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T cell‐mediated increased osteoclast formation from peripheral blood as a mechanism for crohn's disease‐associated bone loss
Author(s) -
Oostlander Angela E.,
Everts Vincent,
Schoenmaker Ton,
Bravenboer Nathalie,
van Vliet Sandra J.,
van Bodegraven Ad A.,
Lips Paul,
de Vries Teun J.
Publication year - 2012
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.23352
Subject(s) - osteoclast , peripheral blood mononuclear cell , rankl , immunology , cytokine , chemistry , in vitro , cell , biology , microbiology and biotechnology , medicine , biochemistry , receptor , activator (genetics)
The pathophysiology of osteoporosis in patients with Crohn's disease (CD) is still not completely elucidated. In this study, we evaluated osteoclastogenesis from peripheral blood cells of CD patients and studied the role of lymphocytes and inflammatory cytokines in this process. Peripheral blood mononuclear cells from seven patients with quiescent CD and matched healthy controls were isolated, and separated into T cells, B cells, and a T‐ and B‐cell depleted fraction. In various culture combinations, osteoclast formation in the absence of the osteoclastogenic factors RANKL and M‐CSF was assessed by scoring the number of tartrate‐resistant acid phosphatase (TRACP) positive multinucleated cells (MNCs). Cytokine levels in culture supernatants were measured. Formation of heterogeneous cell clusters in culture was noticed; a process that was inhibited by anti‐LFA‐1. In CD cultures, mean cluster area was up to threefold higher than in control cultures, and shown to be induced by T cells. Over tenfold higher numbers of TRACP + MNCs were found in CD cultures, but exclusively in cultures containing T cells. Formation of cell clusters correlated strongly with formation of TRACP + MNCs. Both cell cluster formation and osteoclast formation were related to IL‐17 levels in vitro. In conclusion, osteoclastogenesis, preceded by cell cluster formation, is T cell‐mediated and increased in patients with quiescent CD. Our findings suggest heterotypic interactions between osteoclast precursors and T cells to be a triggering step in osteoclast formation in CD. Furthermore, our results propose a possible role for IL‐17 in osteoclastogenesis in CD patients, and as such in CD‐associated bone loss. J. Cell. Biochem. 113: 260–268, 2012. © 2011 Wiley Periodicals, Inc.