Overexpression of secreted frizzled-related protein 1 inhibits bone formation and attenuates parathyroid hormone bone anabolic effects

Wei Yao, Zhiqiang Cheng, Mohammad Shahnazari, Wewei Dai, Mark L. Johnson, Nancy E Lane

Research output: Contribution to journalArticle

65 Citations (Scopus)

Abstract

Secreted frizzled-related protein 1 (sFRP1) is an antagonist of Wnt signaling, an important pathway in maintaining bone homeostasis. In this study we evaluated the skeletal phenotype of mice overexpressing sFRP1 (sFRP1 Tg) and the interaction of parathyroid hormone (PTH) treatment and sFRP1 (over)expression. Bone mass and microarchitecture were measured by micro-computed tomography (μCT). Osteoblastic and osteoclastic cell maturation and function were assessed in primary bone marrow cell cultures. Bone turnover was assessed by biochemical markers and dynamic bone histomorphometry. Real-time PCR was used to monitor the expression of several genes that regulate osteoblast maturation and function in whole bone. We found that trabecular bone mass measurements in distal femurs and lumbar vertebral bodies were 22% and 51% lower in female and 9% and 33% lower in male sFRP1 Tg mice, respectively, compared with wild-type (WT) controls at 3 months of age. Genes associated with osteoblast maturation and function, serum bone formation markers, and surface based bone formation were significantly decreased in sFRP1 Tg mice of both sexes. Bone resorption was similar between sFRP1 Tg and WT females and was higher in sFRP1 Tg male mice. Treatment with hPTH(1-34) (40μg/kg/d) for 2 weeks increased trabecular bone volume in WT mice (females: +30% to 50%; males: +35% to 150%) compared with sFRP1 Tg mice (females: +5%; males: +18% to 54%). Percentage increases in bone formation also were lower in PTH-treated sFRP1 Tg mice compared with PTH-treated WT mice. In conclusion, overexpression of sFRP1 inhibited bone formation as well as attenuated PTH anabolic action on bone. The gender differences in the bone phenotype of the sFRP1 Tg animal warrants further investigation.

Original languageEnglish (US)
Pages (from-to)190-199
Number of pages10
JournalJournal of Bone and Mineral Research
Volume25
Issue number2
DOIs
StatePublished - Feb 2010

Fingerprint

Anabolic Agents
Parathyroid Hormone
Osteogenesis
Bone and Bones
Osteoblasts
frizzled related protein-1
Teriparatide
Phenotype
Wnt Signaling Pathway
Bone Remodeling
Bone Resorption
Bone Marrow Cells
Femur
Real-Time Polymerase Chain Reaction
Homeostasis

Keywords

  • Bone mass
  • PTH
  • Sex difference
  • sFRP1
  • Transgenic

ASJC Scopus subject areas

  • Orthopedics and Sports Medicine
  • Endocrinology, Diabetes and Metabolism

Cite this

Overexpression of secreted frizzled-related protein 1 inhibits bone formation and attenuates parathyroid hormone bone anabolic effects. / Yao, Wei; Cheng, Zhiqiang; Shahnazari, Mohammad; Dai, Wewei; Johnson, Mark L.; Lane, Nancy E.

In: Journal of Bone and Mineral Research, Vol. 25, No. 2, 02.2010, p. 190-199.

Research output: Contribution to journalArticle

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