論文 - 詳細
| RRC ID | 41959 |
|---|---|
| 著者 | Endo I, Inoue D, Mitsui T, Umaki Y, Akaike M, Yoshizawa T, Kato S, Matsumoto T. |
| タイトル | Deletion of vitamin D receptor gene in mice results in abnormal skeletal muscle development with deregulated expression of myoregulatory transcription factors. |
| ジャーナル | Endocrinology |
| 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. |
| 巻・号 | 144(12) |
| ページ | 5138-44 |
| 公開日 | 2003-12-1 |
| DOI | 10.1210/en.2003-0502 |
| PII | en.2003-0502 |
| PMID | 12959989 |
| MeSH | Animals DNA-Binding Proteins* Disease Models, Animal Gene Expression Regulation, Developmental / drug effects Gene Expression Regulation, Developmental / physiology In Vitro Techniques Mice Mice, Knockout Muscle Proteins / metabolism* Muscle, Skeletal / abnormalities* Muscle, Skeletal / cytology Muscle, Skeletal / physiology* Myogenic Regulatory Factor 5 Myogenin / metabolism Receptors, Calcitriol / genetics* Receptors, Calcitriol / metabolism Rickets / genetics Rickets / metabolism Rickets / physiopathology Trans-Activators* Transcription Factors / metabolism* Vitamin D / analogs & derivatives* Vitamin D / pharmacology |
| IF | 3.934 |
| 引用数 | 256 |
| WOS 分野 | ENDOCRINOLOGY & METABOLISM |
| オルトメトリクス指標 |
オルトメトリクス指標項目
|
| 最多言及媒体 | News |
| 各媒体での言及数の合計 | 17 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| ヒト・動物細胞 | C2C12(RCB0987) |