Intermittent PTH(1–84) is osteoanabolic but not osteoangiogenic and relocates bone marrow blood vessels closer to bone‐forming sites |
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Authors: | Rhonda Prisby Alain Guignandon Arnaud Vanden‐Bossche Fabrice Mac‐Way Marie‐Thérèse Linossier Mireille Thomas Norbert Laroche Luc Malaval Max Langer Zoltz‐Andrei Peter Françoise Peyrin Laurence Vico Marie‐Hélène Lafage‐Proust |
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Institution: | 1. Department of Kinesiology, The University of Texas at Arlington, Arlington, Texas, USA;2. Faculté de Médecine, Université de Lyon, Saint‐Etienne, France;3. INSERM U890, Université J Monnet, Saint‐Etienne, France;4. Division of Nephrology, CHUQ, L'H?tel Dieu de Québec, Laval University, Quebec, Canada;5. INSERM U630, CNRS, UMR5220, Université Lyon 1, INSA‐Lyon, CREATIS, Lyon, France, and European Synchrotron Radiation Facility, Grenoble, France;6. Université Paris 10–Ouest Nanterre La Défense, PST/IUT de Ville d'Avray, Département GTE, Ville d'Avray, France |
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Abstract: | Intermittent parathyroid hormone (PTH) is anabolic for bone. Our aims were to determine (1) whether PTH stimulates bone angiogenesis and (2) whether vascular endothelial growth factor (VEGF A) mediates PTH‐induced bone accrual. Male Wistar rats were given PTH(1–84) daily, and trabecular bone mass increased 150% and 92% after 30 and 15 days, respectively. The vascular system was contrasted to image and quantify bone vessels with synchrotron radiation microtomography and histology. Surprisingly, bone vessel number was reduced by approximately 25% and approximately 40% on days 30 and 15, respectively. PTH redistributed the smaller vessels closer to bone‐formation sites. VEGF A mRNA expression in bone was increased 2 and 6 hours after a single dose of PTH and returned to baseline by 24 hours. Moreover, anti‐VEGF antibody administration (1) blunted the PTH‐induced increase in bone mass and remodeling parameters, (2) prevented the relocation of bone vessels closer to bone‐forming sites, and (3) inhibited the PTH‐induced increase in mRNA of neuropilin 1 and 2, two VEGF coreceptors associated with vascular development and function. In conclusion, PTH(1–84) is osteoanabolic through VEGF‐related mechanism(s). Further, PTH spatially relocates blood vessels closer to sites of new bone formation, which may provide a microenvironment favorable for growth. © 2011 American Society for Bone and Mineral Research |
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Keywords: | bone vessel quantitative imaging Angiogenesis Rat Parathyroid hormone Neuropilin |
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