M Neale Weitzmann1,2,3, Roberto Pacifici4,5. 1. Atlanta U.S. Department of Veterans Affairs Medical Center, Decatur, GA, 30033, USA. mweitzm@emory.edu. 2. Division of Endocrinology and Metabolism and Lipids, Department of Medicine, Emory University School of Medicine, 101 Woodruff Circle, 1305 WMB, Atlanta, GA, 30322, USA. mweitzm@emory.edu. 3. Emory Winship Cancer Institute, Emory University, Atlanta, GA, 30322, USA. mweitzm@emory.edu. 4. Division of Endocrinology and Metabolism and Lipids, Department of Medicine, Emory University School of Medicine, 101 Woodruff Circle, 1305 WMB, Atlanta, GA, 30322, USA. 5. Immunology and Molecular Pathogenesis Program, Emory University, Atlanta, GA, 30322, USA.
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. 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.
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. 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.
Entities:
Keywords:
Hyperparathyroidism; Osteoimmunology; Osteoporosis; PTH; Parathyroid hormone; T cells
Authors: S Kotake; N Udagawa; N Takahashi; K Matsuzaki; K Itoh; S Ishiyama; S Saito; K Inoue; N Kamatani; M T Gillespie; T J Martin; T Suda Journal: J Clin Invest Date: 1999-05 Impact factor: 14.808
Authors: Jerid W Robinson; Jau-Yi Li; Lindsey D Walker; Abdul Malik Tyagi; Michael A Reott; Mingcan Yu; Jonathan Adams; M Neale Weitzmann; Roberto Pacifici Journal: J Bone Miner Res Date: 2015-04 Impact factor: 6.741
Authors: T J Yun; P M Chaudhary; G L Shu; J K Frazer; M K Ewings; S M Schwartz; V Pascual; L E Hood; E A Clark Journal: J Immunol Date: 1998-12-01 Impact factor: 5.422
Authors: Abdullah N Ben-awadh; Jesus Delgado-Calle; Xiaolin Tu; Kali Kuhlenschmidt; Matthew R Allen; Lilian I Plotkin; Teresita Bellido Journal: Endocrinology Date: 2014-05-30 Impact factor: 4.736
Authors: Rosilene Motta Elias; Maria Aparecida Dalboni; Ana Carolina E Coelho; Rosa M A Moysés Journal: Curr Osteoporos Rep Date: 2018-12 Impact factor: 5.096
Authors: E Dozio; E Passeri; E Vianello; S Palmieri; C Eller-Vainicher; M Corsi Romanelli; S Corbetta Journal: Mediators Inflamm Date: 2020-01-17 Impact factor: 4.711