REGULATION OF PROLIFERATION AND OSTEOCHONDROGENIC DIFFERENTIATION OF PERIOSTEUM-DERIVED CELLS BY TRANSFORMING GROWTH-FACTOR-BETA AND BASIC FIBROBLAST GROWTH-FACTOR

We studied the effects of transforming growth factor-beta and basic fibroblast growth factor on the regulation of proliferation and osteochondrogenic differentiation of periosteum-derived cells, which have the potential to differentiate into bone and hypertrophic cartilage in vitro. Histological observation revealed that transforming growth factor-beta stimulated chondrogenesis of periosteum-derived cells while basic fibroblast growth factor stimulated proliferation of fibroblast-like cells and inhibited osteochondrogenic differentiation. Immunohistochemical studies revealed that basic fibroblast growth factor inhibited the expression of osteocalcin. Transforming growth factor-beta enhanced uronic acid content but decreased DNA content, alkaline phosphatase activity, and calcium content. In contrast, basic fibroblast growth factor enhanced DNA content but decreased alkaline phosphatase activity, calcium content, and uronic acid content. In addition, transforming growth factor-beta shortened the time-course of gene expression of type-X collagen whereas basic fibroblast growth factor inhibited the gene expression, These results indicate that transforming growth factor-beta stimulates osteochondrogenic differentiation of periosteum-derived cells but inhibits proliferation. They also indicate that basic fibroblast growth factor stimulates proliferation of periosteum-derived cells but inhibits osteochondrogenic differentiation. CLINICAL RELEVANCE: These observations suggest that both transforming growth factor-beta and basic fibroblast growth factor are involved in the regulation of bone growth, fracture-healing, and callus distraction, processes in which the periosteum plays a crucial role. Transforming growth factor-beta stimulates periosteal cytodifferentiation into hypertrophic chondrocytes. In contrast, basic fibroblast growth factor stimulates the mitotic activity of periosteal mesenchymal cells at the expense of their osteochondrogenic differentiation. Additional studies are needed to clarify the interaction and combined effect of these two growth factors and of others and to develop their clinical application in vivo to enhance bone regulation in fracture-healing and in bone-lengthening by callus distraction.