Requirement of autocrine signaling by bone morphogenetic protein-4 for chondrogenic differentiation of ATDC5 cells.

Mouse EC cell line ATDC5 undergoes differentiation to form cartilage nodules via the cellular condensation stage in the presence of insulin. ATDC5 cells expressed transcripts for bone morphogenetic protein-4 (BMP-4), and type IA and type II BMP receptors. Moreover, cells retained responsiveness to BMP-4, which induced the formation of chondrocytes in the culture. When transfected with a kinase domain-truncated type IA BMP receptor construct, cells failed to undergo differentiation beyond the condensation stage even in the presence of insulin. The soluble form of type IA BMP receptor also blocked the formation of chondrocytes in a dose dependent manner. These lines of evidence suggested that autocrine BMP-4 signaling is required for the conversion of chondrogenic precursor cells into chondrocytes.