Bone Mass and Strength are Significantly Improved in Mice Overexpressing Human WNT16 in Osteocytes

Imranul Alam, Austin M. Reilly, Mohammed Alkhouli, Rita L. Gerard-O’Riley, Charishma Kasipathi, Dana K. Oakes, Weston B. Wright, Dena Acton, Amie K. McQueen, Bhavmik Patel, Kyung Eun Lim, Alexander Robling, Michael Econs

Research output: Contribution to journalArticle

4 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)1-13
Number of pages13
JournalCalcified Tissue International
DOIs
StateAccepted/In press - Dec 24 2016

Fingerprint

Osteocytes
Transgenic Mice
Bone and Bones
Gene Expression
Osteocalcin
Thigh
Osteoblasts
Femur
Osteoporosis
Spine
Homeostasis
Biomarkers
Phenotype
Messenger RNA
Serum

Keywords

  • Bone mass
  • Gene
  • Osteocyte
  • Osteoporosis
  • Transgenic
  • WNT16

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Orthopedics and Sports Medicine
  • Endocrinology

Cite this

Bone Mass and Strength are Significantly Improved in Mice Overexpressing Human WNT16 in Osteocytes. / Alam, Imranul; Reilly, Austin M.; Alkhouli, Mohammed; Gerard-O’Riley, Rita L.; Kasipathi, Charishma; Oakes, Dana K.; Wright, Weston B.; Acton, Dena; McQueen, Amie K.; Patel, Bhavmik; Lim, Kyung Eun; Robling, Alexander; Econs, Michael.

In: Calcified Tissue International, 24.12.2016, p. 1-13.

Research output: Contribution to journalArticle

Alam, I, Reilly, AM, Alkhouli, M, Gerard-O’Riley, RL, Kasipathi, C, Oakes, DK, Wright, WB, Acton, D, McQueen, AK, Patel, B, Lim, KE, Robling, A & Econs, M 2016, 'Bone Mass and Strength are Significantly Improved in Mice Overexpressing Human WNT16 in Osteocytes', Calcified Tissue International, pp. 1-13. https://doi.org/10.1007/s00223-016-0225-4
Alam, Imranul ; Reilly, Austin M. ; Alkhouli, Mohammed ; Gerard-O’Riley, Rita L. ; Kasipathi, Charishma ; Oakes, Dana K. ; Wright, Weston B. ; Acton, Dena ; McQueen, Amie K. ; Patel, Bhavmik ; Lim, Kyung Eun ; Robling, Alexander ; Econs, Michael. / Bone Mass and Strength are Significantly Improved in Mice Overexpressing Human WNT16 in Osteocytes. In: Calcified Tissue International. 2016 ; pp. 1-13.
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AU - Kasipathi, Charishma

AU - Oakes, Dana K.

AU - Wright, Weston B.

AU - Acton, Dena

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