S-Space College of Medicine/School of Medicine (의과대학/대학원) Internal Medicine (내과학전공) Journal Papers (저널논문_내과학전공)
Transgenic mice overexpressing secreted frizzled-related proteins (sFRP)4 under the control of serum amyloid P promoter exhibit low bone mass but did not result in disturbed phosphate homeostasis
- Cho, Hwa Young; Choi, Hyung Jin; Sun, Hyun Jin; Yang, Jae-Yeon; Cho, Sun Wook; Kim, Seong Yeon; Shin, Chan Soo; Kim, Jung Eun; Kim, Sang Wan; An, Jee Hyun
- Issue Date
- ELSEVIER SCIENCE INC
- BONE; Vol.47 2; 263-271
- Secreted frizzled-related protein; Phosphatonin; Wnt signaling; Osteoblast; Bone formation; Transgenic mouse
- Secreted frizzled-related protein-4 (sFRP4) is a member of secreted modulators of Wnt signaling pathways and has been recognized to play important role in the pathogenesis of oncogenic osteomalacia as a potential phosphatonin. To investigate the role of sFRP4 in bone biology and phosphorus homeostasis in postnatal life, we generated transgenic mice that overexpress sFRP4 under the control of the serum amyloid P promoter (SAP-sFRP4), which drives transgene expression postnatally. Serum phosphorus level and urinary phosphorus excretion were slightly lower and higher, respectively, in SAP-sFRP4 compared to wild-type (WT) littermate, but the difference did not reach statistical significance. However, renal Na(+/-)/Pi cotransporter (Npt) 2a and 1 alpha-hydroxylase gene expression were up-regulated in SAP-sFRP4 mice. In addition, the level of serum 1,25-dihydroxyvitamin D(3) was higher in SAP-sFRP4 mice. At 5 weeks of age, bone mineral density (BMD) in SAP-sFRP4 was similar to that in WT. However, with advancing age, SAP-sFRP4 mice gained less BMD so that areal BMD of SAP-sFRP4 mice was significantly lower compared to WT at 15 weeks of age. Histomorphometric analysis of proximal tibia showed that trabecular bone volume (BV/TV) and thickness (Tb center dot Th) were significantly lower in SAP-sFRP4 mice. There was no evidence of osteomalacia in histological analysis. Our data do not support the role of sFRP4 per se as a phosphatonin but suggest that sFRP4 negatively regulates bone formation without disrupting phosphorus homeostasis. (C) 2010 Elsevier Inc. All rights reserved.
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