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Proc Natl Acad Sci U S A. 2016 Jan 5;113(1):164-9. doi: 10.1073/pnas.1523762113. Epub 2015 Dec 22.

Functions of vasopressin and oxytocin in bone mass regulation.

Author information

1
The Mount Sinai Bone Program, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY 10029;
2
Department of Basic Medical Science, Neurosciences and Sensory Organs, University of Bari, 70124 Bari, Italy;
3
Department of Chemistry, University of Bari Aldo Moro, Bari 70124, Italy;
4
Department of Clinical and Experimental Medicine, University of Foggia, Foggia 71122, Italy.
5
The Mount Sinai Bone Program, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY 10029; maria.new@mssm.edu mone.zaidi@mssm.edu.

Abstract

Prior studies show that oxytocin (Oxt) and vasopressin (Avp) have opposing actions on the skeleton exerted through high-affinity G protein-coupled receptors. We explored whether Avp and Oxtr can share their receptors in the regulation of bone formation by osteoblasts. We show that the Avp receptor 1α (Avpr1α) and the Oxt receptor (Oxtr) have opposing effects on bone mass: Oxtr(-/-) mice have osteopenia, and Avpr1α(-/-) mice display a high bone mass phenotype. More notably, this high bone mass phenotype is reversed by the deletion of Oxtr in Oxtr(-/-):Avpr1α(-/-) double-mutant mice. However, although Oxtr is not indispensable for Avp action in inhibiting osteoblastogenesis and gene expression, Avp-stimulated gene expression is inhibited when the Oxtr is deleted in Avpr1α(-/-) cells. In contrast, Oxt does not interact with Avprs in vivo in a model of lactation-induced bone loss in which Oxt levels are high. Immunofluorescence microscopy of isolated nucleoplasts and Western blotting and MALDI-TOF of nuclear extracts show that Avp triggers Avpr1α localization to the nucleus. Finally, a specific Avpr2 inhibitor, tolvaptan, does not affect bone formation or bone mass, suggesting that Avpr2, which primarily functions in the kidney, does not have a significant role in bone remodeling.

KEYWORDS:

osteoblast; osteoporosis; skeleton

PMID:
26699482
PMCID:
PMC4711832
DOI:
10.1073/pnas.1523762113
[Indexed for MEDLINE]
Free PMC Article

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