Adiponectin receptor 1 regulates bone formation and osteoblast differentiation by GSK-3β/β-catenin signaling in mice.
Adiponectin and its receptors are expressed in bone marrow-derived osteoblasts. Previous studies in vivo and in vitro have produced controversial results. The purpose of this study was to use porcine adiponectin receptor 1 transgenic mice (pAdipoR1) as a model to evaluate the role of AdipoR1 on bone physiology at different ages. pAdipoR1 transgenic mice had higher bone mineral density than wild-type mice in both genders at 56 weeks of age. The bone volume and trabecular number, measured by micro-computed tomography (μCT) was significantly greater in transgenic than in wild-type female mice at both 8 and 56 weeks of age. ELISA analysis revealed that both serum osteocalcin and osteoprotegerin (OPG) were significantly increased in 8-week old pAdipoR1 transgenic mice of both genders. Furthermore, serum OPG was elevated at 32 and 56 weeks of age in female and male pAdipoR1 transgenic mice. Serum TRAP5b concentration was reduced in 8 and 56 weeks old male pAdipoR1 mice compared with wild-type male mice. Knock-down of AdipoR1 significantly decreased gene expression of osteocalcin, OPG, alkaline phosphatase and msh homeobox 2 and the mineralization in MC3T3-E1 cells and mesenchymal stem cells. In addition, pathscan analysis and real-time PCR analysis suggest AdipoR1 regulates osteoblast differentiation through GSK-3 β and β-Catenin signaling. Consequently, the lack of AdipoR1 impaired osteoblast differentiation and bone formation. We conclude that AdipoR1 is a critical factor for the osteoblast differentiation and bone homeostasis.
Department of Animal Science and Technology, National Taiwan University, Taipei, Taiwan.
Yuan Yu
YY
Lin
Department of Animal Science and Technology, National Taiwan University, Taipei, Taiwan.
Ching Yi
CY
Chen
Department of Athletics, National Taiwan University, Taipei, Taiwan.
Tai Yuan
TY
Chuang
Department of Animal Science and Technology, National Taiwan University, Taipei, Taiwan.
Yun
Y
Lin
Department of Animal Science and Technology, National Taiwan University, Taipei, Taiwan.
Hui Yu
HY
Liu
Department of Animal Science and Technology, National Taiwan University, Taipei, Taiwan.
Harry John
HJ
Mersmann
Department of Animal Science and Technology, National Taiwan University, Taipei, Taiwan; Institute of Biotechnology, National Taiwan University, Taipei, Taiwan.
Shinn Chih
SC
Wu
Department of Animal Science and Technology, National Taiwan University, Taipei, Taiwan; Institute of Biotechnology, National Taiwan University, Taipei, Taiwan. Electronic address: sding@ntu.edu.tw.
Shih Torng
ST
Ding
D016475:3T3 Cells; D000818:Animals; D001483:Base Sequence; D001846:Bone Development / Q000502:physiology*; D002454:Cell Differentiation / Q000502:physiology*; D017931:DNA Primers; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism*; D000071679:Glycogen Synthase Kinase 3 beta; D051379:Mice; D008822:Mice, Transgenic; D010006:Osteoblasts / Q000166:cytology* / Q000201:enzymology / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D054419:Receptors, Adiponectin / Q000502:physiology*; D015398:Signal Transduction; D055114:X-Ray Microtomography; D051176:beta Catenin / Q000378:metabolism*
D017931:DNA Primers; D054419:Receptors, Adiponectin; C475419:adiponectin receptor 1, mouse; D051176:beta Catenin; D000071679:Glycogen Synthase Kinase 3 beta; C000605507:Gsk3b protein, mouse; D038362:Glycogen Synthase Kinase 3
Adiponectin receptor 1; Bone turnover; GSK-3β; Osteoblast differentiation; β-Catenin