Exploration of possible catabolic factors in osteoarthritis through the analysis of large numbers of human samples.

• Project/Area Number: 20390410
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Orthopaedic surgery
• Research Institution: Clinical Research Center for Allergy and Rheumatology, National Hospital Organization, Sagamihara National Hospital
• Principal Investigator: FUKUI Naoshi Clinical Research Center for Allergy and Rheumatology, National Hospital Organization, Sagamihara National Hospital, 病態総合研究室, 部長 (10251258)
• Co-Investigator(Kenkyū-buntansha): SUZUKI Ryuji 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), 診断・治療研究室, 室長 (70373470) ; MITOMI Hiroyuki 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), 病態総合研究部, 研究員 (90181940) ; 疋田 温彦 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), 病態総合研究部, 特別研究員 (60443397)
• Project Period (FY): 2008 – 2010
• Project Status: Completed (Fiscal Year 2010)
• Budget Amount: ¥20,020,000 (Direct Cost: ¥15,400,000、Indirect Cost: ¥4,620,000); Fiscal Year 2010: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000); Fiscal Year 2009: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000); Fiscal Year 2008: ¥14,820,000 (Direct Cost: ¥11,400,000、Indirect Cost: ¥3,420,000)
• Keywords: 変形性関節症 / 軟骨変性因子 / マイクロアレイ / 関節液 / 滑膜 / 関節軟骨 / サイトカイン

Research Abstract

In this project, we have obtained synovial and cartilage tissues and synovial fluid samples from a large number of knee OA patients at various disease severities, and conducted a series of gene expression and protein analyses. Through the analyses, we have constructed a data base about human OA tissues and synovial fluid, which we found highly useful in exploration of possible catabolic factors for cartilage in the disease. Utilizing this data base, we were able to identify several possible catabolic factors in OA. Through a series of analyses with the data, we have identified a possible mechanism for synovial changes in OA. Validation of the significance of these factors in the disease is a future problem which should be answered by subsequent studies.

Research Products

• [Journal Article] Aberrant p16^INK4a methylation is a frequent event in colorectal cancers : prognostic value and relation to mRNA expression and immunoreactivity. (2010)
  • Author(s): Mitomi H, Fukui N, Tanaka N, Kanazawa H, Saito T, Matsuoka T, Yao T.
  • Journal Title: J Cancer Res Clin Oncol 136 Pages: 323-331
• [Journal Article] Communication skills training on how to break bad news for Japanese nurses in oncology : effects of training on nurses' confidence and perceived effectiveness. (2010)
  • Author(s): Fukui S, Ogawa K, Fukui N.
  • Journal Title: J Cancer Educ 25 Pages: 116-119
• [Journal Article] New sequence variants in HLA class II/III region associated with susceptibility to knee osteoarthritis identified by genome-wide association study. (2010)
  • Author(s): Nakajima M, Takahashi A, Kou I, Rodriguez-Fontenla C, Gomez-Reino JJ, Furuichi T, Dai J, Sudo A, Uchida A, Fukui N, Kubo M, Kamatani N, Tsunoda T, Malizos KN, Tsezou A, Gonzalez A, Nakamura Y, Ikegawa S.
  • Journal Title: PLoS One 5 Pages: 9723-9723
• [Journal Article] Changes of human menisci in osteoarthritic knee joints. (2010)
  • Author(s): Katsuragawa Y, Saitoh K, Tanaka N, Wake M, Ikeda Y, Furukawa H, Tohma S, Sawabe M, Ishiyama M, Yagishita S, Suzuki R, Mitomi H, Fukui N.
  • Journal Title: Osteoarthritis and Cartilage 18 Pages: 1133-1143
• [Journal Article] Relationship between radiographic changes and symptoms or physical examination findings in subjects with symptomatic medial knee osteoarthritis : a three-year prospective study. (2010)
  • Author(s): Fukui N, Yamane S, Ishida S, Tanaka K, Masuda R, Tanaka N, Katsuragawa Y, Fukui S.
  • Journal Title: BMC Muscloskelet Disord 11 Pages: 269-269
• [Journal Article] Mew sequence variants in HLA class II/III region associated with sus-ceptibility to knee osteoarthritis identified by genome-wide association study (2010)
  • Author(s): Nakajima M, Fukui N, et al.(18名中10番目)
  • Journal Title: PLoS One Volume: 5
  • Peer Reviewed
• [Journal Article] Changes of human menisci in osteoarthritic knee joints. (2010)
  • Author(s): Katsuragawa Y, Fukui N, et al.(13名中ラスト)
  • Journal Title: Osteoarthritis and Cartilage Volume: 18 Pages: 1133-1143
  • Peer Reviewed
• [Journal Article] Relationship between radiographic changes and symptoms or physical examination findings in subjects with symptomatic medial knee osteo-arthritis : athree-year prospective study. (2010)
  • Author(s): Fukui N, Ikeda Y, et al.(8名中1番目)
  • Journal Title: BMC Muscloskeletal Disorder Volume: 11 Pages: 269-269
  • Peer Reviewed
• [Journal Article] Aberrant p16(INK4a)methylation is a frequent event in colorectal cancers : prognostic value and relation to mRNA expression and immunoreactivity (2010)
  • Author(s): Mitomi H, Fukui N, et al.
  • Journal Title: Journal of Cancer Research and Clinical Oncology 136(2) Pages: 323-331
  • Peer Reviewed
• [Journal Article] New sequence variants in HLA class II/III region associated with susceptibility to kneeosteoarthritis identified by genome-wide association study (2010)
  • Author(s): Nakajima M, Fukui N, et al.
  • Journal Title: ProsOne 5(3)
  • Peer Reviewed
• [Journal Article] Addition of an arch support improves the biomechanical effect of a laterally wedged insole. (2009)
  • Author(s): Nakajima K, Kakihana W, Nakagawa T, Mitomi H, Hikita A, Suzuki R, Akai M, Iwaya T, Nakamura K, Fukui N.
  • Journal Title: Gait and Posture 29 Pages: 208-213
• [Journal Article] Effect of communication skills training on nurses' detection of patient distress and related factors after cancer diagnosis : A randomized study. (2009)
  • Author(s): Fukui S, Ogawa K, Ohtsuka M, Fukui N.
  • Journal Title: Psycho-Oncology 18 Pages: 1156-1164
• [Journal Article] The interaction of monocytes with rheumatoid synovial cells is a key step in LIGHT-mediated inflammatory bone destruction. (2009)
  • Author(s): Ishida, S, Yamane S, Nakano S, Yanagimoto T, Hanamoto Y, Maeda-Tanimura M, Toyosaki-Maeda T, Ishizaki J, Matsuo Y, Fukui N, Itoh T, Ochi T, Suzuki R.
  • Journal Title: Immunology 128 (1 Suppl) Pages: 315-24
• [Journal Article] Involvement of a disintegrin and metalloproteinase 10 and 17 in shedding of tumor necrosis factor-α. (2009)
  • Author(s): Hikita A, Tanaka N, Yamane S, Ikeda Y, Furukawa H, Tohma S, Suzuki R, Tanaka S, Mitomi H, Fukui N.
  • Journal Title: Biocehm Cell Biol 87 Pages: 581-593
• [Journal Article] Involvement of a disintegrin and metalloproteinase 10 and 17 in shedding of tumor necrosis factor-α (2009)
  • Author(s): Hikita A, Fukui N, et al.
  • Journal Title: Biochemistry and Cell Biology 87(4) Pages: 581-593
  • Peer Reviewed
• [Journal Article] I. 身体活動の基礎 身体活動と筋骨格系 (2009)
  • Author(s): 福井尚志
  • Journal Title: 日本臨床 身体活動・運動と生活習慣病 運動生理学と最新の予防・治療 67 Pages: 42-47
• [Journal Article] LIGHT induces cell proliferation and inflammatory responses of rheumatoid arthritic synovial fibroblasts via lymphotaxin β receptor. (2008)
  • Author(s): Ishida S, Yamane S, Ochi T, Nakano S, Mori T, Juji T, Fukui N, Itoh T, Suzuki R.
  • Journal Title: J Rheumatol 35 Pages: 960-968
• [Journal Article] Common variants in DVWA on chromosome 3p24.3 are associated with susceptibility to knee osteoarthritis. (2008)
  • Author(s): Miyamoto Y, Shi D, Nakajima M, Ozaki K, Sudo A, Kotani A, Uchida A, Tanaka T, Fukui N, Tsunoda T, Takahashi A, Nakamura Y, Jiang Q, Ikegawa S.
  • Journal Title: Nat Genet 40 Pages: 994-998
• [Journal Article] Zonal gene expression of chondrocytes in osteoarthritic cartilage. (2008)
  • Author(s): Fukui N, Miyamoto Y, Nakajima M, Ikeda Y, Hikita A, Furukawa H, Mitomi H, Tanaka N, Katsuragawa Y, Yamamoto S, Sawabe M, Juji T, Mori T, Suzuki R, Ikegawa S.
  • Journal Title: Arthritis Rheum 58 Pages: 3843-3853
• [Journal Article] A randomized study assessing efficacy of communication skill training on patients' psychologic distress and coping : Nurses' communication with patients just after being diagnosed with cancer. (2008)
  • Author(s): Fukui S, Ogawa K, Ohtsuka M, Fukui N.
  • Journal Title: Cancer 113 Pages: 1462-1470
• [Journal Article] Inhibition of Src homology 2 domain-containing protein tyrosine phosphatase substrate-1 reduces the severity of collagen-induced arthritis. (2008)
  • Author(s): Tanaka K, Horikawa T, Suzuki S, Kitaura K, Watanabe J, Gotoh A, Shiobara N, Yamane S, Suzuki R, Fukui N, Ochi T.
  • Journal Title: J Rheumatol 35 Pages: 2316-2324
• [Journal Article] Zonal gene expression of chondrocytes in osteoarthritic cartilage (2008)
  • Author(s): Fukui N, Miyamoto Y, Nakajima M, Ikeda Y, et al.
  • Journal Title: Arthritis Rheum 58 Pages: 3843-3853
  • Peer Reviewed
• [Journal Article] Common variants in DVWA on chromosome 3p24. 3 are associated with susceptibility to knee osteoarthritis (2008)
  • Author(s): Miyamoto Y, Shi D, Nakajima M, Fukui N, et al.
  • Journal Title: Nat Genet 40 Pages: 994-998
  • Peer Reviewed
• [Journal Article] Inhibition of Src homology 2 domain-containing protein tyrosine phosphatase substrate-1 reduces the severity of collagen-induced arthritis (2008)
  • Author(s): Tanaka K, Horikawa T, Suzuki S, Fukui N, et al
  • Journal Title: J Rheumatol 35 Pages: 2316-2324
  • Peer Reviewed
• [Journal Article] avR5 integrin promotes dedifferentiation of monolayer-cultured chondro-cytes.
  • Author(s): Fukui N, Ikeda Y, et al.(14名中1番目)
  • Journal Title: Arthritis and Rheumatism Volume: in press
  • Peer Reviewed
• [Journal Article] The interaction of monocytes with rheumatoid synovial cells is a key step in LIGHT-mediated inflammatory bone destruction
  • Author(s): Ishida, S, Yamane S, Nakano S, Yanagimoto T, et al.
  • Journal Title: Immunology (in press)
  • Peer Reviewed
• [Presentation] Synovium-another culprit in OA? (2011)
  • Author(s): Fukui N.
  • Organizer: 第24回日本軟骨代謝学会
  • Place of Presentation: 福岡市
• [Presentation] 変形性関節症では軟骨変性部でIGFシグナルの低下によって基質産生が低下・している (2011)
  • Author(s): 田中信帆、福井尚志, ほか
  • Organizer: 第24回日本軟骨代謝学会
  • Place of Presentation: 福岡市
• [Presentation] 変形性関節症における軟骨変性には局所的なTIMPの発現低下が関与する (2011)
  • Author(s): 山口鉄生、福井尚志, ほか
  • Organizer: 第24回日本軟骨代謝学会
  • Place of Presentation: 福岡市
• [Presentation] Exploration of possible catabolic factors for cartilage matrix in osteoarthritic synovial fluid. (2010)
  • Author(s): Fukui N, Ikeda Y, Tanaka N, Wake M, Ohmori M, Yamaguchi T, Furukawa H, Touma S, Miyamoto Y, Tashiro T, Katsuragawa Y.
  • Organizer: 2010 World Congress on Osteoarthritis.
  • Place of Presentation: Brussels, Belgium.
• [Presentation] Dedifferentiation of monolayer cultured chondrocytes could be promoted by αvβ5 and α5β1 integrins. (2010)
  • Author(s): Fukui N.
  • Organizer: Osteoarthritis Research Society International, 2010 China Forum.
  • Place of Presentation: Nanjing, China.
• [Presentation] Exploration of possible catabolic factors for cartilage matrix in osteo-arthritic synovial fluid. (2010)
  • Author(s): Fukui N, et al.
  • Organizer: 2010 World Congress on Osteoarthritis
  • Place of Presentation: Brussels, Belgium
• [Presentation] Progression of symptomatic medial knee osteoarthritis.Relationship Between radiographic changes and symptoms.A 3-year prospective study. (2010)
  • Author(s): Fukui N, et al.
  • Organizer: 第2回日本関節鏡・膝スポーツ整形外科学会
  • Place of Presentation: 沖縄市
• [Presentation] Dedifferentiation of monolayer cultured chondrocytes could be promoted by av(35 and a5β1 integrins (2010)
  • Author(s): Fukui N
  • Organizer: The 1^<st> OAR, SI China Forum
  • Place of Presentation: Nanjing, People's Republic of China
• [Presentation] レーザー・キャプチャー・マイクロダイセクションのヒト軟骨組織への応用-変形性関節症の病態解明への試み (2010)
  • Author(s): 福井尚志
  • Organizer: 第31回レーザー医学会総会
  • Place of Presentation: 名古屋
• [Presentation] 内側型膝OAの進行過程 -保存的治療例におけるレントゲン、愁訴、臨床所見の経時的変化- (2009)
  • Author(s): 福井尚志、ほか
  • Organizer: 第1回日本関節鏡・膝・スポーツ整形外科学会
  • Place of Presentation: 札幌
• [Presentation] 変形性関節症の病態 -最近の知見と滑膜病変に関する我々の検討結果- (2009)
  • Author(s): 福井尚志
  • Organizer: 第27回 日本骨代謝学会
  • Place of Presentation: 大阪
• [Presentation] 大腿骨頚部骨折、転子部骨折の機能予後とそれに影響を及ぼす要因 (2009)
  • Author(s): 福井尚志、ほか
  • Organizer: 第58回 東日本整形災害外科学会
  • Place of Presentation: 小樽市
• [Presentation] ヒト変形性関節症罹患軟骨における anabolic factor の発現の検討 -変性部における軟骨基質発現低下の機序解明の試み- (2009)
  • Author(s): 福井尚志、ほか
  • Organizer: 第24回日本整形外科学会基礎学術集会
  • Place of Presentation: 横浜
• [Presentation] 変形性関節症における関節液中の軟骨変性因子の探索 (2009)
  • Author(s): 福井尚志、ほか
  • Organizer: 第24回日本整形外科学会基礎学術集会
  • Place of Presentation: 横浜
• [Presentation] Addition of an arch support improves the biomechanical effect of a laterally wedged insole. (2008)
  • Author(s): Nakajima K, Kakihana W, Nakagawa T, Mitomi H, Hikita A, Suzuki R, Akai M, Iwaya T, Nakamura K, Fukui N.
  • Organizer: 2008 World Congress on Osteoarthritis.
  • Place of Presentation: Roma, Italy
• [Presentation] Zonal gene expression of chondrocytes in osteoarthritis cartilage. (2008)
  • Author(s): Fukui N, Miyamoto Y, Nakajim M, Ikeda Y, Hikita A, Furukawa H, Mitomi H, Tanaka N, Katsuragawa Y, Yamamoto S, Sawabe M, Juji T, Mori T, Suzuki R, Ikegawa S.
  • Organizer: 2008 World Congress on Osteoarthritis.
  • Place of Presentation: Roma, Italy.
• [Presentation] Altered chondrocyte metabolism in osteoarthritic cartilage. Can it be normalized?. (2008)
  • Author(s): Fukui N.
  • Organizer: 13th Congress on the Asia Pacific League of Associations for Rheumatology.
  • Place of Presentation: Yokohama.
• [Presentation] インテグリンの活性抑制は変形性関節症罹患軟骨における病的コラーゲンの発現を軽減し、培養軟骨細胞の脱分化を抑制する (2008)
  • Author(s): 福井尚志, 池田泰子, 疋田温彦, 三富弘之, 十字琢夫, ほか
  • Organizer: 第23回日本整形外科学会基礎学術集会
  • Place of Presentation: 京都
• [Presentation] 変形性関節症罹患軟骨における軟骨細胞の代謝活性の検討-マイクロアレイによる軟骨各層の遺伝子発現の解析結果から- (2008)
  • Author(s): 福井尚志, 宮本恵成, 中島正宏, 池田泰子, ほか
  • Organizer: 第23回日本整形外科学会基礎学術集会
  • Place of Presentation: 京都
• [Presentation] 変形性関節症における軟骨細胞の基質産生の変化-軟骨細胞の基質産生の正常化は可能か?- (2008)
  • Author(s): 福井尚志
  • Organizer: 第26回日本骨代謝学会学術集会
  • Place of Presentation: 大阪
• [Presentation] Zonal gene expression of chondrocytes in osteoarthritis cartilage (2008)
  • Author(s): Fukui N, Miyamoto Y, Nakajim M, Ikeda Y, et al.
  • Organizer: 2008 World Congress on Osteoarthritis
  • Place of Presentation: Roma, Italy
• [Presentation] Altered chondrocyte metabolism in osteoarthritic cartilage. Can it be normalized? (2008)
  • Author(s): Fukui N
  • Organizer: 13th Congress on the Asia Pacific League of Associations for Rheumatology
  • Place of Presentation: Yokohama, Japan
• [Book] In : Laser capture microdissection : methods and applications. 2nd Ed. Murray GI, editor. London : Springer-Verlag
  • Author(s): Fukui N, Ikeda Y, Tanaka N.
  • Publisher: The use of laser capture microdissection on adult human articular cartilage for gene expression analysis.(in press.)
• [Book] methods and applications.(Murray GI, editor, Laser capture microdissection 2^<nd>Ed)
  • Author(s): Fukui N, et al.(3名中1番目)
  • Publisher: Springer-Verlag in press
• [Book] Laser capture microdissection : methods and applications. 2nd Ed.Murray GI, editor
  • Author(s): Fukui N, Ikeda Y, Tanaka N
  • Publisher: The use of laser capture microdissection on adult human articular cartilage for gene expression analysis(in press)
• [Remarks] ホームページ等
  • URL: http://www.hosp.go.jp/~sagami/rinken/crc/index.html
• [Remarks]
  • URL: http://www.hosp.go.jp/~sagami/rinken/crc/dl/081002.pdf
• [Remarks]
  • URL: http://www.hosp.go.jp/~sagami/rinken/crc/dl/071003.pdf