title: Regulation of bone remodeling by vasopressin explains the bone loss in hyponatremia.
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.
authors.affiliation: Department of Histology, University of Bari, 70124 Bari, Italy.
authors.forename: Roberto
authors.initials: R
authors.lastname: Tamma
authors.forename: Li
authors.initials: L
authors.lastname: Sun
authors.forename: Concetta
authors.initials: C
authors.lastname: Cuscito
authors.forename: Ping
authors.initials: P
authors.lastname: Lu
authors.forename: Michelangelo
authors.initials: M
authors.lastname: Corcelli
authors.forename: Jianhua
authors.initials: J
authors.lastname: Li
authors.forename: Graziana
authors.initials: G
authors.lastname: Colaianni
authors.forename: Surinder S
authors.initials: SS
authors.lastname: Moonga
authors.forename: Adriana
authors.initials: A
authors.lastname: Di Benedetto
authors.forename: Maria
authors.initials: M
authors.lastname: Grano
authors.forename: Silvia
authors.initials: S
authors.lastname: Colucci
authors.forename: Tony
authors.initials: T
authors.lastname: Yuen
authors.forename: Maria I
authors.initials: MI
authors.lastname: New
authors.forename: Alberta
authors.initials: A
authors.lastname: Zallone
authors.forename: Mone
authors.initials: M
authors.lastname: Zaidi
mesh_terms: D000818:Animals; D001127:Arginine Vasopressin / Q000378:metabolism*; D015153:Blotting, Western; D016723:Bone Remodeling / Q000502:physiology*; D001862:Bone Resorption / Q000209:etiology*; D004797:Enzyme-Linked Immunosorbent Assay; D006706:Homeostasis / Q000502:physiology*; D007010:Hyponatremia / Q000150:complications*; D051379:Mice; D018345:Mice, Knockout; D017483:Receptors, Vasopressin / Q000235:genetics
chemical_list: D017483:Receptors, Vasopressin; D001127:Arginine Vasopressin
keywords: osteopenia; oxytocin; pituitary hormone