title: Functions of vasopressin and oxytocin in bone mass regulation.
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.
authors.affiliation: The Mount Sinai Bone Program, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY 10029;
authors.forename: Li
authors.initials: L
authors.lastname: Sun
authors.affiliation: Department of Basic Medical Science, Neurosciences and Sensory Organs, University of Bari, 70124 Bari, Italy;
authors.forename: Roberto
authors.initials: R
authors.lastname: Tamma
authors.affiliation: The Mount Sinai Bone Program, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY 10029;
authors.forename: Tony
authors.initials: T
authors.lastname: Yuen
authors.affiliation: Department of Basic Medical Science, Neurosciences and Sensory Organs, University of Bari, 70124 Bari, Italy;
authors.forename: Graziana
authors.initials: G
authors.lastname: Colaianni
authors.affiliation: The Mount Sinai Bone Program, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY 10029;
authors.forename: Yaoting
authors.initials: Y
authors.lastname: Ji
authors.affiliation: Department of Basic Medical Science, Neurosciences and Sensory Organs, University of Bari, 70124 Bari, Italy;
authors.forename: Concetta
authors.initials: C
authors.lastname: Cuscito
authors.affiliation: The Mount Sinai Bone Program, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY 10029;
authors.forename: Jack
authors.initials: J
authors.lastname: Bailey
authors.affiliation: The Mount Sinai Bone Program, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY 10029;
authors.forename: Samarth
authors.initials: S
authors.lastname: Dhawan
authors.affiliation: The Mount Sinai Bone Program, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY 10029;
authors.forename: Ping
authors.initials: P
authors.lastname: Lu
authors.affiliation: Department of Chemistry, University of Bari Aldo Moro, Bari 70124, Italy;
authors.forename: Cosima D
authors.initials: CD
authors.lastname: Calvano
authors.affiliation: The Mount Sinai Bone Program, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY 10029;
authors.forename: Ling-Ling
authors.initials: LL
authors.lastname: Zhu
authors.affiliation: Department of Chemistry, University of Bari Aldo Moro, Bari 70124, Italy;
authors.forename: Carlo G
authors.initials: CG
authors.lastname: Zambonin
authors.affiliation: Department of Clinical and Experimental Medicine, University of Foggia, Foggia 71122, Italy.
authors.forename: Adriana
authors.initials: A
authors.lastname: Di Benedetto
authors.affiliation: The Mount Sinai Bone Program, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY 10029;
authors.forename: Agnes
authors.initials: A
authors.lastname: Stachnik
authors.affiliation: The Mount Sinai Bone Program, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY 10029;
authors.forename: Peng
authors.initials: P
authors.lastname: Liu
authors.affiliation: Department of Basic Medical Science, Neurosciences and Sensory Organs, University of Bari, 70124 Bari, Italy;
authors.forename: Maria
authors.initials: M
authors.lastname: Grano
authors.affiliation: Department of Basic Medical Science, Neurosciences and Sensory Organs, University of Bari, 70124 Bari, Italy;
authors.forename: Silvia
authors.initials: S
authors.lastname: Colucci
authors.affiliation: The Mount Sinai Bone Program, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY 10029;
authors.forename: Terry F
authors.initials: TF
authors.lastname: Davies
authors.affiliation: 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.
authors.forename: Maria I
authors.initials: MI
authors.lastname: New
authors.affiliation: Department of Basic Medical Science, Neurosciences and Sensory Organs, University of Bari, 70124 Bari, Italy;
authors.forename: Alberta
authors.initials: A
authors.lastname: Zallone
authors.affiliation: 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.
authors.forename: Mone
authors.initials: M
authors.lastname: Zaidi
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001127:Arginine Vasopressin / Q000494:pharmacology / Q000502:physiology*; D015153:Blotting, Western; D015519:Bone Density / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D001851:Bone Diseases, Metabolic / Q000235:genetics; D016723:Bone Remodeling / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D017353:Gene Deletion; D051379:Mice; D008817:Mice, Mutant Strains; D008969:Molecular Sequence Data; D010006:Osteoblasts / Q000378:metabolism / Q000502:physiology; D010012:Osteogenesis / Q000235:genetics / Q000502:physiology*; D010121:Oxytocin / Q000494:pharmacology / Q000502:physiology*; D018045:Receptors, Oxytocin / Q000235:genetics / Q000378:metabolism; D017483:Receptors, Vasopressin / Q000235:genetics / Q000378:metabolism*
chemical_list: C000600609:AVPR1a receptor, mouse; D018045:Receptors, Oxytocin; D017483:Receptors, Vasopressin; D001127:Arginine Vasopressin; D010121:Oxytocin
keywords: osteoblast; osteoporosis; skeleton