The human osteoclast precursor circulates in the monocyte fraction.

Abstract

The osteoclast is known to be formed by fusion of circulating mononuclear precursor cells of haematopoietic origin. The precise nature of these circulating cells and, in particular, their relation to monocytes is unknown. We have developed an in vitro system of human osteoclast formation whereby human monocytes [CD14, CD11a, CD11b and HLA-DR positive, and tartrate-resistant acid phosphatase (TRAP), calcitonin receptor (CTR), vitronectin receptor (VNR) negative] were isolated and cocultured for up to 21 days with UMR106 rat osteoblast-like cells or ST2 mouse preadipocytic bone marrow stromal cells in the presence of 1 alpha, 25 dihydroxyvitamin D3 (1,25(OH)2D3) and macrophage colony stimulating factor (M-CSF). Numerous TRAP, VNR and CTR positive multinucleated cells, capable of extensive lacunar bone resorption, formed in these cocultures; the absolute requirements for this to occur were contact with the above bone stromal cells, 1,25(OH)2D3, and M-CSF. These results show that the human mononuclear osteoclast precursor circulates in the monocyte fraction and exhibits a monocyte phenotype, acquiring osteoclast phenotypic features in the process of differentiation into mature functional osteoclasts.

Interleukin-1.BETA. Stimulates Transendothelial Mobilization of Human Peripheral Blood Mononuclear Cells with a Potential to Differentiate into Osteoclasts in the Presence of Osteoblasts.

“…A previous study [3] suggested that osteoclast precursors are present in the circulation of osteopetrotic mice. Moreover, avian [4], murine [5,6] and human [7][8][9] monocytes in the peripheral blood can differentiate into osteoclast-like cells.…”

Characterization of circulating osteoblast lineage cells in humans

“…Osteoclast precursors had clearly been shown to be present in peripheral blood [11]; while circulating osteoblast precursors, identified on the basis of adherence to plastic, had also been found by several groups [12,13], the concentration of these cells was extremely low (~1 in 10 8 mononuclear cells [MNCs] or less in humans) [13]. We reasoned that plastic adherence may well have underestimated the concentration of these cells in peripheral blood, and using flow cytometry following staining with OCN or AP antibodies, recently demonstrated that OCN pos or AP pos cells were indeed present in the peripheral blood in humans, constituting ~1% of circulating MNCs [14].…”

VEGF, FLT3 ligand, PlGF and HGF can substitute for M-CSF to induce human osteoclast formation: implications for giant cell tumour pathobiology

“…1,2 It exhibits a number of specialised cytochemical and functional features, including the ability to carry out lacunar bone resorption. Increased osteoclast formation and activity is seen in a number of osteolytic bone and joint conditions, including notably giant cell tumour of bone (GCTB), a primary bone tumour, which contains numerous, very large, often hyper-nucleated osteoclastic giant cells that effect a considerable amount of bone resorption.…”