TGFβ superfamily-dependent and osmolarity-mediated type II collagen expression by chondrocytes in vitro

摘要

Background:In vitro expansion of human articular chondrocytes (HACs) is required for cell-based therapies to treat cartilage pathologies, because cartilage has a poor intrinsic repair capacity. During standard expansion culture (i.e., plasma osmolarity, 280 mOsm/kg) chondrocytes inevitably lose their specific phenotype and de-differentiate. Unfortunately, this makes them inappropriate for autologous chondrocyte implantation, or related, chondral repair techniques. It has been shown that slightly elevated, but for articular chondrocytes physiological, osmolarity (i.e., 380 mOsm/kg) increases type II collagen (COL2) expression in vitro. The underlying molecular mechanism is, however, currently unknown. The transforming growth factor beta (TGFβ) superfamily members are accepted key regulators of chondrocyte differentiation and further well-known to stimulate COL2 synthesis in a variety of cell types, among which are chondrocytes. In this study, we aimed to elucidate the contribution of the TGFβ superfamily signalling as a putative molecular mechanism that potentially stimulates COL2 expression under physiological hyperosmolarity in vitro.