Nmp4/CIZ: Road block at the intersection of PTH and load

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

Teriparatide (parathyroid hormone, [PTH]) is the only FDA-approved drug that replaces bone lost to osteoporosis. Enhancing PTH efficacy will improve cost-effectiveness and ameliorate contraindications. Combining this hormone with load-bearing exercise may enhance therapeutic potential consistent with a growing body of evidence that these agonists are synergistic and share common signaling pathways. Additionally, neutralizing molecules that naturally suppress the anabolic response to PTH may also improve the efficacy of treatment with this hormone. Nmp4/CIZ (nuclear matrix protein 4/cas interacting zinc finger)-null mice have enhanced responses to intermittent PTH with respect to increasing trabecular bone mass and are also immune to disuse-induced bone loss likely by the removal of Nmp4/CIZ suppressive action on osteoblast function. Nmp4/CIZ activity may be sensitive to changes in the mechanical environment of the bone cell brought about by hormone- or mechanical load-induced changes in cell shape and adhesion. Nmp4 was identified in a screen for PTH-responsive nuclear matrix architectural transcription factors (ATFs) that we proposed translate hormone-induced changes in cell shape and adhesion into changes in target gene DNA conformation. CIZ was independently identified as a nucleocytoplasmic shuttling transcription factor associating with the mechano-sensitive focal adhesion proteins p130Cas and zxyin. The p130Cas/zyxin/Nmp4/CIZ pathway resembles the β-catenin/TCF/LEF1 mechanotransduction response limb and both share features with the HMGB1 (high mobility group box 1)/RAGE (receptor for advanced glycation end products) signaling axis. Here we describe Nmp4/CIZ within the context of the PTH-induced anabolic response and consider the place of this molecule in the hierarchy of the PTH-load response network.

Original languageEnglish
Pages (from-to)259-266
Number of pages8
JournalBone
Volume46
Issue number2
DOIs
StatePublished - Feb 2010

Fingerprint

Nuclear Matrix-Associated Proteins
Zinc Fingers
Parathyroid Hormone
Hormones
Cell Shape
Bone and Bones
Cell Adhesion
Zyxin
Crk-Associated Substrate Protein
Transcription Factors
Teriparatide
Nucleic Acid Conformation
Nuclear Matrix
Catenins
Focal Adhesions
Weight-Bearing
Osteoblasts
Osteoporosis
Cost-Benefit Analysis
Extremities

Keywords

  • Architectural transcription factor
  • Mechanosome
  • Nuclear matrix
  • Osteoblast
  • Osteoporosis

ASJC Scopus subject areas

  • Physiology
  • Endocrinology, Diabetes and Metabolism
  • Histology

Cite this

Nmp4/CIZ : Road block at the intersection of PTH and load. / Childress, Paul; Robling, Alexander; Bidwell, Joseph.

In: Bone, Vol. 46, No. 2, 02.2010, p. 259-266.

Research output: Contribution to journalArticle

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