Development of novel treatment of rheumatoid arthritis by regulation of adiponectin

• Project/Area Number: 24791542
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Orthopaedic surgery
• Research Institution: Osaka University
• Principal Investigator: EBINA Kosuke 大阪大学, 医学(系)研究科(研究院), 助教 (70612076)
• Project Period (FY): 2012-04-01 – 2014-03-31
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2013: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000); Fiscal Year 2012: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: アディポネクチン / 関節リウマチ / プログラニュリン / ApoE

Research Abstract

We established 300 RA patients clinical database including severity and extent of joint destruction. We have previously reported that severity of RA evaluated by the extent of joint destruction is associated with serum adiponectin (APN)levels. In addition, APN and complement C1q forms complex (APN-C1q) in human serum and associate with the risk of cardiovascular events of type2 diabetes. From our results, serum APN-C1q levels of RA patients were significantly higher than that of age-and-BMI matched controls, and also showed stronger correlation with severity and extent of joint destruction compared to serum APN and C1q levels, respectively. Monitoring serum APN-C1q levels may be a novel predictive factor and of RA joint destruction and its clinical application as treatment target is expected.

Research Products

• [Journal Article] Autoantibodies to IgG/HLA class II complexes are associated with rheumatoid arthritis susceptibility (2014)
  • Author(s): Jin H, Arase N, Hirayasu K, Kohyama M, Suenaga T, Saito F, Tanimura K, Matsuoka S, Ebina K, et al
  • Journal Title: Proc Natl Acad Sci U S A Volume: 11;111(10) Pages: 3787-92
  • Peer Reviewed
• [Journal Article] Autoantibodies to IgG/HLA class II complexes are associated with rheumatoid arthritis susceptibility (2014)
  • Author(s): Jin H, Arase N, Hirayasu K, Kohyama M, Suenaga T, Saito F, Tanimura K, Matsuoka S, Ebina K, Shi K, Toyama-Sorimachi N, Yasuda S, Horita T, Hiwa R, Takasugi K, Ohmura K, Yoshikawa H, Saito T, Atsumi T, Sasazuki T, Katayama I, Lanier LL, Arase H
  • Journal Title: Proceedings of National Academy of Science USA Volume: 111 Issue: 10 Pages: 3787-3792
  • DOI: 10.1073/pnas.1401105111
  • Peer Reviewed / Open Access
• [Journal Article] Oxygen and air nanobubble water solution promote the growth of plants, fishes, and mice (2013)
  • Author(s): Ebina K, Shi K, Hirao M, Hashimoto J, Kawato Y, Kaneshiro S, Morimoto T, Koizumi K, Yoshikawa H
  • Journal Title: PLoS One Volume: 5;8(6)
  • Peer Reviewed
• [Journal Article] IL-6 negatively regulates osteoblast differentiation through the SHP2/MEK2 and SHP2/Akt2 pathways in vitro (2013)
  • Author(s): Kaneshiro S, Ebina K, Shi K, Hirao M, Hashimoto J, Morimoto T, Koizumi K, Yoshikawa H.
  • Journal Title: Journal of Bone and Mineral Metabolism Volume: (Epub ahead of print)
  • Peer Reviewed
• [Journal Article] Vitamin K2 administration is associated with decreased disease activity in patients with rheumatoid arthritis (2013)
  • Author(s): Ebina K, Shi K, Hirao M, Kaneshiro K, Morimoto T, Koizumi K, Yoshikawa K, Hashimoto J
  • Journal Title: ModRheumatol Volume: 23(5) Pages: 1001-7
  • NAID: 10031201160
  • Peer Reviewed
• [Journal Article] Retention of Tocilizumab and Anti-Tumor Necrosis Factor Drugs in the Treatment of Rheumatoid Arthritis (2013)
  • Author(s): Hishitani Y, Ogata A, Shima Y, Hirano T, Ebina K., et al
  • Journal Title: Scand J Rheumatol Volume: 42(4) Pages: 253-9
  • Peer Reviewed
• [Journal Article] Prevalence of gastroesophageal reflux disease symptoms and related factors in patients with rheumatoid arthritis (2013)
  • Author(s): Nampei A, Shi K, Ebina K, Tomita T, Sugamoto K, Yoshikawa H, Hirao M, Hashimoto J
  • Journal Title: J Clin Biochem Nutr Volume: 52(2) Pages: 179-84
  • NAID: 130004466715
  • Peer Reviewed
• [Journal Article] Use of a custom-made surgical guide in total ankle arthroplasty in rheumatoid arthritis cases (2013)
  • Author(s): Hirao M, Oka K, Ikemoto S, Nakao R, Tsuboi H, Nampei A, Akita S, Shi K, Ebina K, et al
  • Journal Title: Techniques in Orhopaedics Volume: (under publish)
  • Peer Reviewed
• [Journal Article] Oxygen and air nanobubble water solution promote the growth of plants, fishes, and mice. (2013)
  • Author(s): Ebina K, Shi K, Hirao M, Hashimoto J, Kawato Y, Kaneshiro S, Morimoto T, Koizumi K, Yoshikawa H.
  • Journal Title: PLoS One. Volume: 8(6) Issue: 6 Pages: e65339-e65339
  • DOI: 10.1371/journal.pone.0065339
  • Peer Reviewed
• [Journal Article] IL-6 negatively regulates osteoblast differentiation through the SHP2/MEK2 and SHP2/Akt2 pathways in vitro. (2013)
  • Author(s): Kaneshiro S, Ebina K, Shi K, Hirao M, Hashimoto J, Morimoto T, Koizumi K,
  • Journal Title: Journal of Bone and Mineral Metabolism. Volume: Epub ahead of print
  • Peer Reviewed
• [Journal Article] Prevalence of gastroesophageal reflux disease symptoms and related factors in patients with rheumatoid arthritis (2013)
  • Author(s): Nampei A, Shi K, Ebina K, Tomita T, Sugamoto K, Yoshikawa H, Hirao M, Hashimoto J.
  • Journal Title: Journal of Clinical Biochemistry and Nutrition Volume: 52 Issue: 2 Pages: 179-184
  • DOI: 10.3164/jcbn.12-83
  • NAID: 130004466715
  • ISSN: 0912-0009, 1880-5086
  • Peer Reviewed
• [Journal Article] Vitamin K2 administration is associated with decreased disease activity in patients with rheumatoid arthritis. (2013)
  • Author(s): Kosuke Ebina, Kenrin Shi, Makoto Hirao, Shoichi Kaneshiro, Tokimitsu Morimoto, Kota Koizumi, Hideki Yoshikawa, Jun Hashimoto.
  • Journal Title: Mod Rheumatol. Volume: 23(5) Issue: 5 Pages: 1001-7
  • DOI: 10.1007/s10165-012-0789-4
  • NAID: 10031201160
  • Peer Reviewed
• [Journal Article] Retention of tocilizumab and anti-tumour necrosis factor drugs in the treatment of rheumatoid arthritis. (2013)
  • Author(s): Hishitani Y, Ogata A, Shima Y, Hirano T, Ebina K, Kunugiza Y, Shi K, Narazaki M, Hagihara K, Tomita T, Yoshikawa H, Tanaka T, Kumanogoh A
  • Journal Title: Scandinavian Journal of Rheumatology Volume: 42 Issue: 4 Pages: 253-259
  • DOI: 10.3109/03009742.2012.762037
  • Peer Reviewed
• [Journal Article] Use of a custom-made surgical guide in total ankle arthroplasty in rheumatoid arthritis cases. (2013)
  • Author(s): Hirao M, Oka K, Ikemoto S, Nakao R, Tsuboi H, Nampei A, Akita S, Shi K, Ebina K.
  • Journal Title: Techniques in Orhopaedics. Volume: Epub ahead of print
  • Peer Reviewed
• [Journal Article] Vitamin K2 administration is associated with decreased disease activity in patients with rheumatoid arthritis (2013)
  • Author(s): Kosuke Ebina
  • Journal Title: Mod Rheumatol Volume: 未
  • NAID: 10031201160
  • Peer Reviewed
• [Journal Article] Nkx3.2 promotes primary chondrogenic differentiation by upregulating col2a1 transcription (2012)
  • Author(s): Kawato Y, Hirao M, Ebina K, Shi K, Hashimoto J, Honjo Y, Yoshikawa H, Myoui A.
  • Journal Title: PLoS One Volume: 7(4)
  • Peer Reviewed
• [Journal Article] Hypoxia favors maintenance of the vascular smooth muscle cell phenotype in culture (2012)
  • Author(s): Yamasaki N, Hirao M, Kawato Y, Ebina K, Oze H, Nampei A, Shi K, Yoshikawa H, Hashimoto J
  • Journal Title: J Biochem Mol Toxicol Volume: 26(10) Pages: 381-3
  • Peer Reviewed
• [Journal Article] Impact of medium volume and oxygen concentration in the incubator on pericellular oxygen concentration and differentiation of murine chondrogenic cell culture (2012)
  • Author(s): Oze H, Hirao M, Ebina K, Shi K, Kawato Y, Kaneshiro S, Yoshikawa H, Hashimoto J.
  • Journal Title: In Vitro Cell Dev Biol Anim Volume: 48(2) Pages: 123-30
  • Peer Reviewed
• [Presentation] 脂肪細胞分泌因子アディポネクチン(APN)と補体C1q の複合体(APN-C1q)の血中濃度は非RA 患者よりRA 患者で有意に高値でありかつ破壊関節数による重症度と相関する (2014)
  • Author(s): 蛯名耕介, 史賢林, 吉川秀樹
  • Organizer: 第58回日本リウマチ学会学術集会
  • Place of Presentation: 東京
• [Presentation] 成長因子Progranulin ノックアウトマウスは重度の骨粗鬆症を呈する (2014)
  • Author(s): 野口貴明, 蛯名耕介, 史賢林, 吉川秀樹
  • Organizer: 第58回日本リウマチ学会学術集会
  • Place of Presentation: 東京
• [Presentation] 脂質運搬蛋白ApolipoproteinE ノックアウトマウスは重度の骨粗鬆症を呈する (2014)
  • Author(s): 野口貴明, 蛯名耕介, 史賢林, 吉川秀樹
  • Organizer: 第87回日本整形外科学会学術集会
  • Place of Presentation: 神戸
• [Presentation] 成長因子Progranulin ノックアウトマウスは重度の骨粗鬆症を呈する (2014)
  • Author(s): 野口貴明, 蛯名耕介, 史賢林, 吉川秀樹
  • Organizer: 第87回日本整形外科学会学術集会
  • Place of Presentation: 神戸
• [Presentation] 脂肪細胞分泌因子アディポネクチン（APN）と補体C1qの複合体（APN-C1q）の血中濃度は非RA患者よりRA患者で有意に高値でありかつ破壊関節数による重症度と相関する (2014)
  • Author(s): 蛯名 耕介
  • Organizer: 日本リウマチ学会
  • Place of Presentation: 東京
• [Presentation] 成長因子Progranulinノックアウトマウスは重度の骨粗鬆症を呈する (2014)
  • Author(s): 野口 貴明、 蛯名 耕介
  • Organizer: 日本リウマチ学会
  • Place of Presentation: 東京
• [Presentation] 脂質運搬蛋白Apolipoprotein Eノックアウトマウスは重度の骨粗鬆症を呈する (2014)
  • Author(s): 野口 貴明、 蛯名 耕介
  • Organizer: 日本整形外科学会
  • Place of Presentation: 神戸
• [Presentation] Assessment of Time-Dependent Coronal Laxity in Deep Flexion After Posterior-Stabilized Total Knee Arthroplasty (2014)
  • Author(s): Kosuke Ebina
  • Organizer: 2014 ICJR Pan Pacific Orthopaedic Congress
  • Place of Presentation: Hawaii(アメリカ合衆国）
• [Presentation] 関節リウマチに伴う骨粗鬆症患者と閉経後骨粗鬆症患者に対する12か月間のテリパラチド20μg連日投与の治療効果の比較検討 (2013)
  • Author(s): 蛯名 耕介
  • Organizer: 日本リウマチ学会
  • Place of Presentation: 京都
• [Presentation] 関節リウマチにおけるエタネルセプトとアダリムマブの一次・二次無効に対するメソトレキセートとステロイドの影響についての検討 (2013)
  • Author(s): 蛯名 耕介
  • Organizer: 日本リウマチ学会
  • Place of Presentation: 京都
• [Presentation] "関節リウマチ患者の前足部術後の歩行時足底圧分布についての解析 (2013)
  • Author(s): 蛯名 耕介
  • Organizer: 日本リウマチ学会
  • Place of Presentation: 京都
• [Presentation] 関節リウマチ患者においてビタミンK2投与群では非投与群と比較して疾患活動性が有意に低値を示す (2013)
  • Author(s): 蛯名 耕介
  • Organizer: 日本整形外科学会
  • Place of Presentation: 広島
• [Presentation] 転写因子Nkx3.2は2型コラーゲンとアグリカン転写活性を促進する初期軟骨分化に必須の因子である (2013)
  • Author(s): 蛯名 耕介
  • Organizer: 日本骨代謝学会
  • Place of Presentation: 神戸
• [Presentation] ミノドロネート投与前・3カ月後の骨代謝マーカーの推移 ―単剤投与／エルデカルシドール・ビタミンK2併用／ アレンドロネート・リセドロネートからの切り替えでの比較検討－ (2013)
  • Author(s): 蛯名 耕介
  • Organizer: 日本骨粗鬆症学会
  • Place of Presentation: 大阪
• [Presentation] Influence of concomitant Methotrexate and Prednisolone on drug inefficacy of Etanercept and Adalimumab in patients with rheumatoid arthritis (2013)
  • Author(s): Kosuke Ebina
  • Organizer: European League Against Rheumatism Congress
  • Place of Presentation: Madrid（スペイン）
• [Presentation] Assessment of plantar pressure distribution during walking after forefoot surgery in patients with rheumatoid arthritis (2013)
  • Author(s): Kosuke Ebina
  • Organizer: European League Against Rheumatism Congress
  • Place of Presentation: Madrid（スペイン）
• [Presentation] Transcription factor Nkx3.2 plays crucial role in primary chondrogenesis by up-regulating type II collagen a1 transcription activity (2013)
  • Author(s): Kosuke Ebina
  • Organizer: European Symposium on Calcified Tissues
  • Place of Presentation: Lisbon（ポルトガル）
• [Presentation] Vitamin K2 administration is associated with decreased disease activity in patients with rheumatoid arthritis (2013)
  • Author(s): Kosuke Ebina
  • Organizer: European Symposium on Calcified Tissues
  • Place of Presentation: Lisbon（ポルトガル）
• [Presentation] 関節リウマチ（RA）に伴う骨粗鬆症患者と閉経後骨粗鬆症患者に対する12か月間のテリパラチド20μg連日投与の治療効果の比較検討 (2013)
  • Author(s): 蛯名 耕介
  • Organizer: 日本骨代謝学会
  • Place of Presentation: 神戸
• [Presentation] 関節リウマチ患者においてビタミンK2投与群では非投与群と比較して疾患活動性が有意に低値を示す (2013)
  • Author(s): 蛯名 耕介
  • Organizer: 日本骨代謝学会
  • Place of Presentation: 神戸
• [Presentation] TKA術後の経時的屈曲位内外反バランスの推移 ～深屈曲位の内側ギャップは術後24カ月で有意に低下する～ (2013)
  • Author(s): 蛯名 耕介
  • Organizer: 中部日本整形外科災害外科学会・学術集会
  • Place of Presentation: 名古屋
• [Presentation] 関節リウマチにおけるエタネルセプトとアダリムマブの無効に対するDMARDsとステロイドの影響についての検討 (2013)
  • Author(s): 蛯名 耕介
  • Organizer: 中部日本整形外科災害外科学会・学術集会
  • Place of Presentation: 名古屋
• [Presentation] 関節リウマチ前足部術後の足底圧分布についての解析 (2013)
  • Author(s): 蛯名 耕介
  • Organizer: 中部日本整形外科災害外科学会・学術集会
  • Place of Presentation: 名古屋
• [Presentation] 多発性骨腫瘍様病変を伴った巨大副甲状腺腫瘍摘出後にHungry Bone Syndromeを来した16歳男子の一例 (2013)
  • Author(s): 蛯名 耕介
  • Organizer: 日本骨粗鬆症学会
  • Place of Presentation: 大阪
• [Presentation] 関節リウマチに伴う骨粗鬆症患者と閉経後骨粗鬆症患者に 対する18か月間のテリパラチド20μg連日投与の 治療効果の比較検討 (2013)
  • Author(s): 蛯名 耕介
  • Organizer: 日本骨粗鬆症学会
  • Place of Presentation: 大阪
• [Presentation] 関節リウマチ前足部術後の足底圧分布についての解析－中足骨頭の温存が荷重分圧に及ぼす影響について－ (2013)
  • Author(s): 蛯名 耕介
  • Organizer: 日本足の外科学会
  • Place of Presentation: 仙台
• [Presentation] 関節リウマチ患者においてビタミンK2投与群では非投与群と比較して血中CRP・MMP-3濃度が有意に低値を示す (2012)
  • Author(s): 蛯名 耕介
  • Organizer: 日本リウマチ学会学術集会
  • Place of Presentation: 東京
• [Book] 最新関節リウマチ学 (2014)
  • Author(s): 蛯名 耕介
  • Total Pages: 5
  • Publisher: 日本臨牀社
• [Book] 臨床リウマチ25巻1号 (2013)
  • Author(s): 蛯名耕介
• [Book] 生活習慣病改善指導士ハンドブック (2013)
  • Author(s): 蛯名 耕介
  • Total Pages: 5
  • Publisher: コネット
• [Book] 臨床リウマチ (2013)
  • Author(s): 蛯名 耕介
  • Total Pages: 6
  • Publisher: 日本臨床リウマチ学会
• [Book] 臨床リウマチ (2013)
  • Author(s): 関節リウマチにおける骨粗鬆症とその治療
  • Total Pages: 6
  • Publisher: 日本臨床リウマチ学会