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

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

Research output: Contribution to journalArticle

23 Citations (Scopus)

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
Pages (from-to)734-743
Number of pages10
JournalJournal of Cellular Physiology
Volume219
Issue number3
DOIs
StatePublished - Jun 2009

Fingerprint

Nuclear Matrix-Associated Proteins
Zinc Fingers
Parathyroid Hormone
Zinc
Bone
Minerals
Bone Density
Proteins
Genes
Bone and Bones
Teriparatide
Alleles
Body Weight
Osteoblasts
Transcription
Collagen Type I
Cancellous Bone
Transcription Factors
Thigh
Femur

ASJC Scopus subject areas

  • Clinical Biochemistry
  • Cell Biology
  • Physiology

Cite this

Nmp4/CIZ suppresses parathyroid hormone-induced increases in trabecular bone. / Robling, Alexander; Childress, Paul; Yu, Jun; Cotte, Jessica; Heller, Aaron; Philip, Binu K.; Bidwell, Joseph.

In: Journal of Cellular Physiology, Vol. 219, No. 3, 06.2009, p. 734-743.

Research output: Contribution to journalArticle

Robling, Alexander ; Childress, Paul ; Yu, Jun ; Cotte, Jessica ; Heller, Aaron ; Philip, Binu K. ; Bidwell, Joseph. / Nmp4/CIZ suppresses parathyroid hormone-induced increases in trabecular bone. In: Journal of Cellular Physiology. 2009 ; Vol. 219, No. 3. pp. 734-743.
@article{39c51a0149b640cab3390dbb6a840c7e,
title = "Nmp4/CIZ suppresses parathyroid hormone-induced increases in trabecular bone",
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.",
author = "Alexander Robling and Paul Childress and Jun Yu and Jessica Cotte and Aaron Heller and Philip, {Binu K.} and Joseph Bidwell",
year = "2009",
month = "6",
doi = "10.1002/jcp.21717",
language = "English",
volume = "219",
pages = "734--743",
journal = "Journal of Cellular Physiology",
issn = "0021-9541",
publisher = "Wiley-Liss Inc.",
number = "3",

}

TY - JOUR

T1 - Nmp4/CIZ suppresses parathyroid hormone-induced increases in trabecular bone

AU - Robling, Alexander

AU - Childress, Paul

AU - Yu, Jun

AU - Cotte, Jessica

AU - Heller, Aaron

AU - Philip, Binu K.

AU - Bidwell, Joseph

PY - 2009/6

Y1 - 2009/6

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=64549109378&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=64549109378&partnerID=8YFLogxK

U2 - 10.1002/jcp.21717

DO - 10.1002/jcp.21717

M3 - Article

C2 - 19189321

AN - SCOPUS:64549109378

VL - 219

SP - 734

EP - 743

JO - Journal of Cellular Physiology

JF - Journal of Cellular Physiology

SN - 0021-9541

IS - 3

ER -