| Project/Area Number |
18K09066
|
|---|
| 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 | Hiroshima University |
|---|
Principal Investigator |
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
安達 伸生 広島大学, 医系科学研究科(医), 教授 (30294383)
味八木 茂 広島大学, 病院(医), 講師 (10392490)
石川 正和 広島大学, 医系科学研究科(医), 寄附講座准教授 (60372158)
|
|---|
| Project Period (FY) |
2018-04-01 – 2021-03-31
|
| Project Status |
Completed (Fiscal Year 2020)
|
| Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
|
|---|
| Keywords | 変形性関節症（OA） / 神経ペプチド / 変形性関節症 / microRNA |
|---|
| Outline of Final Research Achievements |
In the OA pathogenesis, cartilage degeneration due to the subchondral bone sclerosis and degenerations of the tissues such as menisci and ligament occur. Identification of factors which causes these changes will lead to develop new treatment. We focused on neuropeptides which have various functions such as bone metabolism and angiogenesis as well as pain. We showed that neuropeptides are involved in the OA pathogenesis. The expression patterns of the calcitonin gene-related peptide (CGRP)、vasoactive intestinal peptide (VIP)、substance P were examined in human OA and OA model mice. The expression of these neuropeptides increased with the sclerotic changes of the subchondral bone. Interaperitoneal administration of CGRP, VIP receptor antagonist, and substance P agonist to OA model mice could suppress the OA progression. In addition, RNA sequence of microRNA using OA model mice serum revealed some expression patterns during OA progression.
|
| Academic Significance and Societal Importance of the Research Achievements |
これまでのOAの病態における研究は、関節軟骨や炎症性サイトカイン、軟骨基質分解酵素等に関するものが多かった。またOAにおける神経ペプチドの研究も散見されるが、これらは疼痛に関するものであった。本研究では、神経ペプチドが疼痛だけではなく、骨代謝や炎症、血管新生等にも関わっており、治療標的となる可能性が示唆できた。現状では、OAの進行を遅らせる薬剤はない。神経ペプチド受容体拮抗薬は、偏頭痛の治療薬等で実際に臨床において使用できるものもあり、drug repositioningにより、新たなOAの治療薬に発展するものと思われる。
|
