title: Intermittent PTH(1-84) is osteoanabolic but not osteoangiogenic and relocates bone marrow blood vessels closer to bone-forming sites.
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.
authors.affiliation: Department of Kinesiology, The University of Texas at Arlington, Arlington, Texas 76019, USA. prisby@uta.edu
authors.forename: Rhonda
authors.initials: R
authors.lastname: Prisby
authors.forename: Alain
authors.initials: A
authors.lastname: Guignandon
authors.forename: Arnaud
authors.initials: A
authors.lastname: Vanden-Bossche
authors.forename: Fabrice
authors.initials: F
authors.lastname: Mac-Way
authors.forename: Marie-Thérèse
authors.initials: MT
authors.lastname: Linossier
authors.forename: Mireille
authors.initials: M
authors.lastname: Thomas
authors.forename: Norbert
authors.initials: N
authors.lastname: Laroche
authors.forename: Luc
authors.initials: L
authors.lastname: Malaval
authors.forename: Max
authors.initials: M
authors.lastname: Langer
authors.forename: Zoltz-Andrei
authors.initials: ZA
authors.lastname: Peter
authors.forename: Françoise
authors.initials: F
authors.lastname: Peyrin
authors.forename: Laurence
authors.initials: L
authors.lastname: Vico
authors.forename: Marie-Hélène
authors.initials: MH
authors.lastname: Lafage-Proust
mesh_terms: D045930:Anabolic Agents / Q000494:pharmacology*; D000818:Animals; D000906:Antibodies / Q000008:administration & dosage / Q000494:pharmacology; D001808:Blood Vessels / Q000187:drug effects*; D001853:Bone Marrow / Q000098:blood supply* / Q000187:drug effects; D016723:Bone Remodeling / Q000187:drug effects; D001842:Bone and Bones / Q000098:blood supply* / Q000000981:diagnostic imaging / Q000187:drug effects / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D008297:Male; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D009929:Organ Size / Q000187:drug effects; D010012:Osteogenesis / Q000187:drug effects*; D010281:Parathyroid Hormone / Q000008:administration & dosage / Q000494:pharmacology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011859:Radiography; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction / Q000187:drug effects; D013977:Tibia / Q000000981:diagnostic imaging / Q000187:drug effects / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000276:immunology
chemical_list: D045930:Anabolic Agents; D000906:Antibodies; D010281:Parathyroid Hormone; D012333:RNA, Messenger; D042461:Vascular Endothelial Growth Factor A