Human Osteoclast Formation from Blood Monocytes, Peritoneal Macrophages, and Bone Marrow Cells

Abstract

Mononuclear precursors of the human osteoclast have been identified in both bone marrow and the circulation in man, but osteoclast membership of the mononuclear phagocyte system (MPS) and its precise cellular ontogeny remain controversial. We isolated human hematopoietic marrow cells, blood monocytes, and peritoneal macrophages and incubated each of these cell populations with UMR106 osteoblast-like cells on glass coverslips and dentine slices in both the presence and absence of 1,25 dihydroxyvitamin D3 (1,25(OH)2D3), macrophage-colony stimulating factor (M-CSF), and dexamethasone. Cells isolated from peripheral blood and peritoneal dialysis fluid were positive only for monocyte/macrophage markers (CD11a, CD11b, CD14, and HLA-DR) and negative for osteoclast markers [tartrate-resistant acid phosphatase (TRAP), vitronectin reception (VNR), and calcitonin (CT) receptors and did not form resorption pits on dentine slices after 24 hours in culture. Similarly marrow cells did not form resorption pits on dentine slices after 24 hours in culture. However, after 14 days in co-culture with UMR106 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 resorption were formed in co-cultures of all these preparations. The presence of 1,25 (OH)2D3, M-CSF, and UMR106 were absolute requirements for osteoclast differentiation. It is concluded that precursor cells capable of osteoclast differentiation are present in the marrow compartment, the monocyte fraction of peripheral blood, and in the macrophage compartment of extraskeletal tissues and that these cells are capable of differentiating into mature functional osteoclasts. These findings argue in favor of osteoclast membership of the human MPS.

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.…”

Detection of significant pathways in osteoporosis based on graph clustering

“…These two functions are performed by osteoclasts. Osteoclasts are members of the monocyte/macrophage lineage and are formed by multiple instances of cellular fusion of their mononuclear precursors (5). Monocytes differentiate into osteoclasts in the presence of various molecular signals (6).…”

Prostate Cancer Promotes Cd11b Positive Cells to Differentiate Into Osteoclasts

“…Furthermore, prostate cancer cells have been demonstrated to secrete these factors that promote osteoclastogenesis of HBMCs [Lu et al, 2007]. The purpose of this study was to further delineate the cell -types and mechanisms involved in prostate cancer induced osteoclastogenesis.Monocyte-macrophages are known to be the precursors of osteoclasts [Fujikawa et al, 1996;Quinn et al, 1998]. The cell surface antigen CD11/CD18 is known to be a heterodimeric structure, consisting of a common β subunit (CD18) and a distinct β subunit (CD11a, CD11b, CD11c).…”

“…Monocyte-macrophages are known to be the precursors of osteoclasts [Fujikawa et al, 1996;Quinn et al, 1998]. The cell surface antigen CD11/CD18 is known to be a heterodimeric structure, consisting of a common β subunit (CD18) and a distinct β subunit (CD11a, CD11b, CD11c).…”