論文 - 詳細
| RRC ID | 62077 |
|---|---|
| 著者 | Laurie LE, Kokubo H, Nakamura M, Saga Y, Funato N. |
| タイトル | The Transcription Factor Hand1 Is Involved In Runx2-Ihh-Regulated Endochondral Ossification. |
| ジャーナル | PLoS One |
| Abstract |
The developing long bone is a model of endochondral ossification that displays the morphological layers of chondrocytes toward the ossification center of the diaphysis. Indian hedgehog (Ihh), a member of the hedgehog family of secreted molecules, regulates chondrocyte proliferation and differentiation, as well as osteoblast differentiation, through the process of endochondral ossification. Here, we report that the basic helix-loop-helix transcription factor Hand1, which is expressed in the cartilage primordia, is involved in proper osteogenesis of the bone collar via its control of Ihh production. Genetic overexpression of Hand1 in the osteochondral progenitors resulted in prenatal hypoplastic or aplastic ossification in the diaphyses, mimicking an Ihh loss-of-function phenotype. Ihh expression was downregulated in femur epiphyses of Hand1-overexpressing mice. We also confirmed that Hand1 downregulated Ihh gene expression in vitro by inhibiting Runx2 transactivation of the Ihh proximal promoter. These results demonstrate that Hand1 in chondrocytes regulates endochondral ossification, at least in part through the Runx2-Ihh axis. |
| 巻・号 | 11(2) |
| ページ | e0150263 |
| 公開日 | 2016-1-1 |
| DOI | 10.1371/journal.pone.0150263 |
| PII | PONE-D-16-01770 |
| PMID | 26918743 |
| PMC | PMC4769249 |
| MeSH | Animals Basic Helix-Loop-Helix Transcription Factors / genetics Basic Helix-Loop-Helix Transcription Factors / physiology* Bone and Bones / embryology Bone and Bones / metabolism Bone and Bones / pathology Cell Line Core Binding Factor Alpha 1 Subunit / antagonists & inhibitors* Core Binding Factor Alpha 1 Subunit / physiology Diaphyses Down-Regulation Female Genes, Reporter Growth Plate / metabolism Hedgehog Proteins / biosynthesis Hedgehog Proteins / deficiency Hedgehog Proteins / genetics Hedgehog Proteins / physiology* Limb Deformities, Congenital / genetics Male Mice Mice, Transgenic Osteogenesis / genetics Osteogenesis / physiology* Osteopontin / biosynthesis Osteopontin / genetics Phenotype Promoter Regions, Genetic / genetics Real-Time Polymerase Chain Reaction Recombinant Fusion Proteins / metabolism Repressor Proteins / genetics Signal Transduction / physiology Transcriptional Activation* Transfection Twist-Related Protein 1 / genetics |
| IF | 2.74 |
| リソース情報 | |
| ヒト・動物細胞 | ATDC5(RCB0565) COS-1(RCB0143) |