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Characterization of Immortalized Osteoclast Precursors Developed from Mice Transgenic for Both bcl-X_L and Simian Virus 40 Large T Antigen¹

Department of Medicine, Division of Hematology (T.A.H., H.C., S.V.R., S.J.C., G.D.R.), University of Texas Health Science Center, San Antonio, Texas 78284; the National Institutes of Health (S.H.J.), Bethesda, Maryland 20892; the Department of Research, Veterans Administration Medical Center (J.L.), Newington, Connecticut 06111; and the Audie Murphy Veterans Administration Hospital (G.D.R.), San Antonio, Texas 78284

Address all correspondence and requests for reprints to: G. David Roodman, M.D., Ph.D., Research Service (151), Audie Murphy Veterans Administration Hospital, 7400 Merton Minter Boulevard, San Antonio, Texas 78284. E-mail: roodman{at}uthscsa.edu

We recently developed an immortalized osteoclast (OCL) precursor cell line that forms large numbers of OCLs. This cell line was derived from mice doubly transgenic for bcl-X_L and large T antigen that was targeted to cells in the OCL lineage (bcl-X_L/Tag cells). We have now characterized these cells in terms of their surface and enzymatic phenotype, responsiveness to osteotropic factors, and differentiation potential. The bcl-X_L/Tag cells expressed interleukin-1 receptors 1 and 2, gelatinase B (MMP9), as well as Mac-1, CD16/CD32 (Fc receptors), CD45.2 (common leukocyte marker), CD86 (costimulatory molecule expressed on B cells, follicular dendritic cells, and thymic epithelium), major histocompatibility complex I, and nonspecific esterase when cocultured with MC3T3E1 cells. However, they did not express the antigens for F4/80 (mature macrophage/dendritic cell marker) by immunostaining. Treatment of bcl-X_L/Tag cells, cocultured with MC3T3E1 cells, with the combination of 1,25-dihydroxyvitamin D₃ and dexamethasone induced high levels of OCL formation. The bcl-X_L/Tag cells formed large numbers of OCLs when cultured with RANK ligand and macrophage colony-stimulating factor in the absence of feeder cells. In the absence of RANK ligand and a feeder cell layer, 100% of the cells differentiated into F4/80-positive cells. However, neither PTH nor PTH-related protein enhanced OCL formation by bcl-X_L/Tag cells even when they were cocultured with primary osteoblasts, suggesting that they differ from primary mouse bone marrow cells in their responsiveness to PTH/PTH-related protein. Thus, bcl-X_L/Tag cells have many of the properties of primary mouse OCL precursors and should be very useful for studies of OCL differentiation and divergence of OCL precursors from the macrophage lineage.

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