Roles of Collagen Molecules in Growth and Differentiation of Human Osteoblasts

Collagen is the most abundant organic component of bone. It constitutes a superfamily of extracellular matrix proteins whose primary function is structural. The major collagenous component of bone is type I collagen, but types III, V, and X collagens are also found in bone tissue. Recently it was reported that collagen is essential for the growth and differentiation of various kinds of cell including osteoblasts. In order to investigate the function of the respective collagen components in the growth and differentiation of osteoblasts, we employed human osteoblast-like MG-63 cells and normal human osteoblasts, as well as human bone marrow stem cells; cultured them in the presence or absence of ascorbic acid 2-phosphate (Asc 2-P) and/or vitamin D3 (VD3); and examined the relationship between specific collagen types and the growth and differentiation of the cells. The stimulation of cell proliferation by the addition of Asc 2-P or epidermal growth factor is closely associated with an increase in the synthesis of type III collagen. The stimulation of osteoblast differentiation by the addition of VD3 resulted in growth retardation of the cells. The inhibition of type I or III collagen synthesis by adding the respective siRNAs attenuated the effects of these agents. Employing type I or III collagen as a substratum also regulated the growth and/or differentiation of human osteoblasts.This review reveals that type I and III collagens function as regulatory molecules for the differentiation and proliferation of human osteoblastic cells, and discusses the possibility that collagen metabolism is a possible new target for the treatment of osteoporosis.