Display Settings:

Format

Send to:

Choose Destination
See comment in PubMed Commons below
Endocrinology. 2003 Dec;144(12):5138-44. Epub 2003 Aug 13.

Deletion of vitamin D receptor gene in mice results in abnormal skeletal muscle development with deregulated expression of myoregulatory transcription factors.

Author information

  • 1Department of Medicine and Bioregulatory Sciences, University of Tokushima Graduate School of Medicine, 3-18-15 Kuramoto-Cho, Tokushima 770-8503, Japan.

Abstract

Although rachitic/osteomalacic myopathy caused by impaired vitamin D actions has long been described, the molecular pathogenesis remains elusive. To determine physiological roles of vitamin D actions through vitamin D receptor (VDR) in skeletal muscle development, we examined skeletal muscle in VDR gene deleted (VDR -/-) mice, an animal model of vitamin D-dependent rickets type II, for morphological changes and expression of myoregulatory transcription factors and myosin heavy chain isoforms. We found that each muscle fiber was small and variable in size in hindlimb skeletal muscle from VDR -/- mice, although overall myocyte differentiation occurred normally. These abnormalities were independent of secondary metabolic changes such as hypocalcemia and hypophosphatemia, and were accompanied by aberrantly high and persistent expression of myf5, myogenin, E2A, and early myosin heavy chain isoforms, which are normally down-regulated at earlier stages. Moreover, treatment of VDR-positive myoblastic cells with 1,25(OH)2D3 in vitro caused down-regulation of these factors. These results suggest that VDR plays a physiological role in skeletal muscle development, participating in temporally strict down-regulation of myoregulatory transcription factors. The present study can form a molecular basis of VDR actions on muscle and should help further establish the physiological roles of VDR in muscle development as well as pharmacological effects of vitamin D on muscle functions.

Comment in

PMID:
12959989
[PubMed - indexed for MEDLINE]
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Icon for Atypon
    Loading ...
    Write to the Help Desk