Regulatory T cells are expanded by Teriparatide treatment in humans and mediate intermittent PTH‐induced bone anabolism in mice

• Published in: EMBO reports 2018-01, Vol.19 (1), p.156-171
• Main Authors: Yu, Mingcan, D'Amelio, Patrizia, Tyagi, Abdul Malik, Vaccaro, Chiara, Li, Jau‐Yi, Hsu, Emory, Buondonno, Ilaria, Sassi, Francesca, Adams, Jonathan, Weitzmann, M Neale, DiPaolo, Richard, Pacifici, Roberto
• Format: Article
• Language: English
• Subjects: Aged; Animals; Biocompatibility; Biomarkers - metabolism; Biomedical materials; bone; Bone Density Conservation Agents - therapeutic use; bone formation; Bone growth; Calcium - therapeutic use; Calcium-Regulating Hormones and Agents - therapeutic use; Cancellous bone; Collagen Type I - genetics; Collagen Type I - metabolism; Core Binding Factor Alpha 1 Subunit - genetics; Core Binding Factor Alpha 1 Subunit - metabolism; Disease Models, Animal; EMBO19; EMBO24; Female; Gene Expression; Humans; Immunoregulation; Inflammation; Integrin-Binding Sialoprotein - genetics; Integrin-Binding Sialoprotein - metabolism; Lymphocyte Count; Lymphocytes; Lymphocytes T; Mice; Molecular modelling; Osteocalcin - genetics; Osteocalcin - metabolism; Osteogenesis; Osteoporosis; Osteoporosis, Postmenopausal - drug therapy; Osteoporosis, Postmenopausal - genetics; Osteoporosis, Postmenopausal - metabolism; Osteoporosis, Postmenopausal - pathology; Ovariectomy; Parathyroid; Parathyroid hormone; Pharmacology; regulatory T cells; Rodents; Sp7 Transcription Factor - genetics; Sp7 Transcription Factor - metabolism; T-Lymphocytes, Regulatory - cytology; T-Lymphocytes, Regulatory - drug effects; T-Lymphocytes, Regulatory - metabolism; Teriparatide - therapeutic use; Transforming Growth Factor beta - genetics; Transforming Growth Factor beta - metabolism; Treatment Outcome; Vitamin D - analogs & derivatives; Vitamin D - therapeutic use
• ISSN: 1469-221X; 1469-3178
• DOI: 10.15252/embr.201744421

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. Synopsis Parathyroid hormone (PTH) causes a ~two–threefold increase in the number of regulatory T cells (Tregs) in humans and mice, an effect which is required for PTH to exert its bone anabolic activity. Parathyroid hormone (PTH) increases the number of regulatory T cells (Tregs) in humans and mice. Blockade of the PTH‐induced increase in Tregs prevents iPTH‐induced bone anabolism. Graphical Abstract Parathyroid hormone (PTH) causes a ~two–threefold increase in the number of regulatory T cells (Tregs) in humans and mice, an effect which is required for PTH to exert its bone anabolic activity.