Cell surface characterization of the human osteoclast: Phenotypic relationship to other bone marrow‐derived cell types

Abstract

Among the differentiated progeny of stem cells transplantable by bone marrow are osteoclasts, the multinucleate cells which are the major agents of bone resorption. Although the osteoclast is well characterized from a structural and functional standpoint, its development and origin are still far from clear. We have used monoclonal antibodies to investigate the interrelationship between osteoclasts and other haemopoietic cells in man. We have analysed the distribution of 19 granulocyte-monocyte antigens in eight reactivity clusters on the non-neoplastic osteoclasts present within nine osteoclastomas (syn. giant cell tumours of bone) and a single example of aneurysmal bone cyst. We found that osteoclasts are antigenically effete, failing to express granulocyte-monocyte, common leucocyte or other haemopoietic determinants; the only monocyte antigens detected on osteoclasts are My-7 and two closely related specificities, MCS.2 and DüHL60.4, which are also expressed by tissues outside the haemopoietic system. Our findings, taken together with recent transplantation studies, cast further doubt on the view that osteoclasts are specialized bone-resorbing macrophage-derived giant cells, and support a hypothesis that they are the end product of fusion of a hitherto unidentified circulating mononuclear cell type, the preosteoclast, which constitutes a cell lineage separate from those originating from the conventional multipotential haemopoietic stem cell, although still of bone marrow origin.

Origin of osteoclasts: mature monocytes and macrophages are capable of differentiating into osteoclasts under a suitable microenvironment prepared by bone marrow-derived stromal cells.

“…After a limited number of mouse alveolar macrophages (8- (15,16), the absence of calcitonin receptors and responsiveness in macrophages (17,18), and differences in membrane phenotypic expression between macrophages and osteoclasts (19,20).…”

Human cord blood monocytes undergo terminal osteoclast differentiation in vitro in the presence of culture medium conditioned by giant cell tumor of bone

“…Most of these cells had a fibroblastic morphology; rounded mononuclear cells and some multinucleated giant cells were also present. However, many of these multinucleated cells were macrophage polykaryons judged by their strong expression of HLA-DR and CDllc (Horton et al, 1984;Athanasou et al, 1992) as well as their low or undetectable levels of VNR and TRAP; such cells were not observed in the original tissue. After 15 days of culture, large numbers of these outgrown cells were present, and were confluent on the surface of the plastic within 21 days of culture.…”

Effects of Bisphosphonate Derivatives on Macrophage Function

“…Not only have they been found to have a protective action on the mineral component of bone, but have also been seen to inhibit osteoclast function [2,3]. The origin of osteoclasts from hematopoietic precursors is still controversial, yet it has been reported that they belong to the mononuclear phagocytic cell line [4,5], These compounds have been described as inhibitors of multinucleated cell precursors in the bone marrow culture system [6] [14], these biological parameters were considered in the evaluation of the effects of BPs on the MO. The effects of these drugs on phagocytosis was studied in two in vitro mod els which differed in their mechanism of in gestion.…”