Development of molecular-targeted therapies for pain control on inhibiting porosity of the vertebral endplate and bone loss
| Project/Area Number |
21K16679
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| Research Category |
Grant-in-Aid for Early-Career Scientists
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| Allocation Type | Multi-year Fund |
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| Review Section |
Basic Section 56020:Orthopedics-related
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| Research Institution | University of Toyama |
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Principal Investigator |
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| Project Period (FY) |
2021-04-01 – 2023-03-31
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| Project Status |
Completed (Fiscal Year 2022)
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| Budget Amount *help |
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2022: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2021: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
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| Keywords | 椎間板 / 椎体終板 / c-Fos / 骨性欠損 / 脊椎 / 破骨細胞 |
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| Outline of Research at the Start |
脊椎は主に椎間板と椎体によって構成される。椎間板の退行性変化は腰痛症や脊柱管狭窄症を、椎体の老化は骨粗鬆症性椎体骨折を引き起こす。しかし、椎間板と椎体の機能を同時に改善し得る治療法は未だ存在しない。我々は、T-5224が細胞外マトリックス代謝不均衡による椎間板変性と疼痛を抑制することを明らかにした。さらに近年、椎体終板に存在する破骨細胞の活性化が、疼痛を惹起する可能性が報告された。転写因子c-Fosは、破骨細胞の分化に必須である。本研究では、T-5224の椎体終板の多孔化抑制効果、骨量減少抑制効果、疼痛抑制効果を明らかにし、椎間板と椎体の機能を同時に改善し得る新規分子標的治療法の創出を目指す。
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| 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.
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| 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。
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Report
(3 results)
Research Products
(7 results)
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[Journal Article] Association of Ligamentum Flavum Hypertrophy with Adolescent Idiopathic Scoliosis Progression-Comparative Microarray Gene Expression Analysis2022
Author(s)
Seki S, Iwasaki M, Makino H, Yahara Y, Kondo M, Kamei K, Futakawa H, Nogami M, Watanabe K, Tran Canh Tung N, Hirokawa T, Tsuji M, Kawaguchi Y.
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Journal Title
Int J Mol Sci .
Volume: 23
Issue: 9
Pages: 5038-5038
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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