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Chronic T cell activation is a hallmark of RA, and agents that target the CD28 receptor on T cells, which is required for T cell activation, are being increasingly used as therapies for RA and other inflammatory diseases. Lymphocytes play complex roles in the regulation of the skeleton, and although activated T cells and B cells secrete cytokines that promote skeletal decline, under physiologic conditions lymphocytes also have key protective roles in the stabilization of skeletal mass. Consequently, disruption of T cell costimulation may have unforeseen consequences for physiologic bone turnover. This study was undertaken to investigate the impact of pharmacologic CD28 T cell costimulation blockade on physiologic bone turnover and structure.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>C57BL6 mice were treated with CTLA\u20104Ig, a pharmacologic CD28 antagonist or with irrelevant control antibody (Ig), and serum biochemical markers of bone turnover were quantified by enzyme\u2010linked immunosorbent assay. Bone mineral density and indices of bone structure were further measured by dual x\u2010ray absorptiometry and micro\u2013computed tomography, respectively, and static and dynamic indices of bone formation were quantified using bone histomorphometry.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Pharmacologic disruption of CD28 T cell costimulation in mice significantly increased bone mass and enhanced indices of bone structure, a consequence of enhanced bone formation, concurrent with enhanced secretion of the bone anabolic factor Wnt\u201010b by T cells.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Inhibition of CD28 costimulation by CTLA\u20104Ig promotes T cell Wnt\u201010b production and bone formation and may represent a novel anabolic strategy for increasing bone mass in osteoporotic conditions.<\/jats:p><\/jats:sec>","DOI":"10.1002\/art.38319","type":"journal-article","created":{"date-parts":[[2014,1,27]],"date-time":"2014-01-27T14:14:41Z","timestamp":1390832081000},"page":"990-999","source":"Crossref","is-referenced-by-count":47,"title":["CTLA\u20104Ig\u2013Induced T Cell Anergy Promotes Wnt\u201010b Production and Bone Formation in a Mouse Model"],"prefix":"10.1002","volume":"66","author":[{"given":"Susanne","family":"Roser\u2010Page","sequence":"first","affiliation":[{"name":"Atlanta VAMC Decatur Georgia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tatyana","family":"Vikulina","sequence":"additional","affiliation":[{"name":"Emory University School of Medicine Atlanta Georgia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Majd","family":"Zayzafoon","sequence":"additional","affiliation":[{"name":"University of Alabama at Birmingham"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M. 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