Peptide growth factors and their interactions during chondrogenesis

Peptide growth factors have been implicated in three aspects of cartilage growth and metabolism; the induction of mesoderm and differentiation of a cartilaginous skeleton in the early embryo, the growth and differentiation of chondrocytes within the epiphyseal growth plates leading to endochondral calcification, and the processes of articular cartilage damage and repair. Three peptide growth factor classes have been strongly implicated in these processes, the fibroblast growth factor family (FGF), the insulin-like growth factors (IGFs) including insulin, and transforming growth factor-beta (TGF-beta) and related molecules. Each of these peptide groups are expressed in the early embryo. Basic FGF, TGF-beta and the related activin have been shown to induce the appearance of mesoderm from primitive neuroectoderm. TGF-beta and related bone morphometric proteins can induce the differentiation of cartilage from primitive mesenchyme, and together with basic FGF and IGFs promote cartilage growth. Each class of growth factor is expressed within the epiphyseal growth plate where their autocrine/paracrine interactions regulate the rate of chondrocyte proliferation, matrix protein synthesis and terminal differentiation and mineralization. Basic FGF may prove useful in articular cartilage repair, while basic FGF, IGFs and TGF-beta are among a number of growth factors and cytokines that have been implicated in cartilage disease.