Functions of vasopressin and oxytocin in bone mass regulation

Li Sun, Roberto Tamma, Tony Yuen, Graziana Colaianni, Yaoting Ji, Concetta Cuscito, Jack Bailey, Samarth Dhawan, Ping Lu, Cosima D. Calvano, Ling Ling Zhu, Carlo G. Zambonin, Adriana Di Benedetto, Agnes Stachnik, Peng Liu, Maria Grano, Silvia Colucci, Terry F. Davies, Maria I. New, Alberta ZalloneMone Zaidi

Research output: Contribution to journalArticlepeer-review

36 Scopus citations

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-/- doublemutant mice. However, although Oxtr is not indispensable for Avp action in inhibiting osteoblastogenesis and gene expression, Avpstimulated 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.

Original languageEnglish
Pages (from-to)164-169
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume113
Issue number1
DOIs
StatePublished - 5 Jan 2016

Keywords

  • Osteoblast
  • Osteoporosis
  • Skeleton

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