| Budget Amount *help |
¥2,990,000 (Direct Cost: ¥2,300,000、Indirect Cost: ¥690,000)
Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2014: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
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| Outline of Final Research Achievements |
This study aimed the elucidation of roles of autophagy in intervertebral disc degeneration, providing insight into potential therapeutic targets. In our study, pharmacological induction of autophagy using rapamycin, an mTORC1 inhibitor, had protective effects against disc cellular apoptosis, senescence, and extracellular matrix degradation. In addition, we found that partial inhibition of mTORC1 only, but not of Akt and mTORC2 which exist in the upstream of mTORC1, provides these beneficial effects on disc cells. Furthermore, discs of rapamycin-fed mice demonstrated decreased degradation of aggrecan, a major matrix molecules, by both of MMPs and ADAMTSs. These findings suggest modulation of autophagy and related mTOR signaling as a possible treatment strategy for degenerative disc disease.
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