| First Author | Han X | Year | 2013 |
| Journal | Cell Signal | Volume | 25 |
| Issue | 11 | Pages | 2136-46 |
| PubMed ID | 23816533 | Mgi Jnum | J:316967 |
| Mgi Id | MGI:6843261 | Doi | 10.1016/j.cellsig.2013.06.011 |
| Citation | Han X, et al. (2013) IRE1alpha dissociates with BiP and inhibits ER stress-mediated apoptosis in cartilage development. Cell Signal 25(11):2136-46 |
| abstractText | Bone morphogenetic protein 2 is known to activate unfolded protein response signaling molecules, including XBP1S, BiP and IRE1alpha. Endoplasmic reticulum stress is induced in chondrogenesis and activates IRE1alpha signal pathway, which is associated with ER stress-mediated apoptosis. However, the influence on IRE1alpha and BiP in BMP2-induced chondrocyte differentiation has not yet been elucidated; the molecular mechanism remains unexplored. In this study, we demonstrate that IRE1alpha interacts with BiP in unstressed cells and dissociates from BiP in the course of cartilage development. Induction of ER stress-responsive proteins (XBP1S, IRE1alpha, BiP) was also observed in differentiating cells. IRE1alpha inhibition ER stress-mediated apoptosis lies in the process of chondrocyte differentiation. Furthermore, knockdown of IRE1alpha 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 IRE1alpha 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 IRE1alpha 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. |
