In vivo expression and regulation of genes associa

Authors: Nobuo Takeshita Masakazu Hasegawa Kiyo Sasaki Daisuke Seki Masahiro Seiryu Shunro Miyashita Ikuko Takano Toshihito Oyanagi Yuki Miyajima Teruko TakanoYamamoto

Publish Date: 2016/01/29

Volume: 35, Issue: 1, Pages: 40-51

PDF Link

Abstract

Sutures are fibrous tissues that connect bones in craniofacial skeletal complexes Cranio and dentofacial skeletal deformities in infant and adolescent patients can be treated by applying tensile force to sutures to induce sutural bone formation The early gene expression induced by mechanical stress is essential for bone formation in long bones however early gene expression during sutural bone formation induced by tensile force is poorly characterized In vivo studies are essential to evaluate molecular responses to mechanical stresses in heterogeneous cell populations such as sutures In this paper we examined in vivo early gene expression and the underlying regulatory mechanism for this expression in tensileforceapplied cranial sutures focusing on genes involved in vascularization Tensile force upregulated expression of vascular factors such as vascular endothelial growth factor Vegf and endothelial cell markers in sutures within 3 h The expression of connective tissue growth factor Ctgf and Rhoassociated coiledcoil containing protein kinase 2 Rock2 was also upregulated by tensile force A CTGFneutralizing antibody and the ROCK inhibitor Y27632 abolished tensileforceinduced Vegf expression Moreover tensile force activated extracellular signalrelated kinase 1/2 ERK1/2 signaling in sagittal sutures and the ERK1/2 inhibitor U0126 partially inhibited tensileforceinduced Ctgf expression These results indicate that tensile force induces in vivo gene expression associated with vascularization early in tensileforceinduced sutural bone formation Moreover the early induction of Vegf gene expression is regulated by CTGF and ROCK2The authors thank Dr H Kitaura Tohoku University Graduate School of Dentistry for his valuable technical instructions This work was supported by a GrantinAid for Scientific Research A and B to TTY a GrantinAid for Scientific Research C to NT from the Japan Society for the Promotion of Science and in part by a grant to TTY from the Japan Society and Technology Agency

Keywords: