2022 Fiscal Year Final Research Report
Elucidation of the mechanism(s) underlying the progression of osteoarthritis by focusing on the phenotypic change of chondrocytes in degenerated cartilage.
| Project/Area Number |
20K09470
|
|---|
| 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 | Clinical Research Center for Allergy and Rheumatology, National Hospital Organization, Sagamihara National Hospital |
|---|
Principal Investigator |
Tanaka Nobuho 独立行政法人国立病院機構(相模原病院臨床研究センター), 外科系リウマチ研究室, 研究員 (60530920)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
福井 尚志 独立行政法人国立病院機構(相模原病院臨床研究センター), 政策医療企画部, 特別研究員 (10251258)
|
|---|
| Project Period (FY) |
2020-04-01 – 2023-03-31
|
| Keywords | 変形性関節症 / 軟骨 / タンパク分解酵素 / 膝関節 |
|---|
| Outline of Final Research Achievements |
n osteoarthritis (OA), cartilage degeneration is induced by various metalloproteinases including several MMPs and ADAMTSs. These enzymes are initially expressed in inactive proforms, and have to undergo activation to be enzymatically active. Therefore, their activation is critical in cartilage degeneration in OA. However, at present, little is known about the mechanism(s) underlying their activation in OA cartilage. In this study, we performed analyses of OA cartilage and found that the expression of two plasminogen activators and plasmin activity were enhanced in degenerated areas of OA cartilage compared to preserved areas. Between the two activators, tPA was more abundant in quantity than uPA, and tPA was considered more responsible for the enhanced plasmin activity in degenerated areas. Since plasmin is known to be a potent activator of various MMPs, the finding of this study may be crucial in understanding the mechanism of cartilage degeneration in OA.
|
| Free Research Field |
関節リウマチ、変形性関節症
|
| Academic Significance and Societal Importance of the Research Achievements |
変形性関節症の罹患者数は社会の高齢化に伴い増加の一途をたどっているが、病態にはなお不明な点が多く、このため疾患の進行を抑止できる治療法は確立されていない。本研究の結果からOAの軟骨変性部においてプラスミンの活性が亢進していることが明らかになったが、もしプラスミン活性がOAの軟骨変性に大きく関与しているとすれば、本研究の知見からOAの進行を抑止する治療法が確立される可能性も考えられる。OAの進行を効果的に抑制できる治療法の確立は、高齢者の自立喪失を抑止する観点からも極めて重要であり、その点で本研究は社会的にも意義の高い研究と言いうる。
|
