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Research Service and Geriatric Research, Education, and Clinical Center, Veterans Administration Medical Center, and University of Texas Health Science Center San Antonio, Texas 78284
the Johns Hopkins Oncology Center (C.C.) Baltimore, Maryland 21209
Address all correspondence and requests for reprints to: G. David Roodman, M.D., Ph.D., Research Service (151) Veterans Administration Medical Center, 7400 Merton Minter Boulevard, San Antonio, Texas 78284.
Abstract
Nonadherent marrow mononuclear cells enriched for hematopoietic progenitor cells were cultured in semisolid medium with recombinant human granulocyte-macrophage colony-stimulating factor for 9 days to form colony forming unitgranulocyte macrophage (CFU-GM) colonies. 1,25-Dihydroxyvitamin D was then gently layered over the cultures. After 2 weeks, approximately 30% of the colonies that formed were composed of cells with a unique polygonal morphology. One hundred percent of the polygonal cells in these colonies crossreacted with the monoclonal antibody 23c6, which preferentially recognizes osteoclasts. Homogenous populations of these polygonal cells formed multinucleated cells (MNC) in suspension culture, 100% of which cross-reacted with the 23c6 monoclonal antibody, and greater than 90% of the MNC contracted in response to calcitonin. Approximately 20% of these MNC formed resorption lacunae on calcified matrices. These results suggest that 1) early osteoclast precursors are derived from CFUGM, the committed granulocyte-macrophage progenitor; 2) committed mononuclear osteoclast precursors have a distinct polygonal morphology and cross-react with monoclonal antibodies that recognize mature osteoclasts; and 3) these mononuclear precursors are capable of forming multinucleated cells which fulfill the functional criteria for osteoclasts. (Endocrinology 126: 2733–2741, 1990)
Footnotes
* This work was supported by Research Funds from the V.A., Grant AM-35188 from the NIDDK, and Grant CA-40035 from the NCI.
Recipient of a Clinical Investigator Award from the V.A. Research Service.
Received October 30, 1989.
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