| Project/Area Number |
18K17050
|
|---|
| Research Category |
Grant-in-Aid for Early-Career Scientists
|
| Allocation Type | Multi-year Fund |
|---|
| Review Section |
Basic Section 57030:Conservative dentistry-related
|
|---|
| Research Institution | Okayama University |
|---|
Principal Investigator |
|
|---|
| Project Period (FY) |
2018-04-01 – 2020-03-31
|
| Project Status |
Completed (Fiscal Year 2019)
|
| Budget Amount *help |
¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
Fiscal Year 2019: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2018: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
|
|---|
| Keywords | HMGB1 / 抜歯窩創傷治癒 / 幹細胞 / M1マクロファージ / 抜歯 / 炎症 / 免疫細胞 / 骨治癒 / 血管新生 / 骨再生 |
|---|
| Outline of Final Research Achievements |
HMGB1 is released from a variety of cells into the extracellular milieu in response to inflammatory stimuli. We reported that secreted HMGB1 is involved in wound healing after tooth extraction, however, we still do not know the detailed mechanism. In this study, we examined that gene expression levels and MSC localization around tooth extraction sockets. The gene expressions related to inflammation, MSC recruitment, MSC markers, bone regeneration were increased after murine tooth extraction, and there were decreased in the anti-HMGB1 antibody administration. The localization of Nanog positive cells was low in anti-HMGB1 antibody administration group compared to the control group. Anti-HMGB1 administration decreased the ration of M1 macrophages and it also decreased CCL2 and CCR2 gene expression. These results suggested that HMGB1 promotes M1 macrophage polarization and CCL2 production and then may cause MSC recruitment during wound healing after tooth extraction.
|
| Academic Significance and Societal Importance of the Research Achievements |
HMGB1は，敗血症や脳疾患などに対して抗HMGB1抗体を投与する臨床研究も盛んに行われている。近年では組織修復にも関与することが報告されてきた。我々はこれまでに抜歯窩の治癒過程においてHMGB1を阻害すると，治癒遅延を起こすことを明らかとした。本研究はそれをさらに発展させ，抜歯後に分泌されたHMGB1はマクロファージのM1への分極を促し，さらにCCL2の産生を介して幹細胞の遊走に関わることが明らかとなった。
高齢者や免疫が低下した患者は治癒が遅延することが報告されている。今後このような免疫低下した患者に対して，HMGB1を投与する新たな再生療法へとつながる可能性がある。
|
