Development of cartilage cells induction method and the establishment of the system to evaluate the effect of novel therapeutic drugs on skeletal dysplasia by using iPS cells

• Project/Area Number: 25461384
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Endocrinology
• Research Institution: Kyoto University
• Principal Investigator: Miura Masako 京都大学, 医学(系)研究科(研究院), 講師 (80437235)
• Co-Investigator(Renkei-kenkyūsha): YASODA Akihiro 京都大学, 医学研究科, 講師 (50378642)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000); Fiscal Year 2015: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2013: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 内分泌学 / CNP / 骨代謝 / 低身長 / iPS細胞 / 軟骨 / 軟骨無形成症 / ナトリウム利尿ペプチド

Outline of Final Research Achievements

In this study, we have tried to establish the system to evaluate the effect of novel therapeutic drugs on skeletal dysplasia, such as achondroplasia, by using iPS cells. Achondroplasia chondrocyte proliferation, differentiation and matrix production is suppressed by the constitutive activation of FGFR3. Then, we performed the cartilage cells induction method to achondroplasia-derived iPS cells. In the process, we did assessment of the effectiveness of CNP by adding CNP. Comparing the CNP added group and the non-addition group showed a certain efficacy in the expression of genes associated with cartilage differentiation. We will keep trying to investigate the effects of CNP on the iPS cells derived from achondroplasia patient.

Research Products

• [Journal Article] The local CNP/GC-B system in the growth plate is responsible for physiological endochondral bone growth. (2015)
  • Author(s): Nakao, K., Osawa, K., Yasoda, A., Yamanaka, S., Fujii, T., Kondo, E., Koyama, N., Kanamoto, N., Miura, M., Kuwahara, K., Akiyama, H., Bessho, K., and Nakao, K..
  • Journal Title: Scientific Reports Volume: 5 Issue: 1 Pages: 1-11
  • DOI: 10.1038/srep10554
  • NAID: 120007100129
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Increased bone turnover and possible accelerated fracture healing in a murine model with an increased circulating C-type natriuretic peptide (2015)
  • Author(s): Eri Kondo, Akihiro Yasoda, Toshihito Fujii, Kazumasa Nakao, Yui Yamashita, Yoriko Ueda-Sakane, Naotetsu Kanamoto, Masako Miura, Hiroshi Arai, Masashi Mukoyama, Nobuya Inagaki and Kazuwa Nakao
  • Journal Title: Endocrinology Volume: 156 Issue: 7 Pages: 2518-2529
  • DOI: 10.1210/en.2014-1801
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Hayakawa, N., Nakamoto, Y., Kurihara, K., Yasoda, A., Kanamoto, N., Miura, M., Inagaki, N., Togashi, K. (2015)
  • Author(s): A comparison between 11C-methionine PET/CT and MIBI SPECT/CT for localization of parathyroid adenomas/hyperplasia
  • Journal Title: Nuclear Medicine Communications Volume: 36 Issue: 1 Pages: 53-59
  • DOI: 10.1097/mnm.0000000000000216
  • Peer Reviewed
• [Journal Article] Role of endogenous ACTH on circadian aldosterone rhythm in patients with primary aldosteronism (2014)
  • Author(s): Sonoyama, T., Sone, M. , Tamura, N., Honda, K., Taura, D., Kojima, K., Fukuda, Y., Kanamoto, N., Miura, M., Yasoda, A., Arai, H., Itoh, H., Nakao, K
  • Journal Title: Endocrine Connections Volume: 3 Issue: 4 Pages: 173-179
  • DOI: 10.1530/ec-14-0086
  • Peer Reviewed / Open Access
• [Journal Article] Adrenal reserve function after unilateral adrenalectomy in patients with primary aldosteronism. (2013)
  • Author(s): Honda K, Sone M, Tamura N, Sonoyama T, Taura D, Kojima K, Fukuda Y, Tanaka S, Yasuno S, Fujii T, Kinoshita H, Ariyasu H, Kanamoto N, Miura M, Yasoda A, Arai H, Ueshima K, Nakao K.
  • Journal Title: J Hypertens Volume: 31 Issue: 10 Pages: 2010-7
  • DOI: 10.1097/hjh.0b013e3283635789
  • Peer Reviewed
• [Presentation] C型ナトリウム利尿ペプチドによる、軟骨無形成症の顎顔面形態異常に対する新規治療法の開発 (2015)
  • Author(s): 山中茂樹, 八十田明宏, 中尾一祐, 小山典昭, 藤井寿人, 近藤絵里, 三浦晶子, 稲垣暢也, 中尾 一和, 別所和久
  • Organizer: 日本内分泌学会
  • Place of Presentation: 東京都 千代田区
  • Year and Date: 2015-04-23 – 2015-04-25
• [Presentation] デノスマブ投与による血清カルシウム値の変動に関する検討 (2015)
  • Author(s): 三浦晶子, 松尾奈緒美, 金丸良徳, 早川尚雅, 堀井和子, 土居健太郎, 稲垣暢也
  • Organizer: 日本内分泌学会
  • Place of Presentation: 東京
  • Year and Date: 2015-04-23
• [Presentation] C型ナトリウム利尿ペプチドによる, 軟骨無形成症の顎顔面形態異常に対する新規治療法の開発 (2015)
  • Author(s): 山中茂樹, 中尾一祐, 八十田明宏, 小山典昭, 藤井寿人, 近藤絵里, 三浦晶子, 稲垣暢也, 中尾一和, 別所和久
  • Organizer: 日本内分泌学会
  • Place of Presentation: 東京
  • Year and Date: 2015-04-23
• [Presentation] 原発性アルドステロン症患者の血漿アルドステロン濃度への内因性ACTHの影響 (2015)
  • Author(s): 園山拓洋, 曽根正勝, 田村尚久, 本田恭子, 田浦大輔, 小嶋勝利, 福田賢英, 金本巨哲, 三浦晶子, 八十田明宏, 荒井宏司, 伊藤裕, 中尾一和
  • Organizer: 日本内分泌学会
  • Place of Presentation: 東京
  • Year and Date: 2015-04-23
• [Presentation] 副腎静脈サンプリングにおけるACTH負荷の意義についての検討 (2015)
  • Author(s): 福田賢英, 曽根正勝, 田浦大輔, 小嶋勝利, 本田恭子, 藤井寿人, 金本巨哲, 三浦晶子, 八十田明宏, 稲垣暢也
  • Organizer: 日本内分泌学会
  • Place of Presentation: 東京
  • Year and Date: 2015-04-23
• [Presentation] CNP/GC-B 系は局所因子として内軟骨骨化を促進する (2014)
  • Author(s): 中尾一祐, 八十田明宏, 大澤賢次, 山中茂樹, 小山典昭,近藤絵里, 藤井寿人, 三浦晶子, 稲 垣暢也, 別所和久,中尾一和
  • Organizer: 骨代謝学会
  • Place of Presentation: 大阪市
  • Year and Date: 2014-07-24 – 2014-07-26
• [Presentation] ヒトiPS細胞から軟骨細胞への分化誘導過程におけるCNPの作用に関する検討 (2014)
  • Author(s): 三浦晶子、小山典昭、中尾一祐、上田依利子、山下唯、近藤絵里、藤井寿人、金本巨哲、曽根正勝、八十田明宏、荒井宏司、別所和久、稲垣暢也、中尾一和
  • Organizer: 第87回日本内分泌学会学術総会
  • Place of Presentation: 福岡国際会議場
• [Presentation] ヒトiPS細胞から軟骨細胞への分化誘導過程におけるCNPの作用に関する検討 (2014)
  • Author(s): 小山典昭、三浦晶子、中尾一祐、上田依利子、山下唯、近藤絵里、藤井寿人、磯部悠、池野正幸、山中茂樹、金本巨哲、曽根正勝、八十田明宏、荒井宏司、別所和久、稲垣暢也、中尾一和
  • Organizer: 第13回日本再生医療学会
  • Place of Presentation: 国立京都国際会議場
• [Presentation] 乳歯幹細胞の特性と再生医療への応用 (2014)
  • Author(s): 山座孝義、三浦晶子
  • Organizer: 第13回日本再生医療学会
  • Place of Presentation: 国立京都国際会議場
  • Invited
• [Presentation] The development of culture method for chondrogenic differentiation of human iPS cells. (2013)
  • Author(s): Koyama N, Miura M, Nakao K, Kondo E, Fujii T, Kanamoto N, Yasoda A, Arai H, Bessho K, Nakao K.
  • Organizer: 2nd Joint Meeting of the International Bone and Mineral Society and The Japanese Society for Bone and Mineral Reseach
  • Place of Presentation: Kobe Convention Center
• [Presentation] The C-type Natriuretic Peptide(CNP)/Guanylyl Cyclase-B(GC-B) system in growth plate promotes endochondral bone growth in an autocrine/paracrine manner. (2013)
  • Author(s): Nakao K, Yasoda A, Osawa K, Koyama N, Kondo E, Fujii T, Miura M, Akiyama H, Bessho K, Nakao K.
  • Organizer: 2nd Joint Meeting of the International Bone and Mineral Society and The Japanese Society for Bone and Mineral Reseach
  • Place of Presentation: Kobe Convention Center
• [Presentation] The role of C-type Natriuretic Peptide(CNP) in mouse fracture healing. (2013)
  • Author(s): Kondo E, Yasoda A, Fujii T, Miura M, Nakao K.
  • Organizer: 2nd Joint Meeting of the International Bone and Mineral Society and The Japanese Society for Bone and Mineral Reseach
  • Place of Presentation: Kobe Convention Center
• [Presentation] Generation and characterization of C-type Natriuretic Peptide(CNP) knockout rats using zinc finger nucleases. (2013)
  • Author(s): Fujii T, Yasoda A, Takizawa A, Kondo E, Nakao K, Miura M, Mashimo T, Serikawa T, Nakao K.
  • Organizer: 2nd Joint Meeting of the International Bone and Mineral Society and The Japanese Society for Bone and Mineral Reseach
  • Place of Presentation: Kobe Convention Center
• [Presentation] 乳歯幹細胞の樹立と臨床応用の可能性 (2013)
  • Author(s): 三浦晶子
  • Organizer: 第34回日本炎症・再生医学会
  • Place of Presentation: 国立京都国際会議場
  • Invited
• [Presentation] Zinc Finger Nuclease Technologyを用いたC型ナトリウム利尿ペプチドノックアウトラットの作製 (2013)
  • Author(s): 藤井寿人、八十田明宏、近藤絵里、有安宏之、金本巨哲、曽根正勝、三浦晶子、荒井宏司、中尾一和
  • Organizer: 第86回日本内分泌学会学術総会
  • Place of Presentation: 仙台国際センター
• [Presentation] C型ナトリウム利尿ペプチド（CNP）の顎顔面形態における影響および顎変形症に対する臨床応用の可能性 –遺伝子改変マウスを用いた解析－ (2013)
  • Author(s): 中尾一祐、八十田明宏、小山典昭、近藤絵里、藤井寿人、三浦晶子、別所和久、中尾一和
  • Organizer: 第86回日本内分泌学会学術総会
  • Place of Presentation: 仙台国際センター
• [Presentation] C型ナトリウム利尿ペプチド（CNP）のマウス骨折治癒における役割の解明 (2013)
  • Author(s): 近藤絵里、八十田明宏、藤井寿人、三浦晶子、中尾一和
  • Organizer: 第31回日本骨代謝学会学術集会
  • Place of Presentation: 神戸コンベンションセンター