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Osteoblastic stromal cells are capable of supporting osteoclast formation from hematopoietic precursors in the presence of osteotropic factors such as 1alpha,25(OH)(2)D(3), PTH, and IL-11. Osteoblastic stromal cells produce receptor activator of NF-kappaB ligand (RANKL), a type II membrane protein of the TNF ligand family, in response to these agents. Activated T lymphocytes also produce RANKL; however, the ability of this cell type to support osteoclast formation in vitro is unknown. Human PBMC-derived T cells, extracted using alphaCD3-coated magnetic beads, were cocultured with adherent murine spleen cells in the presence of Con A and a panel of cytokines. In the presence of Con A, bona fide osteoclasts were formed in vitro with activated T cells: IL-1alpha and TGFbeta further enhanced osteoclast numbers. PBMC-derived lymphocytes showed an increase in the mRNA expression of RANKL within 24 h of treatment with the same agents that were used to induce osteoclast formation. In synovial tissue sections with lymphoid infiltrates from RA patients, the expression of RANKL was demonstrated in CD3(+) T cells. The ability of activated T lymphocytes to support osteoclast formation may provide a mechanism for the potentiation of osteoclast formation and bone resorption in disease states such as rheumatoid arthritis.

Original publication

DOI

10.1006/bbrc.1999.1623

Type

Journal article

Journal

Biochem Biophys Res Commun

Publication Date

11/1999

Volume

265

Pages

144 - 150

Keywords

Aged, Animals, Animals, Newborn, Arthritis, Rheumatoid, Carrier Proteins, Cell Differentiation, Coculture Techniques, Concanavalin A, Female, Gene Expression Regulation, Hematopoietic Stem Cells, Humans, Interleukin-2, Lymphocyte Activation, Male, Membrane Glycoproteins, Mice, Mice, Inbred C57BL, Middle Aged, Osteoclasts, RANK Ligand, RNA, Messenger, Receptor Activator of Nuclear Factor-kappa B, Stromal Cells, Synovial Membrane, T-Lymphocytes, Transcription, Genetic, Transforming Growth Factor beta