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Parathyroid Hormone Directs Bone Marrow Mesenchymal Cell Fate.

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机构: [1]Division of Bone and Mineral Research, Harvard School of Dental Medicine, Boston, MA 02115, USA [2]State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan 610041, China [3]Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA 02215, USA [4]Maine Medical Center Research Institute, Scarborough, ME 04074, USA [5]Endocrine Unit, Massachusetts General Hospital and Department of Medicine, Harvard Medical School, Boston, MA 02114, USA [6]Department of Cancer Biology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02215, USA [7]Department of Microbiology and Immunobiology, Harvard Medical School, Boston, MA 02215, USA [8]Department of Orthopaedics and Rehabilitation, Yale School of Medicine, New Haven, CT 06510, USA [9]Division of Endocrinology, Stanford University School of Medicine, Stanford, CA 94305, USA [10]Department of Medicine, College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA [11]Department of Pathology, College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA
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Intermittent PTH administration builds bone mass and prevents fractures, but its mechanism of action is unclear. We genetically deleted the PTH/PTHrP receptor (PTH1R) in mesenchymal stem cells using Prx1Cre and found low bone formation, increased bone resorption, and high bone marrow adipose tissue (BMAT). Bone marrow adipocytes traced to Prx1 and expressed classic adipogenic markers and high receptor activator of nuclear factor kappa B ligand (Rankl) expression. RANKL levels were also elevated in bone marrow supernatant and serum, but undetectable in other adipose depots. By cell sorting, Pref1+RANKL+ marrow progenitors were twice as great in mutant versus control marrow. Intermittent PTH administration to control mice reduced BMAT significantly. A similar finding was noted in male osteoporotic patients. Thus, marrow adipocytes exhibit osteogenic and adipogenic characteristics, are uniquely responsive to PTH, and secrete RANKL. These studies reveal an important mechanism for PTH's therapeutic action through its ability to direct mesenchymal cell fate. Copyright © 2017 Elsevier Inc. All rights reserved.

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出版当年[2017]版:
大类 | 1 区 生物
小类 | 1 区 细胞生物学 1 区 内分泌学与代谢
最新[2023]版:
大类 | 1 区 生物学
小类 | 1 区 细胞生物学 1 区 内分泌学与代谢
第一作者:
第一作者机构: [1]Division of Bone and Mineral Research, Harvard School of Dental Medicine, Boston, MA 02115, USA [2]State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan 610041, China
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通讯机构: [1]Division of Bone and Mineral Research, Harvard School of Dental Medicine, Boston, MA 02115, USA [5]Endocrine Unit, Massachusetts General Hospital and Department of Medicine, Harvard Medical School, Boston, MA 02114, USA
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