Detection of new molecules which induce bone lysis and new bone formation, and analysis of pathophysiology in arthropathy using induced pluripotent stem (iPS) cells

• Project/Area Number: 25461491
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Collagenous pathology/Allergology
• Research Institution: Kurume University
• Principal Investigator: Ida Hiroaki 久留米大学, 医学部, 教授 (60363496)
• Co-Investigator(Kenkyū-buntansha): KAIEDA Shinjiro 久留米大学医学部, 呼吸器・神経・膠原病内科, 講師 (20330798)
• Co-Investigator(Renkei-kenkyūsha): YOSHIURA Koichiro 長崎大学, 医歯薬学総合研究科人類遺伝学, 教授 (00304931) ; SAITO Megumu 京都大学, iPS細胞研究所, 准教授 (90535486)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2013: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: 骨破壊 / 遺伝子 / 関節 / 次世代シークエンサー / iPS細胞 / 次世代

Outline of Final Research Achievements

We performed homozygosity mapping for a consanguineous patient suffered from joint destruction using SNPs GeneChip array compared with a healthy patient brother. We detected 2049 candidate genes in this study. As we could not narrow down the candidate genes in homozygosity mapping, we examined the candidate genes using next generation sequencing. We could detect 10 candidate genes from 11 locuses in this system, and narrow down and confirm 6 missense mutations after Sanger sequencing. Moreover, we confirmed the 5 gene expressions from 6 candidate genes using RT-PCR in both chondrocytes and osteoblasts.To know the role of pathophysiology in this arthropathy, we planned to establish the iPS cells. Several clones of the iPS cells derived from a patient were established in CiRA (Center for iPS Cell Research and Application, Kyoto University). After we received iPS cells from CiRA, we tried to differentiate into chondrocytes, osteoblasts, and osteoclasts.

Research Products

• [Journal Article] Identification of Disease-Promoting HLA Class I and Protective Class II Modifiers in Japanese Patients with Familial Mediterranean Fever. (2015)
  • Author(s): Yasunami M, Nakamura H, Nakamura A, Yazaki M, Kishida D et al.
  • Journal Title: PLoS One Volume: May 14;10(5) Issue: 5 Pages: e0125938-e0125938
  • DOI: 10.1371/journal.pone.0125938
  • NAID: 120007100158
  • Peer Reviewed / Open Access
• [Journal Article] Serum interferon-α is a useful biomarker in patients with anti-melanoma differentiation-associated gene 5 (MDA5) antibody-positive dermatomyositis. (2015)
  • Author(s): Horai Y, Koga T, Fujikawa K, Takatani A, Nishino A, Nakashima Y, Suzuki T, Kawashiri SY, Iwamoto N, Ichinose K, Tamai M, Nakamura H, Ida H, Kakugawa T, Sakamoto N, Ishimatsu Y, Mukae H, Hamaguchi Y, Fujimoto M, Kuwana M, Origuchi T, Kohno S, Kawakami A.
  • Journal Title: Mod Rheumatol. Volume: 25 Issue: 1 Pages: 85-89
  • DOI: 10.3109/14397595.2014.900843
  • Peer Reviewed / Open Access
• [Journal Article] Cutaneous necrotizing vasculitis as a manifestation of familial Mediterranean fever. (2014)
  • Author(s): Komatsu S, Honma M, Igawa S, Tsuji H, Ishida-Yamamoto A, Migita K, Ida H, Iizuka H.
  • Journal Title: J Dermatol. Volume: 41 Issue: 9 Pages: 827-9
  • DOI: 10.1111/1346-8138.12588
  • Peer Reviewed / Open Access
• [Journal Article] Successful treatment of Schnitzler syndrome with cyclosporine. (2014)
  • Author(s): Nakajima K. Takahashi M, Yamamoto M, Takahashi A, Sano S, Kodama H, Arima K, Ida H.
  • Journal Title: Int J Dermatol. Volume: 53 Issue: 7
  • DOI: 10.1111/ijd.12300
  • Peer Reviewed / Open Access
• [Journal Article] Familial Mediterranean Fever: genotype-phenotype correlations in Japanese patients. (2014)
  • Author(s): Migita K, Agematsu K, Yazaki M, Nonaka F, Nakamura A, Toma T, Kishida D,
  • Journal Title: Medicine(Baltimore) Volume: 93 Pages: 158-164
  • Peer Reviewed
• [Journal Article] Successful treatment of Schnitzler syndrome with cyclosporine. (2014)
  • Author(s): Nakajima K, Takahashi M, Yamamoto M, Takahashi A, Sano S, Kodama H, Arima K,
  • Journal Title: Int J Dermatol. Volume: 印刷中
  • Peer Reviewed
• [Journal Article] The contribution of SAA1 polymorphisms to Familial Mediterranean fever susceptibility in the Japanese population. (2013)
  • Author(s): Migita K, Agematsu K, Masumoto J, Ida H, Honda S, Jiuchi Y, Izumi Y, Maeda Y, Uehara R, Nakamura Y, Koga T, Kawakami A, Nakashima M, Fujieda Y, Nonaka F, Eguchi K, Furukawa H, Nakamura T,Nakamura M, Yasunami M.
  • Journal Title: PLoS One Volume: 8
  • NAID: 120006985735
  • Peer Reviewed
• [Presentation] 当科で経験した家族性地中海熱症例の検討 (2015)
  • Author(s): 井田弘明、國武由紀子、吉田直実、若杉大輔、田尻守拡、岡元昌樹、富永正樹、海江田信二郎、右田清志、福田孝昭
  • Organizer: 第59回日本リウマチ学会総会
  • Place of Presentation: 名古屋
  • Year and Date: 2015-04-23
• [Presentation] 教育講演8 自己炎症症候群の診断と治療 (2015)
  • Author(s): 井田弘明
  • Organizer: 第112回日本内科学会
  • Place of Presentation: 京都
  • Year and Date: 2015-04-10
  • Invited
• [Presentation] 当科で経験した家族性地中海熱症例の検討 (2014)
  • Author(s): 井田弘明、國武由紀子、吉田直実、海江田信二郎、右田清志、福田孝昭
  • Organizer: 第48回九州リウマチ学会
  • Place of Presentation: 久留米
  • Year and Date: 2014-09-06 – 2014-09-07
• [Presentation] 炎症性腸疾患を合併したPAPA症候群の一例 (2014)
  • Author(s): 井田弘明、日高由紀子、吉田直実、海江田信二郎、光山慶一、岩本一亜、石丸裕康、藤田久美、熊木恵里、森尾友宏、西小森隆太
  • Organizer: 第35回日本炎症・再生医学会
  • Place of Presentation: 沖縄
  • Year and Date: 2014-07-01 – 2014-07-04
• [Presentation] 教育講演2 Autoinflammatory syndrome (2014)
  • Author(s): 井田弘明
  • Organizer: 第58回日本リウマチ学会総会・学術集会
  • Place of Presentation: 東京
  • Year and Date: 2014-04-24 – 2014-04-26
  • Invited
• [Presentation] プロテアソーム機能不全症における慢性炎症の解析 (2013)
  • Author(s): 井田弘明、海江田信二郎、井手元晶子、吉田直実、本多靖洋、福田孝昭．
  • Organizer: 第57回日本リウマチ学会総会
  • Place of Presentation: 京都
• [Presentation] 自己炎症性骨疾患である肥大性骨関節症の遺伝子検索 (2013)
  • Author(s): 井田弘明、藤川敬太、海江田信二郎、三嶋博之、吉浦孝一郎、右田清志、川上純、福田孝昭．
  • Organizer: 第34回日本炎症・再生医学会
  • Place of Presentation: 京都