REGULATION OF BONE-MATRIX PROTEIN EXPRESSION AND INDUCTION OF DIFFERENTIATION OF HUMAN OSTEOBLASTS AND HUMAN BONE-MARROW STROMAL CELLS BY BONE MORPHOGENETIC PROTEIN-2

We have examined the effects of BMP-2 on the expression of bone matrix proteins in both human bone marrow stromal cells (HBMSC) and human os teoblasts (HOB) and their proliferation and mineralization. Both HBMSC and HOB express BMP-2/-4 type I and type II receptors. Treatment of t hese two cell types with BMP-2 for 4 weeks in the presence of beta-gly cerophosphate and ascorbic acid results in mineralization of their mat rix. BMP-2 increases the mRNA level and activities of alkaline phospha tase and elevates the mRNA levels and protein synthesis of osteopontin , bone sialoprotein, osteocalcin, and alpha 1(I) collagen in both cell types. Whereas the mRNA level of decorin is increased, the mRNA conce ntration of biglycan is not altered by BMP-2. No effect on osteonectin is observed. The effect of BMP-2 on bone matrix protein expression is dose dependent from 25 to 100 ng/ml and is evident after 1-7 days tre atment. In the presence of BMP-2, proliferation of HBMSC and HOB is de creased under either serum-free condition or in the presence of serum. Thus, BMP-2 has profound effects on the proliferation, expression of most of the bone matrix proteins and the mineralization of both relati vely immature human bone marrow stromal preosteoblasts and mature huma n osteoblasts. (C) 1997 Wiley-Liss, Inc.