RODENT OSTEOBLAST-LIKE CELLS SUPPORT OSTEOCLASTIC DIFFERENTIATION OF HUMAN CORD-BLOOD MONOCYTES IN THE PRESENCE OF M-CSF AND 1,25-DIHYDROXYVITAMIN D-3

Fracture repair requires the involvement of osteoclasts (OC), multinuc leated cells which are responsible for bone resorption and form by fus ion of circulating mononuclear haemopoietic precursors. The nature of these circulating precursor cells, in particular their relationship to blood monocytes, is uncertain. To define further the nature of the ci rculating human OC precursor, and to determine the role bone stromal c ells and humoral factors play in the differentiation of OCs, we co-cul tured human umbilical cord blood monocytes with UMR106.01 osteoblast-l ike cells in the presence and absence of 1,25 dihydroxyvitamin D-3 [1, 25(OH)(2)D-3], macrophage-colony stimulating factor (M-CSF) and dexame thasone on both bone slices and coverslips. Isolated cells were positi ve only for monocyte/macrophage markers (CD11a, CD11b, CD14 and HLA-DR ) and negative for OC markers [tartrate resistant acid phosphatase (TR AP), vitronectin receptors (VNR) and calcitonin receptors (CT receptor s)] and did not form resorption pits on bone slices after 24 hr in cul ture. However, after 14 days in co-culture with UMR106.01 cells, in th e presence of 1,25 (OH)(2)D-3 and M-CSF, numerous TRAP, CT receptor an d VNR positive multinucleated cells capable of extensive lacunar bone resorption were formed in these co-cultures. The presence of 1,25 (OH) (2)D-3, M-CSF and a bone-derived stromal cell population were absolute requirements for OC differentiation. It is concluded that mononuclear phagocytes are capable of differentiating into mature functional OCs when cultured under specific cellular and hormonal conditions. This in vitro model of human OC differentiation should prove useful in furthe r analysing factors controlling OC generation in bone remodelling and repair. (C) 1997 Elsevier Science Ltd. All rights reserved.