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

Hwa Young Cho, Hyung Jin Choi, Hyun Jin Sun, Jae Yeon Yang, Jee Hyun An, Sun Wook Cho, Sang Wan Kim, Seong Yeon Kim, Jung Eun Kim, Chan Soo Shin

Research output: Contribution to journalArticlepeer-review

32 Scopus citations

Abstract

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 co-transporter (Npt) 2a and 1α-hydroxylase gene expression were up-regulated in SAP-sFRP4 mice. In addition, the level of serum 1,25-dihydroxyvitamin D3 was higher in SAP-sFRP4 mice. At 5weeks 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 15weeks of age. Histomorphometric analysis of proximal tibia showed that trabecular bone volume (BV/TV) and thickness (Tb.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.

Original languageEnglish
Pages (from-to)263-271
Number of pages9
JournalBone
Volume47
Issue number2
DOIs
StatePublished - Aug 2010

Keywords

  • Bone formation
  • Osteoblast
  • Phosphatonin
  • Secreted frizzled-related protein
  • Transgenic mouse
  • Wnt signaling

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