The origin of osteoclasts:

Abstract

Recent evidence for an extraskeletal origin of osteoelasts and the historical record of the genesis of osteoelasts are examined critically. Reviews of the structure, function and development of osteoelasts from mononuclear precursors, the local regulation of bone resorption and the coupling of bone formation to preceding resorption are presented as a background for discussing the clinical implications for management of osteolytic bone diseases. The roles of osteoelasts and macrophages as phagocytes are compared and contrasted, and recent evidence for macrophage heterogeneity resulting from site-specific monoblastic precursors is reviewed. The implications of these recent developments in macrophage biology are extrapolated to osteoelasts and the existence of site-specific, extraskeletal tsteoclast precursors is proposed. Finally, the investigative challenges inherent in these perspectives are discussed.

Hypercalcemia induced with an arotinoid in thyroparathyroidectomized rats. New model to study bone resorption in vivo.

“…Osteoclasts are thought to originate from stem cells in the bone marrow under the influence of hemopoietic growth factors. Multinucleated osteoclasts are then generated by fusion of precursor cells (4,5). The activation of osteoclasts can be studied using the acute hypercalcemic effect of PTH in parathyroidectomized rats.…”

An Ultrastructural Study of Cell-Cell Contact between Mouse Spleen Cells and Calvaria-Derived Osteoblastic Cells in a Co-Culture System for Osteoclast Formation.

“…Multinucleated cells formed in this coculture system in response to bone-resorbing factors such as 1 a, 25-dihydoxyvitamin D3 [1 a, 25(OH)2D3], parathyroid hormone (PTH), prostaglandin E2 (PGE2) and interleukin 1 (IL-1) showed not only tartrate-resistant acid phosphatase (TRAP) activity and abundant calcitonin receptors [4,30], but also resorbed bone and dentine with typical ruffled borders [22]. The characteristics of these multinucleated cells generated in this co-culture system, therefore, satisfied the major criteria for authentic osteoclasts [1, 10,17,18]. Cell-cell contact between spleen cells and osteoblastic stromal cells is thought to be necessary for the osteoclast formation, since no TRAPpositive osteoclasts were formed when the two types of cells were co-cultured without direct contact even in the presence of bone-resorbing factors.…”

Osteoclast biology in the osteopetrotic (op) rat

“…Normal osteoclast differentiation and function depend on both stem-cell competence and local regulatory signals from the cells and matrix of the skeletal microenvironment (Marks, 1983). The ability to cure op rats by transplantation from normal littermates of bone marrow that contains competent stem cells Nisbet et al, 1983) infers that the primary defect in this mutation resides within the osteoclast or its progenitors .…”