Novel treatment strategy based on molecular mechanisms of various diseases causing low back pain

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K09613
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 56020:Orthopedics-related
• Research Institution: National Defense Medical College
• Principal Investigator: Chiba Kazuhiro 防衛医科大学校(医学教育部医学科進学課程及び専門課程、動物実験施設、共同利用研究施設、病院並びに防衛, 病院 整形外科, 教授 (80179952)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: 腰痛 / 椎間板 / 椎間板変性 / 動物モデル / 脊椎腫瘍 / 骨肉腫 / 滑膜肉腫

Outline of Final Research Achievements

We attempt to establish rat model of intervertebral disc degeneration by needle puncture, radiation, and enzyme injection. Injection of condoliase produced changes most similar to human disc degeneration. Using this model, we are testing feasibility of various drugs and cytokines to slow down or possibly reverse disc degeneration, thereby establishing new treatment strategy for degenerative disc diseases. We found that trabectedin significantly suppressed pulmonary metastasis in mouse osteosarcoma model by inhibiting cell migration potentially through down-regulating ERK1/2, intracellular molecules that are critically involved in cell motility regulation. We also found that eribulin exhibited potent antitumor activity against synovial sarcoma by inducing intussusceptive angiogenesis, distinct form of angiogenesis potentially involved in vascular remodeling, thereby improving intratumoral hypoxia. These finding may lead to establishment of new treatment strategy against spinal tumors.

Free Research Field

脊椎脊髄外科学

Academic Significance and Societal Importance of the Research Achievements

本研究は、椎間板細胞の変性機序そのものに注目してその分子遺伝学的メカニズムを解明し、その知見から特に重要な形質や因子を同定し、機能破綻を来す以前に椎間板変性過程そのものを遅延あるいは停止あわよくば逆行させるという、全く新たな発想に基づくより低侵襲かつ経済的な治療戦略確立の可能性を模索する独創的なものであり、患者のQOLの向上は勿論、医療経済上も大きな恩恵をもたらすものと期待される。また、脊椎腫瘍に関しては、悪性骨軟部腫瘍に対する新規薬剤の抗腫瘍作用を詳細に検討することで、新たな分子メカニズムを解明し、副作用が少なくより有効な新規治療法の開発に繋がるものと期待される。