The Transcription Factor EB (TFEB) Regulates Osteoblast Differentiation Through ATF4/CHOP-Dependent Pathway

Erika Yoneshima, Kuniaki Okamoto, Eiko Sakai, Kazuhisa Nishishita, Noriaki Yoshida, Takayuki Tsukuba

Research output: Contribution to journalArticle

10 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)1321-1333
Number of pages13
JournalJournal of Cellular Physiology
Volume231
Issue number6
DOIs
Publication statusPublished - Jun 1 2016
Externally publishedYes

Fingerprint

Activating Transcription Factor 4
Transcription Factor CHOP
Osteoblasts
Transcription Factors
Bone
CCAAT-Enhancer-Binding Proteins
Gene Knockdown Techniques
Bone Matrix
Collagen Type I
Lysosomes
Small Interfering RNA
Proteins
Up-Regulation
Genes
Bone and Bones

ASJC Scopus subject areas

  • Clinical Biochemistry
  • Cell Biology
  • Physiology
  • Medicine(all)

Cite this

The Transcription Factor EB (TFEB) Regulates Osteoblast Differentiation Through ATF4/CHOP-Dependent Pathway. / Yoneshima, Erika; Okamoto, Kuniaki; Sakai, Eiko; Nishishita, Kazuhisa; Yoshida, Noriaki; Tsukuba, Takayuki.

In: Journal of Cellular Physiology, Vol. 231, No. 6, 01.06.2016, p. 1321-1333.

Research output: Contribution to journalArticle

Yoneshima, Erika ; Okamoto, Kuniaki ; Sakai, Eiko ; Nishishita, Kazuhisa ; Yoshida, Noriaki ; Tsukuba, Takayuki. / The Transcription Factor EB (TFEB) Regulates Osteoblast Differentiation Through ATF4/CHOP-Dependent Pathway. In: Journal of Cellular Physiology. 2016 ; Vol. 231, No. 6. pp. 1321-1333.
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