Study on the role of proteoglycans of mast cells and macrophages in the control of inflammation and pain
| Project/Area Number |
16K08999
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Multi-year Fund |
|---|
| Section | 一般 |
|---|
| Research Field |
Pain science
|
|---|
| Research Institution | Aichi Medical University |
|---|
Principal Investigator |
Habuchi Osami 愛知医科大学, 公私立大学の部局等, 客員教授 (90024067)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
羽渕 弘子 愛知医科大学, 公私立大学の部局等, 客員研究員 (90329821)
|
|---|
| Project Period (FY) |
2016-04-01 – 2020-03-31
|
| Project Status |
Completed (Fiscal Year 2019)
|
| Budget Amount *help |
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2018: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2016: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
|
|---|
| Keywords | 変形性関節炎 / モノヨード酢酸 / 肥満細胞 / 痛み / トリプターゼ / PAR2 / ATP / アピラーゼ / 骨髄由来肥満細胞 / P2X7、P2X4 / 膝関節炎 / Fat pad / 疼痛 / 高硫酸化プロテオグリカン / マクロファージ / プロテオグリカン |
|---|
| Outline of Final Research Achievements |
We found that bone marrow derived mast cells (BMMCs) elicited pain when injected into monoiodoacetic acid (MIA)-induced osteoarthritic mouse knee joint. No pain induction was observed when BMMCs were injected into the MIA-untreated mice, indicating that the injected BMMCs are thought to be activated within the osteoarthritic joint and release some pain-inducible factors. When BMMCs were injected in the presence of a protease activated receptor-2 (PAR2) antagonist peptide, they failed to induce pain, suggesting that a mast cell protease, tryptase released from BMMC on their degranulation might participate in the pain induction through activation of PAR2 receptor. When apyrase that degrades extracellular ATP was injected into MIA-induced osteoarthritic joint before injection of BMMCs, pain was not induced, suggesting that ATP may play a role in the activation of BMMCs. Injection of BMMC to MIA-induced osteoarthritic joints stimulate expression of IL-1b, IL-6, CXCL2, CCL2, and MMP9 gene.
|
| Academic Significance and Societal Importance of the Research Achievements |
変形性関節症(OA)は最も多い慢性関節疾患であり、高齢者の移動能を損なう最も大きな原因である。疼痛はOAの主要症状であるが、X線観察に基づく疾患の重篤度との間には関連が少ない。疼痛の起きる原因としくみを解明することは症状を緩和し機能改善の治療法開発に重要である。OAの疼痛に肥満細胞が関係する可能性は報告されているが、分子機構はまだほとんど未解明である。本研究では培養肥満細胞をOAの関節に移入する実験系を開発し、疼痛発生に肥満細胞トリプターゼが関与すること、肥満細胞の脱顆粒に細胞外ATPが関与することを示唆する結果を得た。これらの成果は新たな治療法の開発に寄与することが期待される。
|
Report
(5 results)
Research Products
(5 results)
