EFFECTS OF RECOMBINANT HUMAN BONE MORPHOGENETIC PROTEIN-2 ON HUMAN BONE-MARROW CELLS CULTURED WITH VARIOUS BIOMATERIALS

Recombinant human bone morphogenetic protein-2 (rhBMP-2) is known to i nduce orthotopic and ectopic bone formation in vivo. Several in vitro studies using rat or mouse clonal cell lines have shown that rhBMP-2 m ay be involved in the differentiation of osteoblasts from osteoblast p recursor cells or stromal cells in the bone marrow. However, there is little information available about the effects of rhBMP-2 on cultured human bone marrow cells. We investigated the effects of rhBMP-2 cultur ed on human bone marrow cells and osteoblastic cells on various biomat erials. Human bone cells were divided into fresh bone marrow cells, fi broblast colony-forming units (cfu-F, stromal precursors), and osteobl astic cells. The cells were cultured with or without rhBMP-2 on variou s biomaterials, including titanium alloy, pure titanium, cobalt alloy, and hydroxyapatite. It was found that rhBMP-2 (500 ng/mL) significant ly stimulated alkaline phosphatase production by fresh bone marrow cel ls and cfu-F. However, when cultured on titanium alloy or pure titaniu m, only fresh bone marrow cells showed an increase of alkaline phospha tase production after rhBMP-2 stimulation. Production of osteocalcin, a marker of mature osteoblasts, was not stimulated by rhBMP-2 in any c ombinations tested. These findings suggest that rhBMP-2 may be involve d in inducing the differentiation of osteoblast precursor cells into o steoblastic cells rather than stimulating further differentiation of o steoblastic cells into mature osteoblasts. In addition, grafts of fres h human bone marrow cells of cfu-F stimulated by rhBMP-2 may have the potential to promote bone formation at sites of nonunion as well as ar ound titanium joint prostheses. (C) 1997 John Wiley & Sons, Inc.