The Transcription Factor Hand1 Is Involved In Runx2-Ihh-Regulated Endochondral Ossification

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 differentiati...

Ausführliche Beschreibung

Gespeichert in:
Bibliographische Detailangaben
Veröffentlicht in:PloS one 2016-02, Vol.11 (2), p.e0150263-e0150263
Hauptverfasser: Laurie, Lindsay E, Kokubo, Hiroki, Nakamura, Masataka, Saga, Yumiko, Funato, Noriko
Format: Artikel
Sprache:eng
Schlagworte:
DNA
Online-Zugang:Volltext
Tags: Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
Beschreibung
Zusammenfassung: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.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0150263