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Fracture repair requires the involvement of osteoclasts (OC), multinucleated cells which are responsible for bone resorption and form by fusion 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 circulating human OC precursor, and to determine the role bone stromal cells and humoral factors play in the differentiation of OCs, we co-cultured human umbilical cord blood monocytes with UMR106.01 osteoblast-like cells in the presence and absence of 1,25 dihydroxyvitamin D3 [1,25 (OH)2D3], macrophage-colony stimulating factor (M-CSF) and dexamethasone on both bone slices and coverslips. Isolated cells were positive only for monocyte/macrophage markers (CD11a, CD11b, CD14 and HLA-DR) and negative for OC markers [tartrate resistant acid phosphatase (TRAP), vitronectin receptors (VNR) and calcitonin receptors (CT receptors)] and did not form resorption pits on bone slices after 24 hr in culture. However, after 14 days in co-culture with UMR106.01 cells, in the presence of 1,25 (OH)2D3 and M-CSF, numerous TRAP, CT receptor and VNR positive multinucleated cells capable of extensive lacunar bone resorption were formed in these co-cultures. The presence of 1,25 (OH)2D3, 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 is vitro model of human OC differentiation should prove useful in further analysing factors controlling OC generation in bone remodelling and repair.

Original publication

DOI

10.1016/s1357-2725(96)00129-x

Type

Journal article

Journal

The international journal of biochemistry & cell biology

Publication Date

01/1997

Volume

29

Pages

173 - 179

Addresses

University of Oxford, Nuffield Department of Pathology and Bacteriology, John Radcliffe Hospital, Oxford, U.K.

Keywords

Monocytes, Cells, Cultured, Cell Line, Osteoclasts, Osteoblasts, Fetal Blood, Animals, Humans, Rats, Bone Resorption, Calcitriol, Macrophage Colony-Stimulating Factor, Receptors, Calcitonin, Histocytochemistry, Cell Differentiation, Pregnancy, Female