engleski

Depletion of CD4 and CD8 lymphocytes in mice in vivo enhances 1, 25-dihydroxyvitamin D3-stimulated osteoclast-like cell formation in vitro by a mechanism that is dependent on prostaglandin synthesis

To investigate the role of T lymphocytes in osteoclastogenesis, we performed in vivo depletion of CD4 and/or CD8 subsets of T lymphocytes and evaluated in vitro osteoclast-like cell (OCL) formation. T-lymphocyte depletion (TLD) with monoclonal antibodies was confirmed 24 hours later by flow cytometry. OCL formation was stimulated with 1, 25(OH)2D3 in bone marrow (BM) and with rmRANK-L and rmM-CSF in spleen cell cultures. OCL formation was 2-fold greater in stimulated BM cultures from TLD mice than in those from intact mice. In contrast, TLD did not alter OCL formation in spleen cell cultures, which contain significantly fewer stromal cells than BM. The effects of TLD seemed mediated by enhanced PG synthesis since PGE2 concentration in the medium of stimulated BM cultures from TLD mice was 5-fold higher than in BM cultures from intact mice, and indomethacin treatment abolished the stimulatory effect of TLD on OCL formation. There was a 2-fold increase of RANK-L expression and an almost complete suppression of OPG expression in stimulated BM cultures from TLD mice compared to those from intact mice. Although there was a small (20%) increase in IL-1alpha expression in BM cultures from TLD mice, TLD in mice lacking active type I IL-1 receptor produced similar effect on OCL formation as in wild type mice. Our data demonstrate that TLD upregulates OCL formation in vitro by increasing PG production, which, in turn, produces reciprocal changes in RANK-L and OPG expression. These results suggest that T lymphocytes influence osteoclastogenesis by altering BM stromal cell function.

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