Parathyroid Diseases and T Cells

• Type of Material: Article
• Authors: M Neale Weitzmann, Emory University; Roberto Pacifici, Emory University
• Language: English
• Date: 2017-06-01
• Publisher: Current Medicine Group
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2017, Springer Science+Business Media New York (outside the USA).
• Final Published Version (URL): http://dx.doi.org/10.1007/s11914-017-0359-y
• Title of Journal or Parent Work: Current Osteoporosis Reports
• ISSN: 1544-1873
• Volume: 15
• Issue: 3
• Start Page: 135
• End Page: 141
• Grant/Funding Information: Roberto Pacifici is supported by NIH grants from NIDDK (DK108842), NIAMS (AR54625) and RR028009.; M. Neale Weitzmann is supported by a grant from the Biomedical Laboratory Research & Development Service of the VA Office of Research and Development (5I01BX000105) and by National Institutes of Health (NIH) grants from NIAMS (AR056090, AR059364, AR068157, and AR070091) and NIA AG040013.
• Keywords: RANK LIGAND; TNF-ALPHA; Endocrinology & Metabolism; Parathyroid hormone; PTH; Life Sciences & Biomedicine; OSTEOPROTEGERIN LIGAND; ANABOLIC ACTIVITY; Osteoimmunology; OSTEOBLASTIC CELLS; INCREASED BONE-RESORPTION; NECROSIS-FACTOR-ALPHA; Osteoporosis; Science & Technology; HORMONE; IN-VIVO; ESTROGEN DEFICIENCY; Tcells; Hyperparathyroidism
• Research Categories: Health Sciences, Oncology; Health Sciences, Immunology; Health Sciences, Medicine and Surgery

Abstract

Purpose of Review: This review summarizes studies into the permissive role of T cells in the bone catabolic effects of hyperparathyroidism and parathyroid hormone (PTH). Recent Findings: Work in animals combined with recent translational studies in humans now highlight the potent amplificatory action of T cells on PTH-induced bone resorption. Mechanistic animal studies reveal a complex pathway by which PTH exploits natural self-renewal functions of CD4+T cells, to drive TNFα production that promotes formation of IL-17A secreting Th17 T cells. TNFα and IL-17 further amplify osteoblastic receptor activator of NF-κB ligand (RANKL) production and down-modulate osteoprotegerin (OPG), establishing conditions propitious for osteoclastic bone resorption. Summary: These findings are consistent with, and add to, the traditional view of PTH-induced bone loss involving only osteoblast-lineage cells. T cells potently amplify traditional pathways and provide permissive costimulatory signals to bone marrow stromal cells, facilitating the development of an increased RANKL/OPG ratio favourable to bone resorption and bone loss.