Osteoblastogenic effects of dexamethasone through upregulation of TAZ expression in rat mesenchymal stem cells.
Transcriptional coactivator with PDZ-binding motif (TAZ), a beta-catenin-like molecule, drives mesenchymal stem cell (MSC) to differentiate into osteoblast lineage through co-activation of Runx2-dependent gene transcription and repression of peroxisome proliferator-activated receptorgamma (PPARgamma)-dependent gene transcription. Dexamethasone (DEX), a synthetic and widely used glucocorticoid, affects osteogenesis. However, the signaling pathway by which DEX affects osteoblastic differentiation remains obscure. In this study, we found that DEX at the concentration of 10(-8)M enhanced calcium deposition, TAZ, bone morphogenetic protein 2 (BMP-2) and alkaline phosphatase (ALP) expression during osteoblastic differentiation. RU486, an antagonist of glucocorticoid receptor, blocked the improvement of TAZ expression while MSCs were treated with 10(-8)M DEX. Moreover, higher concentration (10(-7)M) of DEX robustly suppressed TAZ and ALP expression in MSCs. These findings suggest that TAZ is not only involved in the signal pathway of BMP-2-induced osteoblastic differentiation, but also involved in the signaling pathway of DEX-induced osteoblastic differentiation, supporting the notion that TAZ is a convergence point of two signaling pathways, BMP-2 signaling pathway and Wnt-beta-catenin signaling pathway.
Hong
Dun
D
Institute of Cell Biology, Medical College of Zhejiang University, 388 Yuhangtang Road, Hangzhou 310058, Zhejiang Province, China.
Chen
Hai-Xiao
HX
Xue
Yun
Y
Li
Dong-Mei
DM
Wan
Xiao-Chen
XC
Ge
Renshan
R
Li
Ji-Cheng
JC
D000217:Acyltransferases; D000469:Alkaline Phosphatase / Q000235:genetics / Q000378:metabolism; D000818:Animals; D000954:Antigens, Surface / Q000378:metabolism; D055396:Bone Morphogenetic Protein 2 / Q000235:genetics / Q000378:metabolism; D002454:Cell Differentiation; D050659:Core Binding Factor Alpha 1 Subunit / Q000235:genetics / Q000378:metabolism; D003907:Dexamethasone / Q000494:pharmacology*; D005938:Glucocorticoids / Q000494:pharmacology*; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D010006:Osteoblasts / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D010012:Osteogenesis; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism; D015854:Up-Regulation; D051153:Wnt Proteins / Q000235:genetics / Q000378:metabolism
D000954:Antigens, Surface; D055396:Bone Morphogenetic Protein 2; D050659:Core Binding Factor Alpha 1 Subunit; D005938:Glucocorticoids; D012333:RNA, Messenger; D014157:Transcription Factors; D051153:Wnt Proteins; D003907:Dexamethasone; D000217:Acyltransferases; C544439:Tafazzin protein, rat; D000469:Alkaline Phosphatase