Intermittent PTH(1–84) is osteoanabolic but not osteoangiogenic and relocates bone marrow blood vessels closer to bone-forming sites

Authors

  • Rhonda Prisby,

    Corresponding author
    1. Department of Kinesiology, The University of Texas at Arlington, Arlington, Texas, USA
    • Department of Kinesiology, The University of Texas Arlington, 500 West Nedderman Drive, MAC 147, Arlington, TX 76019, USA.
    Search for more papers by this author
  • Alain Guignandon,

    1. Faculté de Médecine, Université de Lyon, Saint-Etienne, France
    2. INSERM U890, Université J Monnet, Saint-Etienne, France
    Search for more papers by this author
  • Arnaud Vanden-Bossche,

    1. Faculté de Médecine, Université de Lyon, Saint-Etienne, France
    2. INSERM U890, Université J Monnet, Saint-Etienne, France
    Search for more papers by this author
  • Fabrice Mac-Way,

    1. Faculté de Médecine, Université de Lyon, Saint-Etienne, France
    2. INSERM U890, Université J Monnet, Saint-Etienne, France
    3. Division of Nephrology, CHUQ, L'Hôtel Dieu de Québec, Laval University, Quebec, Canada
    Search for more papers by this author
  • Marie-Thérèse Linossier,

    1. Faculté de Médecine, Université de Lyon, Saint-Etienne, France
    2. INSERM U890, Université J Monnet, Saint-Etienne, France
    Search for more papers by this author
  • Mireille Thomas,

    1. Faculté de Médecine, Université de Lyon, Saint-Etienne, France
    2. INSERM U890, Université J Monnet, Saint-Etienne, France
    Search for more papers by this author
  • Norbert Laroche,

    1. Faculté de Médecine, Université de Lyon, Saint-Etienne, France
    2. INSERM U890, Université J Monnet, Saint-Etienne, France
    Search for more papers by this author
  • Luc Malaval,

    1. Faculté de Médecine, Université de Lyon, Saint-Etienne, France
    2. INSERM U890, Université J Monnet, Saint-Etienne, France
    Search for more papers by this author
  • Max Langer,

    1. Faculté de Médecine, Université de Lyon, Saint-Etienne, France
    2. INSERM U630, CNRS, UMR5220, Université Lyon 1, INSA-Lyon, CREATIS, Lyon, France, and European Synchrotron Radiation Facility, Grenoble, France
    Search for more papers by this author
  • Zoltz-Andrei Peter,

    1. Université Paris 10–Ouest Nanterre La Défense, PST/IUT de Ville d'Avray, Département GTE, Ville d'Avray, France
    Search for more papers by this author
  • Françoise Peyrin,

    1. Faculté de Médecine, Université de Lyon, Saint-Etienne, France
    2. INSERM U630, CNRS, UMR5220, Université Lyon 1, INSA-Lyon, CREATIS, Lyon, France, and European Synchrotron Radiation Facility, Grenoble, France
    Search for more papers by this author
  • Laurence Vico,

    1. Faculté de Médecine, Université de Lyon, Saint-Etienne, France
    2. INSERM U890, Université J Monnet, Saint-Etienne, France
    Search for more papers by this author
  • Marie-Hélène Lafage-Proust

    1. Faculté de Médecine, Université de Lyon, Saint-Etienne, France
    2. INSERM U890, Université J Monnet, Saint-Etienne, France
    Search for more papers by this author

  • For a Commentary on this article, please see Towler (J Bone Miner Res. 2011;26:2579–2582. DOI: 10.1002/jbmr.523).

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

Ancillary