The approach of molecular treatments for the intervertebral disc degeneration.

2017 Fiscal Year Final Research Report

• Project/Area Number: 15K10406
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Orthopaedic surgery
• Research Institution: Kobe University
• Principal Investigator: Maeno Koichiro 神戸大学, 医学研究科, 医学研究員 (70403269)
• Co-Investigator(Kenkyū-buntansha): 西田 康太郎 神戸大学, 医学研究科, 准教授 (00379372) ; 由留部 崇 神戸大学, 医学部附属病院, その他 (10514648) ; 角谷 賢一朗 神戸大学, 医学研究科, 助教 (10533739)
• Research Collaborator: Miyazaki Shingo 神戸大学, 大学院医学研究科, 大学院生 ; Terashima Yoshiki 神戸大学, 大学院医学研究科, 大学院生 ; Ito Masaaki 神戸大学, 大学院医学研究科, 大学院生 ; Takeoka Yoshiki 神戸大学, 大学院医学研究科, 大学院生 ; Kakiuti Yuji 神戸大学, 大学院医学研究科, 大学院生
• Project Period (FY): 2015-04-01 – 2018-03-31
• Keywords: 椎間板 / mTOR / Raptor / siRNA / アポトーシス / オートファジー / セネッセンス / mTORC1阻害薬

Outline of Final Research Achievements

mTORC1 suppression through RNAi for Raptor showed protective effects against human NP cell apoptosis, senescence, and matrix degradation. This study suggests that selective inhibition for mTORC1 but not mTORC2 is beneficial to human NP cells, which depends on Akt as well as autophagy induction. Thus, Raptor is a potent target for new molecular treatments for human degenerative disc disease. And also, in our results, the first generation mTOR inhibitors suppressed mTOR signaling, induced autophagy and Akt, and showed protective effects against human disc NP cell apoptosis and senescence. In clinical use, adverse immunosuppression of mTOR inhibitors would recommend its local intra-discal injection rather than its systemic administration. To accomplish successful local delivery of agents, water solubility is a key factor. Therefore, intra-discal injection of temsirolimus that has improved water solubility is a potential therapeutic application to human degenerative disc disease.

Free Research Field

整形外科