{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T15:07:39Z","timestamp":1779203259728,"version":"3.51.4"},"reference-count":53,"publisher":"American Society for Clinical Investigation","issue":"13","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2016,8,18]]},"abstract":"<jats:p>\n                    A number of studies in model animal systems and in the clinic have established that RANKL promotes bone resorption. Paradoxically, we found that pulsing ovariectomized mice with low-dose RANKL suppressed bone resorption, decreased the levels of proinflammatory effector T cells and led to increased bone mass. This effect of RANKL is mediated through the induction of FoxP3\n                    <jats:sup>+<\/jats:sup>\n                    CD25\n                    <jats:sup>+<\/jats:sup>\n                    regulatory CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cells (Tc\n                    <jats:sub>REG<\/jats:sub>\n                    ) by osteoclasts. Here, we show that pulses of low-dose RANKL are needed to induce Tc\n                    <jats:sub>REG<\/jats:sub>\n                    , as continuous infusion of identical doses of RANKL by pump did not induce Tc\n                    <jats:sub>REG<\/jats:sub>\n                    . We also show that low-dose RANKL can induce Tc\n                    <jats:sub>REG<\/jats:sub>\n                    at 2, 3, 6, and 10 weeks after ovariectomy. Our results show that low-dose RANKL treatment in ovariectomized mice is optimal at once-per-month doses to maintain the bone mass. Finally, we found that treatment of ovariectomized mice with the Cathepsin K inhibitor odanacatib also blocked Tc\n                    <jats:sub>REG<\/jats:sub>\n                    induction by low-dose RANKL. We interpret this result to indicate that antigens presented to CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cells by osteoclasts are derived from the bone protein matrix because Cathepsin K degrades collagen in the bone. Taken together, our studies provide a basis for using low-dose RANKL as a potential therapeutic for postmenopausal osteoporosis.\n                  <\/jats:p>","DOI":"10.1172\/jci.insight.88839","type":"journal-article","created":{"date-parts":[[2016,8,17]],"date-time":"2016-08-17T11:01:00Z","timestamp":1471431660000},"source":"Crossref","is-referenced-by-count":10,"title":["Pulsed low-dose RANKL as a potential therapeutic for postmenopausal osteoporosis"],"prefix":"10.1172","volume":"1","author":[{"given":"Anna","family":"Cline-Smith","sequence":"first","affiliation":[{"name":"Department of Molecular Microbiology and Immunology, St. Louis University School of Medicine, St. Louis, Missouri, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jesse","family":"Gibbs","sequence":"additional","affiliation":[{"name":"Division of Bone and Mineral Diseases, Department of Medicine, Washington University in St. Louis, St. Louis, Missouri, 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