期刊
CELLULAR SIGNALLING
卷 25, 期 11, 页码 2136-2146出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.cellsig.2013.06.011
关键词
Endoplasmic reticulum stress; Apoptosis; UPR; IRE1 alpha; BiP; Cartilage development
类别
资金
- National Science Foundation of China [81171697]
- New Century Excellent Talent Support Project of Education Ministry of China [NCET-12-1090]
- Returned Overseas Preferred Funded Project of Human Resources and Social Security Ministry of China [2011-235]
- University Excellent Talent Support Project of CQEC [2011-65]
Bone morphogenetic protein 2 is known to activate unfolded protein response signaling molecules, including XBP1S, BiP and IRE1 alpha. Endoplasmic reticulum stress is induced in chondrogenesis and activates IREl alpha signal pathway, which is associated with ER stress-mediated apoptosis. However, the influence on IRE1 alpha and BiP in BMP2-induced chondrocyte differentiation has not yet been elucidated; the molecular mechanism remains unexplored. In this study, we demonstrate that IRE1 alpha interacts with BiP in unstressed cells and dissociates from BiP in the course of cartilage development. Induction of ER stress-responsive proteins (XBP1S, IRE1 alpha, BiP) was also observed in differentiating cells. IRE1 alpha inhibition ER stress-mediated apoptosis lies in the process of chondrocyte differentiation. Furthermore, knockdown of IRE1 alpha expression by way of the RNAi approach accelerates ER stress-mediated apoptosis in chondrocyte differentiation induced by BMP2, as revealed by enhanced expressions of cleaved caspase3, CHOP and p-JNK1; and this IRE1 alpha inhibition effect on ER stress-mediated apoptosis is required for BiP in chondrogenesis. Collectively, the ER stress sensors were activated during apoptosis in cartilage development, suggesting that selective activation of ER stress signaling was sufficient for induction of apoptosis. These findings reveal a novel critical role of IRE1 alpha in ER stress-mediated apoptosis and the molecular mechanisms involved. These results suggest that activation of p-JNK1, caspase3 and CHOP was detected in developing chondrocytes and that specific ER stress signaling leads to naturally occurring apoptosis during cartilage development. Crown Copyright (C) 2013 Published by Elsevier Inc. All rights reserved.
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