RRC ID 38876
著者 Yoneshima E, Okamoto K, Sakai E, Nishishita K, Yoshida N, Tsukuba T.
タイトル The Transcription Factor EB (TFEB) Regulates Osteoblast Differentiation Through ATF4/CHOP-Dependent Pathway.
ジャーナル J Cell Physiol
Abstract Osteoblasts are bone-forming cells that produce large amounts of collagen type I and various bone matrix proteins. Although osteoblast differentiation is highly regulated by various factors, it remains unknown whether lysosomes are directly involved in osteoblast differentiation. Here, we demonstrate the transcription factor EB (TFEB), a master regulator of lysosomal biogenesis, modulates osteoblast differentiation. The expression levels of TFEB as well as those of endosomal/lysosomal proteins were up-regulated during osteoblast differentiation using mouse osteoblastic MC3T3-E1 cells. By gene knockdown (KD) experiments with small interfering RNA (siRNA), TFEB depletion caused markedly reduced osteoblast differentiation as compared with the control cells. Conversely, overexpression (OE) of TFEB resulted in strikingly enhanced osteoblastogenesis compared to the control cells. By analysis of down-stream effector molecules, TFEB KD was found to cause marked up-regulation of activating transcription factor 4 (ATF4) and CCAAT/enhancer-binding protein homologous protein (CHOP), both of which are essential factors for osteoblastogenesis. In contrast, TFEB OE promoted osteoblast differentiation through reduced expression of ATF4 and CHOP without differentiation agents. Given the importance of ATF4 and CHOP in osteoblastogenesis, it is clear that the TFEB-regulated signaling pathway for osteoblast differentiation is involved in ATF4/CHOP-dependent signaling pathway.
巻・号 231(6)
ページ 1321-33
公開日 2016-6-1
DOI 10.1002/jcp.25235
PMID 26519689
MeSH 3T3 Cells Activating Transcription Factor 4 / genetics Activating Transcription Factor 4 / metabolism* Animals Apoptosis Basic Helix-Loop-Helix Leucine Zipper Transcription Factors / genetics Basic Helix-Loop-Helix Leucine Zipper Transcription Factors / metabolism* Bone Morphogenetic Protein 2 / pharmacology Cell Differentiation* / drug effects Endosomes / metabolism Gene Expression Regulation Gene Knockdown Techniques Lysosomes / metabolism Mice Mitochondria / metabolism Osteoblasts / drug effects Osteoblasts / metabolism* Osteoblasts / pathology RNA Interference Reactive Oxygen Species / metabolism Signal Transduction* / drug effects Smad1 Protein / genetics Smad1 Protein / metabolism Smad5 Protein / genetics Smad5 Protein / metabolism Transcription Factor CHOP / genetics Transcription Factor CHOP / metabolism* Transfection
IF 5.546
引用数 15
WOS 分野 PHYSIOLOGY CELL BIOLOGY
リソース情報
ヒト・動物細胞 MC3T3-E1(RCB1126)