The somatomedins are a family of low-molecular-weight peptides that are thought to mediate the stimulatory effect of growth hormone on skeletal growth. The cells that are directly responsible for skeletal growth are the chondrocytes of the epiphyseal growth plate, and these are the presumed skeletal target cells for somatomedin. As with other peptide growth factors, the cellular effects of the somatomedins are initiated by the interaction of the growth factor with specific receptors on target-cell surface membranes. Chondrocytes that have been isolated from bovine growth plates were previously found to possess specific surface receptors for the principal growth-hormone-dependent somatomedin, somatomedin-C. These studies indicated that the interaction of growth-plate chondrocytes with somatomedin-C involves specific receptor-binding followed by somatomedin-C internalization by the cell, a process identical to that identified in the mechanism of action of other peptide growth factors in other cells. These studies, however, left unanswered the questions of whether there are differences in binding of somatomedin-C by the different cell populations within the physis and whether somatomedin-C has access to cells in intact tissues. The current studies address these issues and indicate that bovine physeal chondrocytes in situ are accessible to exogenous somatomedin-C, that they specifically bind somatomedin-C in situ, and that cells of different physeal zones bind somatomedin-C differently. Labeled somatomedin-C is specifically bound by cells of all physeal zones. However, the binding is greatest for those cells undergoing active synthesis of DNA in the proliferative zone. Specific binding of somatomedin-C by cells in zones where cellular replicative activity is absent (for instance, the maturation and hypertrophic zones) indicates an uncoupling of the proliferative response to somatomedin-C and suggests that somatomedin-C may play a role in the differentiated functions of these cells. Clinical relevance: Normal skeletal growth depends on a complex and orderly sequence of division and maturation of the chondrocytes of the growth plate. An understanding of the regulation of this process is essential to an understanding of normal growth and of the pathophysiology of disorders of growth. The current studies suggest that the contribution of somatomedin-C to the regulation of growth is more complex than has been previously thought and may vary for different populations of cells within the physis. In addition, these studies provide an important baseline against which one may test the hypothesis that abnormal somatomedin-chondrocyte interactions are associated with disordered growth.
ASJC Scopus subject areas
- Orthopedics and Sports Medicine