RETRACTED ARTICLE: Explore on the effect of ATF6 on cell growth and apoptosis in cartilage development
Authors: Feng-Jin Guo
Xiaofeng Han
Fei Xia
Peng Zhang
Rong Jiang
Meiling Li
Journal: Histochemistry and cell biology (2014)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: BMP2; ER stress; ATF6; XBP1S splicing; chondrogenesis
Affiliations: Department of Cell Biology and Genetics, Core Facility of Development Biology, Chongqing Medical University, Chongqing, 400016, China.

Abstract:  We previously report that BMP2 mediates mild ER stress-activated ATF6 and directly regulates XBP1S splicing in the course of chondrogenesis. The mammalian unfolded protein response (UPR) protects the cell against the stress of misfolded proteins in the endoplasmic reticulum (ER). Failure to adapt to ER stress causes the UPR to trigger apoptosis. The transcription factor activating transcription factor 6 (ATF6), a key regulator of the UPR, is known to be important for ER stress-mediated apoptosis and cell growth, but the molecular mechanism underlying these processes remains unexplored. In this study, we demonstrate that ATF6 is differentially expressed during BMP2-stimulated chondrocyte differentiation and exhibits prominent expression in growth plate chondrocytes. ATF6 can enhance the level of IRE1a-spliced XBP1S protein in chondrogenesis. IRE1a and ATF6 can synergistically regulate endogenous XBP1S gene expression in chondrogenesis. Furthermore, overexpression ATF6 inhibited, while ATF6-knockdown enhanced, the cell proliferation in chondrocyte development with G1 phase arresting, S phase reducing and G2-M phase delaying. Besides, Ad-ATF6 can activate, whereas knockdown ATF6 by an siRNA-silencing approach inhibited, ER stress-mediated apoptosis in chondrogenesis induced by BMP2, as assayed by cleaved caspase3, CHOP, p-JNK expression in the course of chondrocyte differentiation. On the other hand, FCM, TUNEL assay and immunohistochemistry analysis also proved this result in vitro and in vivo. It was demonstrated that Ad-ATF6 activation of the ER stress-specific caspase cascade in developing chondrocyte tissue. Collectively, these findings reveal a novel critical role of ATF6 in regulating ER stress-mediated apoptosis in chondrocyte differentiation and the molecular mechanisms involved. 

Retracted: Yes

PubPeer comments:
 Explore on the effect of ATF6 on cell growth and apoptosis in cartilage development. Han X, Zhang P, Jiang R, Xia F, Li M, Guo FJ. Histochem Cell Biol. **2014** Nov;142(5):497-509. doi: 10.1007 s00418-014-1233-y. Epub 2014 Jun 17. PMID: 24934104 XBP1S associates with RUNX2 and regulates chondrocyte hypertrophy. Liu Y, Zhou J, Zhao W, Li X, Jiang R, Liu C, Guo FJ. J Biol Chem. **2012** Oct 5;287(41):34500-13. doi: 10.1074 jbc.M112.385922. Epub 2012 Aug 3. Retraction in: J Biol Chem. 2015 Apr 24;290(17):10643. PMID: 22865880 ![file] , 
 Does Pubpeer usually notify the journal editor for every questionable paper? As you can find that this paper has been published for more than 5 years and has got 14 citations. No expression of concern has been posted on the journal website. Is there anything we can do? ![file] , 
 The Editor-in-Chief has retracted the article by Han et al. (2014) because Fig. 3a-d are also published as Fig. 5b-e in Liu et al. (2012), and Fig. 3a, c, d are also published as Fig. 5a, d, e in Guo et al. (2014). ,