title: Reduced Bone Density and Cortical Bone Indices in Female Adiponectin-Knockout Mice.
abstract: A positive association between fat and bone mass is maintained through a network of signaling molecules. Clinical studies found that the circulating levels of adiponectin, a peptide secreted from adipocytes, are inversely related to visceral fat mass and bone mineral density, and it has been suggested that adiponectin contributes to the coupling between fat and bone. Our study tested the hypothesis that adiponectin affects bone tissue by comparing the bone phenotype of wild-type and adiponectin-knockout (APN-KO) female mice between the ages of 8-37 weeks. Using a longitudinal study design, we determined body composition and bone density using dual energy x-ray absorptiometry. In parallel, groups of animals were killed at different ages and bone properties were analyzed by microcomputed tomography, dynamic histomorphometry, 3-point bending test, nanoindentation, and computational modelling. APN-KO mice had reduced body fat and decreased whole-skeleton bone mineral density. Microcomputed tomography analysis identified reduced cortical area fraction and average cortical thickness in APN-KO mice in all the age groups and reduced trabecular bone volume fraction only in young APN-KO mice. There were no major differences in bone strength and material properties between the 2 groups. Taken together, our results demonstrate a positive effect of adiponectin on bone geometry and density in our mouse model. Assuming adiponectin has similar effects in humans, the low circulating levels of adiponectin associated with increased fat mass are unlikely to contribute to the parallel increase in bone mass. Therefore, adiponectin does not appear to play a role in the coupling between fat and bone tissue.
authors.affiliation: Department of Medicine (D.N., M.W., K.E.C., D.T., D.S.M., A.J.C., G.D.G., A.G., J.C.), University of Auckland, Auckland 1142, New Zealand; Auckland Bioengineering Institute (D.S., J.F.), University of Auckland, Auckland 1142, New Zealand; Department of Engineering Science (J.F.), University of Auckland, Auckland 1142, New Zealand; and Department of Chemical and Materials Engineering (P.T.T., M.D.), University of Auckland, Auckland 1142, New Zealand.
authors.forename: Dorit
authors.initials: D
authors.lastname: Naot
authors.affiliation: Department of Medicine (D.N., M.W., K.E.C., D.T., D.S.M., A.J.C., G.D.G., A.G., J.C.), University of Auckland, Auckland 1142, New Zealand; Auckland Bioengineering Institute (D.S., J.F.), University of Auckland, Auckland 1142, New Zealand; Department of Engineering Science (J.F.), University of Auckland, Auckland 1142, New Zealand; and Department of Chemical and Materials Engineering (P.T.T., M.D.), University of Auckland, Auckland 1142, New Zealand.
authors.forename: Maureen
authors.initials: M
authors.lastname: Watson
authors.affiliation: Department of Medicine (D.N., M.W., K.E.C., D.T., D.S.M., A.J.C., G.D.G., A.G., J.C.), University of Auckland, Auckland 1142, New Zealand; Auckland Bioengineering Institute (D.S., J.F.), University of Auckland, Auckland 1142, New Zealand; Department of Engineering Science (J.F.), University of Auckland, Auckland 1142, New Zealand; and Department of Chemical and Materials Engineering (P.T.T., M.D.), University of Auckland, Auckland 1142, New Zealand.
authors.forename: Karen E
authors.initials: KE
authors.lastname: Callon
authors.affiliation: Department of Medicine (D.N., M.W., K.E.C., D.T., D.S.M., A.J.C., G.D.G., A.G., J.C.), University of Auckland, Auckland 1142, New Zealand; Auckland Bioengineering Institute (D.S., J.F.), University of Auckland, Auckland 1142, New Zealand; Department of Engineering Science (J.F.), University of Auckland, Auckland 1142, New Zealand; and Department of Chemical and Materials Engineering (P.T.T., M.D.), University of Auckland, Auckland 1142, New Zealand.
authors.forename: Donna
authors.initials: D
authors.lastname: Tuari
authors.affiliation: Department of Medicine (D.N., M.W., K.E.C., D.T., D.S.M., A.J.C., G.D.G., A.G., J.C.), University of Auckland, Auckland 1142, New Zealand; Auckland Bioengineering Institute (D.S., J.F.), University of Auckland, Auckland 1142, New Zealand; Department of Engineering Science (J.F.), University of Auckland, Auckland 1142, New Zealand; and Department of Chemical and Materials Engineering (P.T.T., M.D.), University of Auckland, Auckland 1142, New Zealand.
authors.forename: David S
authors.initials: DS
authors.lastname: Musson
authors.affiliation: Department of Medicine (D.N., M.W., K.E.C., D.T., D.S.M., A.J.C., G.D.G., A.G., J.C.), University of Auckland, Auckland 1142, New Zealand; Auckland Bioengineering Institute (D.S., J.F.), University of Auckland, Auckland 1142, New Zealand; Department of Engineering Science (J.F.), University of Auckland, Auckland 1142, New Zealand; and Department of Chemical and Materials Engineering (P.T.T., M.D.), University of Auckland, Auckland 1142, New Zealand.
authors.forename: Ally J
authors.initials: AJ
authors.lastname: Choi
authors.affiliation: Department of Medicine (D.N., M.W., K.E.C., D.T., D.S.M., A.J.C., G.D.G., A.G., J.C.), University of Auckland, Auckland 1142, New Zealand; Auckland Bioengineering Institute (D.S., J.F.), University of Auckland, Auckland 1142, New Zealand; Department of Engineering Science (J.F.), University of Auckland, Auckland 1142, New Zealand; and Department of Chemical and Materials Engineering (P.T.T., M.D.), University of Auckland, Auckland 1142, New Zealand.
authors.forename: Dharshini
authors.initials: D
authors.lastname: Sreenivasan
authors.affiliation: Department of Medicine (D.N., M.W., K.E.C., D.T., D.S.M., A.J.C., G.D.G., A.G., J.C.), University of Auckland, Auckland 1142, New Zealand; Auckland Bioengineering Institute (D.S., J.F.), University of Auckland, Auckland 1142, New Zealand; Department of Engineering Science (J.F.), University of Auckland, Auckland 1142, New Zealand; and Department of Chemical and Materials Engineering (P.T.T., M.D.), University of Auckland, Auckland 1142, New Zealand.
authors.forename: Justin
authors.initials: J
authors.lastname: Fernandez
authors.affiliation: Department of Medicine (D.N., M.W., K.E.C., D.T., D.S.M., A.J.C., G.D.G., A.G., J.C.), University of Auckland, Auckland 1142, New Zealand; Auckland Bioengineering Institute (D.S., J.F.), University of Auckland, Auckland 1142, New Zealand; Department of Engineering Science (J.F.), University of Auckland, Auckland 1142, New Zealand; and Department of Chemical and Materials Engineering (P.T.T., M.D.), University of Auckland, Auckland 1142, New Zealand.
authors.forename: Pao Ting
authors.initials: PT
authors.lastname: Tu
authors.affiliation: Department of Medicine (D.N., M.W., K.E.C., D.T., D.S.M., A.J.C., G.D.G., A.G., J.C.), University of Auckland, Auckland 1142, New Zealand; Auckland Bioengineering Institute (D.S., J.F.), University of Auckland, Auckland 1142, New Zealand; Department of Engineering Science (J.F.), University of Auckland, Auckland 1142, New Zealand; and Department of Chemical and Materials Engineering (P.T.T., M.D.), University of Auckland, Auckland 1142, New Zealand.
authors.forename: Michelle
authors.initials: M
authors.lastname: Dickinson
authors.affiliation: Department of Medicine (D.N., M.W., K.E.C., D.T., D.S.M., A.J.C., G.D.G., A.G., J.C.), University of Auckland, Auckland 1142, New Zealand; Auckland Bioengineering Institute (D.S., J.F.), University of Auckland, Auckland 1142, New Zealand; Department of Engineering Science (J.F.), University of Auckland, Auckland 1142, New Zealand; and Department of Chemical and Materials Engineering (P.T.T., M.D.), University of Auckland, Auckland 1142, New Zealand.
authors.forename: Greg D
authors.initials: GD
authors.lastname: Gamble
authors.affiliation: Department of Medicine (D.N., M.W., K.E.C., D.T., D.S.M., A.J.C., G.D.G., A.G., J.C.), University of Auckland, Auckland 1142, New Zealand; Auckland Bioengineering Institute (D.S., J.F.), University of Auckland, Auckland 1142, New Zealand; Department of Engineering Science (J.F.), University of Auckland, Auckland 1142, New Zealand; and Department of Chemical and Materials Engineering (P.T.T., M.D.), University of Auckland, Auckland 1142, New Zealand.
authors.forename: Andrew
authors.initials: A
authors.lastname: Grey
authors.affiliation: Department of Medicine (D.N., M.W., K.E.C., D.T., D.S.M., A.J.C., G.D.G., A.G., J.C.), University of Auckland, Auckland 1142, New Zealand; Auckland Bioengineering Institute (D.S., J.F.), University of Auckland, Auckland 1142, New Zealand; Department of Engineering Science (J.F.), University of Auckland, Auckland 1142, New Zealand; and Department of Chemical and Materials Engineering (P.T.T., M.D.), University of Auckland, Auckland 1142, New Zealand.
authors.forename: Jillian
authors.initials: J
authors.lastname: Cornish
mesh_terms: D017667:Adipocytes / Q000502:physiology; D052242:Adiponectin / Q000502:physiology*; D050154:Adiposity; D000818:Animals; D015519:Bone Density; D001854:Bone Marrow Cells / Q000502:physiology; D000071556:Cancellous Bone / Q000502:physiology; D003198:Computer Simulation; D000071538:Cortical Bone / Q000502:physiology*; D005260:Female; D018345:Mice, Knockout; D008954:Models, Biological
chemical_list: D052242:Adiponectin