The multinucleated osteoclast is the primary bone resorbing cell. Although much has been learned about bone resorption and calcium homeostasis, little is known about the cell biology of osteoclasts because of their relative inaccessability and fragility. Because of the abundant evidence that osteoclasts arise from cells of monocyte-macrophage lineage in the marrow, we have recently developed a long-term marrow system for studying the formation of osteoclast-like cells in human and baboon marrow. The marrow culture system utilizes the recently developed technique of long-term marrow culture, which provides an appropriate environment for normal marrow cell growth and maturation. These cultures are dependent on the formation of an adherent cell layer which duplicates the normal marrow microenvironment. We have found that 1,25 dihydroxycholecalciferol, an important differentiating agent for osteoclasts, stimulates the formation of multinucleated cells in these cultures. The multinucleated cells which formed have the functional and morphologic characteristics as well as the enzymatic profiles of osteoclasts. In this proposal we will use these marrow culture systems to: 1) compare the biologic and physical properties of these marrow multinucleated cells to authentic osteoclasts; 2) compare the growth characteristics of marrow-derived osteoclast-like cells in long-term cultures from fetal, neonatal, pubescent and adult baboon marrow; 3) compare the characteristics of human and baboon osteoclast-like cells formed in vitro; 4) enrich cell populations for the precursors of these osteoclast-like cells. As part of this goal we will initiate studies to prepare monoclonal antibody to human osteoclast-like cells; and 5) to identify and characterize the mononuclear precursor of these osteoclast-like cells.
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