Distribution of platelet-derived growth factor (PDGF) A chain mRNA, protein, and PDGF-alpha receptor in rapidly...

Platelet-derived growth factors (PDGFs) are potent bone cell mitogens which stimulate the proliferation of osteoblastic cells, may also be involved in the regulation of osteoclastic bone resorption, and indirectly induce vascular endothelial cell proliferation and angiogenesis. In view of the established relationship between angiogenesis and osteogenesis, the production of PDGFs by both osteoblastic and vascular endothelial cells suggests that they may play a role in bone formation during skeletal development. We have used two human models of rapid bone formation, heterotopic bone and osteophytic bone, to investigate the expression of PDGF-A mRNA and protein and the PDGF-alpha receptor protein in vivo using in situ hybridization and immunohistochemistry. PDGF-A mRNA and protein were widely distributed throughout heterotopic and osteophytic bone. Within the cartilaginous tissue PDGF-A mRNA and protein were most strongly expressed by mature chondrocytes with decreased expression in the hypertrophic zone and almost no staining in the mineralizing and mineralized zones. PDGF mRNA and protein were also expressed in cells of small blood vessels within fibrous and cartilaginous tissue. In contrast, PDGF-alpha receptor expression was restricted to a minority of hypertrophic chondrocytes and sites of vascular invasion. Within the bone and fibrous tissue the growth factor and the receptor were widely distributed, being detected on most cells at sites of bone formation or in remodeling sites; no receptor was detected on osteoclasts. These data demonstrate the widespread expression of PDGF-A and its receptor in forming human bone and indicate that this growth factor may exert autocrine and paracrine effects to regulate osteogenesis during skeletal development.