| Literature DB >> 28162969 |
Yi Fan1, Jun-Ichi Hanai2, Phuong T Le3, Ruiye Bi4, David Maridas3, Victoria DeMambro3, Carolina A Figueroa3, Serkan Kir5, Xuedong Zhou6, Michael Mannstadt7, Roland Baron8, Roderick T Bronson9, Mark C Horowitz10, Joy Y Wu11, John P Bilezikian12, David W Dempster13, Clifford J Rosen14, Beate Lanske15.
Abstract
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.Entities:
Keywords: PTH; RANKL; bone resorption; lineage; receptor
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Year: 2017 PMID： 28162969 PMCID： PMC5342925 DOI： 10.1016/j.cmet.2017.01.001
Source DB: PubMed Journal: Cell Metab ISSN： 1550-4131 Impact factor: 27.287