Development of molecular-targeted therapies for pain control on inhibiting porosity of the vertebral endplate and bone loss

2022 Fiscal Year Final Research Report

• Project/Area Number: 21K16679
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 56020:Orthopedics-related
• Research Institution: University of Toyama
• Principal Investigator: Makino Hiroto 富山大学, 附属病院, 助教 (50816022)
• Project Period (FY): 2021-04-01 – 2023-03-31
• Keywords: 椎間板 / 椎体終板 / c-Fos

Outline of Final Research Achievements

In this study, we have focused on bone defects of the vertebral endplate and its pathogenesis and controlled its molecular mechanism so that inhibiting spinal degenerative changes and pain. CT imaging analysis revealed the defects in the endplate of patients with lumbar disc disease. We confirmed the effect of selective c-Fos/AP-1 inhibitors on osteoclast differentiation, which have the effect of ameliorating the imbalance in extracellular matrix metabolism in the intervertebral disc. It was found that the differentiation of mouse bone marrow-derived stem cells into osteoclasts was inhibited by the addition of selective c-Fos/AP-1 inhibitors. The results suggest that selective c-Fos/AP-1 inhibition may be useful in suppressing the bone defects of the endplate.

Free Research Field

椎間板代謝

Academic Significance and Societal Importance of the Research Achievements

これまでに椎間板変性ならびに椎間板に関連する疼痛抑制効果および骨量増加効果を併せ持つ薬剤はなく、本研究でそれを示すことができれば、臨床応用も考慮されうる。脊椎退行性疾患患者における骨粗鬆症の合併例は稀ではなく、手術に至らない患者において、疼痛の軽減と骨量増加を期待できる治療法として確立することができれば、社会的利益は大きい。