Regulation of bone remodeling by vasopressin explains the bone loss in hyponatremia

Roberto Tamma, Li Sun, Concetta Cuscito, Ping Lu, Michelangelo Corcelli, Jianhua Li, Graziana Colaianni, Surinder S. Moonga, Adriana Di Benedetto, Maria Grano, Silvia Colucci, Tony Yuen, Maria I. New, Alberta Zallone, Mone Zaidi

Research output: Contribution to journalArticlepeer-review

100 Scopus citations

Abstract

Although hyponatremia is known to be associated with osteoporosis and a high fracture risk, the mechanism through which bone loss ensues has remained unclear. As hyponatremic patients have elevated circulating arginine-vasopressin (AVP) levels, we examined whether AVP can affect the skeleton directly as yet another component of the pituitary-bone axis. Here, we report that the two Avp receptors, Avpr1α and Avpr2, coupled to Erk activation, are expressed in osteoblasts and osteoclasts. AVP injected into wild-type mice enhanced and reduced, respectively, the formation of bone-resorbing osteoclasts and bone-forming osteoblasts. Conversely, the exposure of osteoblast precursors to Avpr1α or Avpr2 antagonists, namely SR49059 or ADAM, increased osteoblastogenesis, as did the genetic deletion of Avpr1α. In contrast, osteoclast formation and bone resorption were both reduced in Avpr1α-/- cultures. This process increased bone formation and reduced resorption resulted in a profound enhancement of bone mass in Avpr1α-/- mice and in wild-type mice injected with SR49059. Collectively, the data not only establish a primary role for Avp signaling in bone mass regulation, but also call for further studies on the skeletal actions of Avpr inhibitors used commonly in hyponatremic patients.

Original languageEnglish
Pages (from-to)18644-18649
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume110
Issue number46
DOIs
StatePublished - 12 Nov 2013

Keywords

  • Osteopenia
  • Oxytocin
  • Pituitary hormone

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