title: IGF1 promotes osteogenic differentiation of mesenchymal stem cells derived from rat bone marrow by increasing TAZ expression.
abstract: Whether insulin-like growth factor 1 (IGF1) inhibits or promotes the osteogenic differentiation in vitro remains controversial. Moreover, the biological mechanisms and signaling pathways by which IGF1 affects osteogenic differentiation remain obscure. Transcriptional coactivator with PDZ-binding motif (TAZ) plays a vital role in the osteogenic differentiation of mesenchymal stem cells (MSCs), and strongly activates runt related transcription factor 2 (RUNX2)-driven genes during the terminal osteogenic differentiation. In the present study, we found that IGF1 increased the ALP activities and calcium depositions of MSCs derived from rat bone marrow dose-dependently, with a peak at 100-200ng/ml. IGF1 increased TAZ and RUNX2 expression mainly at the early stage of osteogenic differentiation, but increased OCN expression at the late stage. Our data further demonstrated that down-regulation of TAZ expression by siRNA inhibited the IGF1 induced increase in osteogenic differentiation. Moreover, UO126 (the MEK-ERK inhibitor), not LY294002 (the PI3K-Akt inhibitor), inhibited the IGF1 induced increase in TAZ expression. Taken together, we provide evidence to demonstrate that IGF1 promotes the osteogenic differentiation of rat MSCs by increasing TAZ expression, and that the increased TAZ expression induced by IGF1 is mostly mediated by the MEK-ERK pathway.
authors.affiliation: Department of Endocrinology, The Third Hospital of Hebei Medical University, 139 Ziqiang Road, Shijiazhuang, Hebei Province 050000, PR China.
authors.forename: Peng
authors.initials: P
authors.lastname: Xue
authors.forename: Xuelun
authors.initials: X
authors.lastname: Wu
authors.forename: Lixin
authors.initials: L
authors.lastname: Zhou
authors.forename: Huan
authors.initials: H
authors.lastname: Ma
authors.forename: Yan
authors.initials: Y
authors.lastname: Wang
authors.forename: Yan
authors.initials: Y
authors.lastname: Liu
authors.forename: Jianxia
authors.initials: J
authors.lastname: Ma
authors.forename: Yukun
authors.initials: Y
authors.lastname: Li
mesh_terms: D000217:Acyltransferases; D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology; D002070:Butadienes / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology*; D002867:Chromones / Q000494:pharmacology; D050659:Core Binding Factor Alpha 1 Subunit / Q000235:genetics / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005786:Gene Expression Regulation / Q000187:drug effects; D007334:Insulin-Like Growth Factor I / Q000378:metabolism / Q000494:pharmacology*; D020935:MAP Kinase Signaling System / Q000187:drug effects; D008297:Male; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000187:drug effects; D009025:Morpholines / Q000494:pharmacology; D009570:Nitriles / Q000494:pharmacology; D015675:Osteocalcin / Q000235:genetics / Q000378:metabolism; D010012:Osteogenesis / Q000502:physiology; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D000081082:Phosphoinositide-3 Kinase Inhibitors; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D034741:RNA, Small Interfering; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism
chemical_list: D000217:Acyltransferases; D002070:Butadienes; D002118:Calcium; D002867:Chromones; D050659:Core Binding Factor Alpha 1 Subunit; D007334:Insulin-Like Growth Factor I; D009025:Morpholines; D009570:Nitriles; D015675:Osteocalcin; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D051057:Proto-Oncogene Proteins c-akt; D034741:RNA, Small Interfering; D014157:Transcription Factors; C493717:Runx2 protein, rat; C113580:U 0126; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; C544439:Tafazzin protein, rat