title: Bone Mass and Strength are Significantly Improved in Mice Overexpressing Human WNT16 in Osteocytes.
abstract: Recently, we demonstrated that osteoblast-specific overexpression of human WNT16 increased both cortical and trabecular bone mass and structure in mice. To further identify the cell-specific role of Wnt16 in bone homeostasis, we created transgenic (TG) mice overexpressing human WNT16 in osteocytes using Dmp1 promoter (Dmp1-hWNT16 TG) on C57BL/6 (B6) background. We analyzed bone phenotypes and serum bone biomarkers, performed gene expression analysis and measured dynamic bone histomorphometry in Dmp1-hWNT16 TG and wild-type (WT) mice. Compared to WT mice, Dmp1-hWNT16 TG mice exhibited significantly higher whole-body, spine and femoral aBMD, BMC and trabecular (BV/TV, Tb.N, and Tb.Th) and cortical (bone area and thickness) parameters in both male and female at 12 weeks of age. Femur stiffness and ultimate force were also significantly improved in the Dmp1-hWNT16 TG female mice, compared to sex-matched WT littermates. In addition, female Dmp1-hWNT16 TG mice displayed significantly higher MS/BS, MAR and BFR/BS compared to the WT mice. Gene expression analysis demonstrated significantly higher mRNA level of Alp in both male and female Dmp1-hWNT16 TG mice and significantly higher levels of Osteocalcin, Opg and Rankl in the male Dmp1-hWNT16 TG mice in bone tissue compared to sex-matched WT mice. These results indicate that WNT16 plays a critical role for acquisition of both cortical and trabecular bone mass and strength. Strategies designed to use WNT16 as a target for therapeutic interventions will be valuable to treat osteoporosis and other low bone mass conditions.
authors.affiliation: Division of Endocrinology, Department of Medicine, Indiana University School of Medicine, 1120 West Michigan St, CL459, Indianapolis, IN, 46202, USA. ialam@iu.edu.
authors.forename: Imranul
authors.initials: I
authors.lastname: Alam
authors.affiliation: Division of Endocrinology, Department of Medicine, Indiana University School of Medicine, 1120 West Michigan St, CL459, Indianapolis, IN, 46202, USA.
authors.forename: Austin M
authors.initials: AM
authors.lastname: Reilly
authors.affiliation: Division of Endocrinology, Department of Medicine, Indiana University School of Medicine, 1120 West Michigan St, CL459, Indianapolis, IN, 46202, USA.
authors.forename: Mohammed
authors.initials: M
authors.lastname: Alkhouli
authors.affiliation: Division of Endocrinology, Department of Medicine, Indiana University School of Medicine, 1120 West Michigan St, CL459, Indianapolis, IN, 46202, USA.
authors.forename: Rita L
authors.initials: RL
authors.lastname: Gerard-O'Riley
authors.affiliation: Division of Endocrinology, Department of Medicine, Indiana University School of Medicine, 1120 West Michigan St, CL459, Indianapolis, IN, 46202, USA.
authors.forename: Charishma
authors.initials: C
authors.lastname: Kasipathi
authors.affiliation: Division of Endocrinology, Department of Medicine, Indiana University School of Medicine, 1120 West Michigan St, CL459, Indianapolis, IN, 46202, USA.
authors.forename: Dana K
authors.initials: DK
authors.lastname: Oakes
authors.affiliation: Division of Endocrinology, Department of Medicine, Indiana University School of Medicine, 1120 West Michigan St, CL459, Indianapolis, IN, 46202, USA.
authors.forename: Weston B
authors.initials: WB
authors.lastname: Wright
authors.affiliation: Division of Endocrinology, Department of Medicine, Indiana University School of Medicine, 1120 West Michigan St, CL459, Indianapolis, IN, 46202, USA.
authors.forename: Dena
authors.initials: D
authors.lastname: Acton
authors.affiliation: Division of Endocrinology, Department of Medicine, Indiana University School of Medicine, 1120 West Michigan St, CL459, Indianapolis, IN, 46202, USA.
authors.forename: Amie K
authors.initials: AK
authors.lastname: McQueen
authors.affiliation: Division of Endocrinology, Department of Medicine, Indiana University School of Medicine, 1120 West Michigan St, CL459, Indianapolis, IN, 46202, USA.
authors.forename: Bhavmik
authors.initials: B
authors.lastname: Patel
authors.affiliation: Department of Anatomy and Cell Biology, Indiana University School of Medicine, Indianapolis, IN, USA.
authors.forename: Kyung-Eun
authors.initials: KE
authors.lastname: Lim
authors.affiliation: Department of Anatomy and Cell Biology, Indiana University School of Medicine, Indianapolis, IN, USA.
authors.forename: Alexander G
authors.initials: AG
authors.lastname: Robling
authors.affiliation: Division of Endocrinology, Department of Medicine, Indiana University School of Medicine, 1120 West Michigan St, CL459, Indianapolis, IN, 46202, USA.|Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN, USA.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Econs
mesh_terms: D000818:Animals; D015519:Bone Density / Q000235:genetics / Q000502:physiology*; D001842:Bone and Bones / Q000378:metabolism; D005260:Female; D005269:Femur / Q000378:metabolism / Q000473:pathology; D006801:Humans; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D010006:Osteoblasts / Q000378:metabolism; D015675:Osteocalcin / Q000378:metabolism; D010011:Osteocytes / Q000378:metabolism*; D010024:Osteoporosis / Q000235:genetics / Q000378:metabolism; D051153:Wnt Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: C417262:WNT16 protein, human; D051153:Wnt Proteins; C585687:Wnt16 protein, mouse; D015675:Osteocalcin
keywords: Bone mass; Gene; Osteocyte; Osteoporosis; Transgenic; WNT16