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.

Autore Pugliese

• Grano Maria , Colucci Silvia Concetta

Tutti gli autori

• GRANO M.;COLUCCI S.C.

Titolo volume/Rivista

Non Disponibile

Anno di pubblicazione

2013

ISSN

0027-8424

ISBN

Non Disponibile

Numero di citazioni Wos

54

Ultimo Aggiornamento Citazioni

Non Disponibile

Numero di citazioni Scopus

58

Ultimo Aggiornamento Citazioni

Non Disponibile

Settori ERC

Non Disponibile

Codici ASJC

Non Disponibile