2021 Fiscal Year Final Research Report
Elucidation of the mechanism of thrombin in intervertebral disc degeneration
| Project/Area Number |
20K17995
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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 Yamanashi |
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Principal Investigator |
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| Project Period (FY) |
2020-04-01 – 2022-03-31
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| Keywords | 椎間板変性 / トロンビン / 血管新生 / マクロファージ |
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| Outline of Final Research Achievements |
With the aging of the population, musculoskeletal disorders due to low back pain have been associated with locomotive syndrome and an increase in the number of people requiring nursing care. Intervertebral disc degeneration is one of the causes of low back pain, and elucidating this mechanism is an urgent social issue. The applicant focused on the mechanism of degeneration from the outer layer of the intervertebral disc and investigated the inflammation and degeneration mechanism of thrombin, including angiogenesis.
The results of the study include: 1) expression of the thrombin receptor PAR1 in mouse intervertebral discs was confirmed; 2) MMP3 expression and disc degeneration were observed upon thrombin stimulation and were also suppressed by inhibition of PAR1; 3) VEGF was expressed in mouse intervertebral discs upon thrombin stimulation; 4) angiogenesis was observed in an artificial mouse disc degeneration model. angiogenesis in an artificial mouse model of disc degeneration.
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| Free Research Field |
椎間板変性
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| Academic Significance and Societal Importance of the Research Achievements |
正常椎間板は最大の無血管組織であり、その栄養のほとんどは椎体より終板を介して拡散することで得られる。外側線維輪細胞のみが周辺毛細血管より栄養されるが、変性椎間板では周辺血管より線維輪細胞のみならず、髄核細胞まで神経血管の新生が起こるとされるが詳細なメカニズムは不明であった。
仮説として、周辺毛細血管損傷と線維輪構造の損傷により椎間板外層より椎間板変性がもたらされることが考えられた。そこでトロンビンによって新たに変性をもたらす因子としてVEGFによる血管新生と外層線維輪細胞におけるマクロファージの役割、MMP3での直接的椎間板変性への作用について明らかにすることができた。
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