Growth factors are polypeptides known to affect the growth and differentiated function of skeletal and nonskeletal cells. Skeletal cells synthesize a variety of growth factors, and insulin-like growth factor (IGF) I and II are among the most prevalent factors synthesized by these cells (Canalis et al., 1991). IGF I and II, polypeptides with an approximate molecular mass of 7600, regulate a variety of metabolic functions in skeletal and nonskeletal cells (Daughaday and Rotwein 1989). IGF I and II have similar biological activities although in bone cells IGF I is somewhat more potent than IGF II. IGFs stimulate the replica&m of cells of the osteoblastic lineage, likely preosteoblasts and stimulate collagen synthe&s and matrix apposition rates (Hock et al., 1988). The effect on matrix synthesis is independent from IGF actions on cell replication, and it appears to be secondary to an increase in type I collagen transcription by the osteoblast (McCarthy et al., 1989a). IGFs also decrease collagen degradation by mechanisms that are still unknown, and IGF I, but not IGF II, enhances the recruitment of bone resorbing cells, likely osteoclasts (Mochizuki et al., 1992). It is therefore apparent that IGFs have important actions on cells of the skeletal system and as such they are considered essential regulators of bone remodeling.

IGFs are present in the systemic circulation, where they sre bound to IGF’binding proteins (IGFBP) and to an acid labile subunit, forming a large molecular weight complex. IGFs are also secreted by a variety of skeletal and nonskeletal cell systems and are considered to act as systemic and local regulators of cell growth. The ‘mechanisms controlling the production of systemic and local IGF I sre likely different. Systemic IGF I is primarily derived from liver cells and it is under growth hormone control, whereaslocally produced I= I is controlled by a variety of hormones and growth factors which differ in various c&l systems.