| Budget Amount *help |
¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
Fiscal Year 2014: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2013: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2012: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
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| Outline of Final Research Achievements |
Endoplasmic reticulum (ER) stress transducer, BBF2H7, is cleaved in response to ER stress and the N-terminus acts as a transcription factor during chondrogenesis. The activated BBF2H7 promotes cartilage matrix protein secretion through the up-regulation of Sec23a, which is a target of BBF2H7. We elucidated the mechanisms of transcriptional activation of BBF2H7 in chondrocytes. Transcription of BBF2H7 is directly regulated by Sox9, a critical factor for chondrocyte differentiation that facilitates the expression of Type II collagen (Col2). Our findings demonstrate novel mechanisms of Sox9 for controlling the secretion of cartilage matrix proteins via activation of BBF2H7-Sec23a. Furthor, we demonstrated that the cleaved C-terminus is secreted to extracellular space and promotes chondrocyte proliferation via the activation of hedgehog signaling. In addition, we found that BBF2H7 activates ATF5-MCL1 pathway to avoid apoptosis during chondrogenesis.
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