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
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Review Section |
Basic Section 56020:Orthopedics-related
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| Research Institution | Clinical Research Center for Allergy and Rheumatology, National Hospital Organization, Sagamihara National Hospital |
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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)
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| 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)
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| Project Period (FY) |
2020-04-01 – 2023-03-31
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| Project Status |
Completed (Fiscal Year 2022)
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| Budget Amount *help |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2022: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2021: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
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| Keywords | 変形性関節症 / 軟骨 / タンパク分解酵素 / 膝関節 / 変形性膝関節症 / プラスミン / TGF-beta / プラスミノーゲン・アクチベーター / 軟骨変性 / 痛み / 関節 / 膝 |
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| Outline of Research at the Start |
研究代表者らは変形性関節症（OA）に罹患した関節軟骨の解析を進める中、軟骨の肉眼的な変性部で urokinase（uPA）の発現が亢進し、プラスミン活性が上昇、 さらにOA の痛みに深く関与する nerve growth factor（NGF）の発現も亢進していることを見出した。プラスミンはそれ自体が様々なタンパクを分解する作用を持つほか、MMP を活性化することによっても軟骨基質の変性を強力に推し進め得る。本研究では、これらの知見に基づき、軟骨変性部でプラスミン活性が亢進しNGF の発現が上昇する機序を明らかにする。
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| 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.
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| 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。
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Report
(4 results)
Research Products
(25 results)
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[Journal Article] Accumulation of polyunsaturated fatty acid-derived metabolites in the sarcopenic muscle of aging mice2023
Author(s)
Kadoguchi T, Shimada K, Fukui N, Tanaka N, Tsuno H, Shiozawa T, Fukao K, Nishitani-Yokoyama M, Isoda K, Matsushita S, Yokoyama N, Daida H.
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Journal Title
Geriatrics and Gerontology International
Volume: 23
Issue: 4
Pages: 297-303
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Antibodies against serum anti-melanoma differentia-tion-associated gene 5 in rheumatoid arthritis patients with chronic lung diseases.2023
Author(s)
Oka S, Higuchi T, Furukawa H, Shimada K, Okamoto A, Hashimoto A, Komiya A, Saisho K, Yoshikawa N, Katayama M, Matsui T, Fukui N, Migita K, Tohma S
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Journal Title
Medicina (Kaunas, Lithuania)
Volume: 59
Issue: 2
Pages: 363-363
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Predisposition of HLA-DRB1*04:01/*15 heterozygous genotypes to Japanese mixed connective tissue disease.2022
Author(s)
Oka S, Higuchi T, Furukawa H, Shimada K, Hashimoto A, Komiya A, Matsui T, Fukui N, Suematsu E, Ohno S, Kono H, Katayama M, Nagaoka S, Migita K, Tohma S.
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Journal Title
Scientific Reports
Volume: 12
Issue: 1
Pages: 9916-9916
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Physician and patient perceptions of surgical procedures for osteoarthritis of the knee in the United States, Europe, and Japan: results of a real-world study2022
Author(s)
Fukui N, Conaghan PG, Togo K, Ebata N, Abraham L, Jackson J, Berry M, Cappelleri JC, Pandit H.
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Journal Title
BMC Musculoskeletal Disorders
Volume: 23
Issue: 1
Pages: 1065-1065
DOI
Related Report
Peer Reviewed / Int'l Joint Research
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