Nmp4/CIZ suppresses parathyroid hormone-induced increases in trabecular bone

Alexander G. Robling, Paul Childress, Jun Yu, Jessica Cotte, Aaron Heller, Binu K. Philip, Joseph P. Bidwell

Research output: Contribution to journalArticle

24 Scopus citations

Abstract

The nucleocytoplasmic shuttling transcription factor Nmp4/CIZ (nuclear matrix protein 4/cas interacting zinc finger protein) is a ubiquitously expressed protein that regulates both cytoplasmic and nuclear activities. In the nucleus, Nmp4/CIZ represses transcription of genes crucial to osteoblast differentiation and genes activated by various anabolic stimuli, including parathyroid hormone (PTH). We investigated the role of Nmp4/CIZ in the PTH-induced increase in bone by engineering mice with loss-of-function mutations in the Nmp4/CIZ gene, and treating 10-week-old female mice with anabolic doses of human PTH (1-34) at 30 μg/kg/day, 7 day/week, for 7 weeks or vehicle control. The untreated, baseline phenotype of the Nmp4-null mice between 8 and 16 weeks of age included a modest but significant increase in bone mineral density (BMD) and bone mineral content (BMC) compared to wild-type (WT) mice. Type I collagen mRNA expression was moderately elevated in the femurs of the Nmp4-null mice. The Nmp4 mutant alleles decreased body weight by 4% when expressed on a mixed background but the same alleles on a pure B6 background yielded a significant, 15% increase in body weight among the KO mice, compared to their WT controls. Hormone treatment equally enhanced BMD and BMC over vehicle-treated mice in both the WT and Nmp4-null groups but Nmp4-KO mice exhibited a significantly greater PTH-induced acquisition of femoral trabecular bone as compared to WT mice. These data support our hypothesis that Nmp4/CIZ is a transcriptional attenuator that suppresses osteoid synthesis and PTH-mediated acquisition of cancellous bone.

Original languageEnglish (US)
Pages (from-to)734-743
Number of pages10
JournalJournal of cellular physiology
Volume219
Issue number3
DOIs
StatePublished - Jun 1 2009

ASJC Scopus subject areas

  • Physiology
  • Clinical Biochemistry
  • Cell Biology

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