changes occur at multiple levels of chondrocyte synthetic profiles: including the ECM, cell surface receptors and cytoskeletal proteins. Since these dedifferentiated chondrocytes produce a non-specific mechanically inferior ECM, they are not suitable for MACT. 3D cultures are means of inducing and maintaining chondrocyte (re)differentiation and to preform ECM. The combination of MACT with anabolic growth factors and anti-inflammatory strategies using anti-inflammatory mediators might be useful for stabilizing the differentiated chondrocyte phenotype, to support neocartilage formation and inhibit post-traumatic cartilage inflammation and hence, the development of secondary OA.