Development of treatment strategies for intervertebral disc degeneration by modulating autophagy

2015 Fiscal Year Final Research Report

• Project/Area Number: 26893151
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Single-year Grants
• Research Field: Orthopaedic surgery
• Research Institution: Kobe University
• Principal Investigator: YURUBE Takashi 神戸大学, 医学部附属病院, その他 (10514648)
• Project Period (FY): 2014-08-29 – 2016-03-31
• Keywords: 椎間板変性 / オートファジー / 老化 / 脊椎 / 整形外科

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.

Free Research Field

整形外科