Cartilage morphogenesis: role of bone and cartilage morphogenetic proteins, homeobox genes and extracellular matrix.

Cartilage morphogenesis is one of the central topics in skeletal development. Cartilage geometry determines the future architecture of bones, joints and associated ligaments and tendons. Recent progress in this area has come from purification, cloning and expression of genes encoding bone and cartilage morphogenetic proteins (BMPs and CDMPs). BMPs initiate de novo cartilage and bone differentiation. BMPs are a family of pleiotropic signals for progenitor cell migration by chemotaxis, proliferation, and differentiation. Very recently another class of related morphogenetic proteins, CDMPs have been isolated and cloned. CDMPs may be critical for mesenchymal condensation prior to overt cartilage differentiation, the first step in morphogenesis of both cartilage and bone. The cartilage morphogenetic cascade is a cellular and molecular continuum driven by regulatory signalling molecules such as BMPs and CDMPs and their receptors, homeobox genes, transcription factors, and finally the synthesis and supramolecular assembly of structural macromolecules of the extracellular matrix. BMPs and CDMPs bind to heparin, heparan sulfates, and collagens I and IV. Thus there is a symbiosis of regulatory and structural macromolecules in the morphogenesis of cartilage. An avalanche of recent advances from seemingly disparate areas bodes well for the complete elucidation of the molecular basis of morphogenesis of cartilage, the architectural blue-print for the skeleton.