Regulatory T cells are expanded by Teriparatide treatment in humans and mediate intermittent PTH‐induced bone anabolism in mice |
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| Authors: | Mingcan Yu Patrizia D'Amelio Abdul Malik Tyagi Chiara Vaccaro Jau‐Yi Li Emory Hsu Ilaria Buondonno Francesca Sassi Jonathan Adams M Neale Weitzmann Richard DiPaolo Roberto Pacifici |
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| Institution: | 1. Division of Endocrinology, Metabolism and Lipids, Department of Medicine, Emory University, Atlanta, GA, USA;2. Gerontology Section, Department of Medical Sciences, University of Torino, Torino, Italy;3. Atlanta Department of Veterans Affairs Medical Center, Decatur, GA, USA;4. Department of Molecular Microbiology & Immunology, Saint Louis University School of Medicine, St. Louis, MO, USA;5. Immunology and Molecular Pathogenesis Program, Emory University, Atlanta, GA, USA |
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| Abstract: | Teriparatide is a bone anabolic treatment for osteoporosis, modeled in animals by intermittent PTH (iPTH) administration, but the cellular and molecular mechanisms of action of iPTH are largely unknown. Here, we show that Teriparatide and iPTH cause a ~two‐threefold increase in the number of regulatory T cells (Tregs) in humans and mice. Attesting in vivo relevance, blockade of the Treg increase in mice prevents the increase in bone formation and trabecular bone volume and structure induced by iPTH. Therefore, increasing the number of Tregs is a pivotal mechanism by which iPTH exerts its bone anabolic activity. Increasing Tregs pharmacologically may represent a novel bone anabolic therapy, while iPTH‐induced Treg increase may find applications in inflammatory conditions and transplant medicine. |
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| Keywords: | bone bone formation parathyroid hormone regulatory T cells |
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