Elucidation of the synovial pathology in osteoarthritis by focusing on the involvement of fibrinolytic activity and development of pain.
| Project/Area Number |
20K09447
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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 |
Fukui Naoshi 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, 客員研究員 (10251258)
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| Co-Investigator(Kenkyū-buntansha) |
大橋 暁 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), 外科系臨床研究室, 医長 (20466767)
岩澤 三康 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), 診療部・整形外科, 部長 (60574093)
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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 |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2022: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2021: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2020: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
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| Keywords | 変形性関節症 / 滑膜 / 膝関節 / MMP-1 / 変形性膝関節症 / フレア / 関節液 / 滑膜病変 / 疼痛 / 痛み / 膝 / 関節 |
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| Outline of Research at the Start |
変形性関節症（以下、OA）では時にflareとも呼ばれる、痛みの急激な増悪を経験することがある。研究代表者らは今まで採取された関節液の解析によって、flareの時期には関節液中で線溶系の活性が亢進していることを見出した。線溶系の活性亢進は軟骨基質の変性を直接的に引き起こしうる。本研究ではこの知見をもとに、flareの時期に線溶活性が亢進する機序を明らかにすることを目的に研究を行う。本研究では滑膜が種々の細胞が混在する組織であることからsingle cell RNA sequencing を行って、病変を生じた滑膜においてどの細胞がどのように変化するのかを詳細に解明する。
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| Outline of Final Research Achievements |
In this study, synovial fluid samples obtained from osteoarthritic (OA) knees that underwent synovial flare were analyzed in order to determine the link between synovial pathology and cartilage degeneration. In the results, we found that the enzymic activity of MMP-1, but not that of MMP-2 or MMP-3, was enhanced during flare compared with the samples collected after resolution of flare. This result might explain why rapid cartilage degeneration occurs during flare, at least in a subset of patients. If the enhancement in MMP-1 activity in synovial fluid is a prevalent event across various OA knees, that could account for, at least in part, progression of the disease related to the synovial pathology. This finding might be crucial in understanding the pathology of OA. During this study period, we also found that the enhanced expression of urokinase which occurs in the synovium during flare could be induced by active TGF-β released from OA cartilage.
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| Academic Significance and Societal Importance of the Research Achievements |
膝OAは患者数の極めて多い疾患であるにもかかわらず、疾患の進行を抑止しうる治療法は確立されていない。本研究の結果から、滑膜病変に伴う関節軟骨の変性消失には、関節液中のMMP-1の活性亢進が関与する可能性が示された。もしMMP-1の活性亢進が滑膜性フレアの症例だけでなく膝OAの症例全般について認められる現象であるとすれば、MMP-1の活性抑制によってOAの進行が抑止される可能性も考えられる。OAの効果的な進行抑止法の確立は高齢者の自立喪失の予防の観点からも、また医療経済学的な観点からも重要である。本研究の成果はOAの進行抑止法の確立に繋がりうる点で社会的にも意義の高いものと考えられた。
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Report
(4 results)
Research Products
(39 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] Lumbar Fusion including Sacroiliac Joint Fixation Increases the Stress and Angular Motion at the Hip Joint: A Finite Element Study2022
Author(s)
Kozaki T, Hashizume H, Oka H, Ohashi S, Kumano Y, Yamamoto E, Minamide A, Yukawa Y, Iwasaki H, Tsutsui S, Takami M, Nakata K, Taniguchi T, Fukui D, Nishiyama D, Yamanaka M, Tamai H, Taiji R, Murata S, Murata A, Yamada H.
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Journal Title
Spine Surgery and Related Research
Volume: 6
Issue: 6
Pages: 681-688
DOI
ISSN
2432-261X
Year and Date
2022-11-27
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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[Journal Article] Serum Metabolomic Profiling in Rheumatoid Arthritis Patients With Interstitial Lung Disease: A Case-Control Study2020
Author(s)
Furukawa H, Oka S, 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
Front Med (Lausanne)
Volume: 17
Pages: 599794-599794
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Human Leukocyte Antigen in Japanese patients with idiopathic inflammatory myopathy.2019
Author(s)
Furukawa H, Oka S, Kawasaki A, Hidaka M, Shimada K, Kondo Y, Ihata A, Matsushita T, Matsumoto T, Hashimoto A, Matsumoto I, Komiya A, Kobayashi K, Osada A, Katayama M, Okamoto A, Setoguchi K, Kono H, Hamaguchi Y, Matsui T, Fukui N, Tamura H, Takehara K, Nagaoka S, Sugii S, Sumida T, Tsuchiya N, Tohma S.
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Journal Title
Mod Rheumatol.
Volume: in press
Issue: 4
Pages: 1-7
DOI
Related Report
Peer Reviewed
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[Presentation] 関節リウマチ関連間質性肺病変に関連する自己抗体2020
Author(s)
岡 笑美,古川 宏,島田 浩太,岡本 享,橋本 篤,小宮 明子,税所 幸一郎,吉川 教恵,片山 雅夫,松井 利浩,福井 尚志,右田 清志,當間 重人
Organizer
第64回日本リウマチ学会
Related Report
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[Presentation] 関節リウマチ関連間質性肺病変に関連する自己抗体2020
Author(s)
岡 笑美,古川 宏,島田 浩太,岡本 享,橋本 篤,小宮 明子,税所 幸一郎,吉川 教恵,片山 雅夫,松井 利浩,福井 尚志,右田 清志,當間 重人
Organizer
第74回国立病院総合医学会
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