Authors: Naoko Hatakeyama Takashi Kojima Kousuke Iba Masaki Murata Mia M Thi David C Spray Makoto Osanai Hideki Chiba Sumio Ishiai Toshihiko Yamashita Norimasa Sawada
Publish Date: 2008/10/15
Volume: 334, Issue: 2, Pages: 243-
Abstract
Insulinlike growth factor I IGFI is expressed in many tissues including bone and acts on the proliferation and differentiation of osteoblasts as an autocrine/paracrine regulator Tightjunction proteins have been detected in osteoblasts and direct celltocell interactions may modulate osteoblast function with respect for example to gap junctions In order to investigate the regulation of expression of tightjunction molecules and of function during bone differentiation osteoblastlike MC3T3E1 cells and osteocytelike MLOY4 cells were treated with IGFI In both MC3T3E1 cells and MLOY4 cells the tightjunction molecules occludin claudin1 2 and 6 and the gapjunction molecule connexin 43 Cx43 were detected by reverse transcription with polymerase chain reaction In MC3T3E1 cells but not MLOY4 cells mRNAs of claudin1 2 and 6 Cx43 and type I collagen and proteins of claudin1 and Cx43 were increased after treatment with IGFI Such treatment significantly decreased paracellular permeability in MC3T3E1 cells The expression of claudin1 in MC3T3E1 cells after IGFI treatment was mainly upregulated via a mitogenactivated protein MAPkinase pathway and in part modulated by a PI3kinase pathway whereas Cx43 expression and the mediated gapjunctional intercellular communication protein did not contribute to the upregulation Furthermore in MC3T3E1 cells during wound healing upregulation of claudin1 was observed together with an increase of IGFI and type I collagen These findings suggest that the induction of tightjunction protein claudin1 and paracellular permeability during the differentiation of osteoblastlike MC3T3E1 cells after treatment with IGFI is regulated via a MAPkinase pathway but not with respect to gap junctionsThis work was supported by GrantsinAid from the National Project “Knowledge Cluster Initiative” 2nd stage “Sapporo Biocluster Bios” the Ministry of Education Culture Sports Science and Technology and the Ministry of Health Labor and Welfare of Japan the Akiyama Foundation and the Japan Science and Technology Agency
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