Molecular insights of the crosstalk between locomotive and metabolic syndromes

• Project/Area Number: 25462380
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Orthopaedic surgery
• Research Institution: Saitama Medical University
• Principal Investigator: Matsumoto Masahito 埼玉医科大学, 医学部, 講師 (90321819)
• Co-Investigator(Kenkyū-buntansha): NAKACHI YUTAKA 埼玉医科大, 医学部, 助教 (10522097) ; SUDA TATSUO 埼玉医科大, 医学部, 客員教授 (90014034)
• Co-Investigator(Renkei-kenkyūsha): SUGAHARA IZUMI 埼玉医科大, 医学部, 研究員 (10633000) ; OKAZAKI YASUSHI 埼玉医科大, 医学部, 教授 (80280733) ; YASUNAMI YOICHI 福岡大学, 医学部, 教授 (00166521) ; SATO TSUYOSHI 福岡大学, 医学部, 准教授 (60406494)
• 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: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2014: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2013: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
• Keywords: 骨代謝 / 糖代謝 / エピジェネティック / 転写因子 / 破骨細胞 / 骨芽細胞 / ロコモティブ / エピジェネティクス / Pax6 / 分化 / 遺伝子調節

Outline of Final Research Achievements

Elucidation of molecular insights underlying the crosstalk between metabolic and rocomotive syndromes is important since it is clearly shown that most of diabetic patients accompanies with vulnerability of their bones, resulting from the bone destruction. Herein we found several evidence as below. First, a transcription factor Pax6, is critical for pancreatic endocrine cell differentiation, attenuates the differentiation of osteoclasts. Second, a neuropeptide CRF suppresses apoptosis of pancreatic beta cells treated with inflammatory cytokines. Third, endothelial cell-derived Netrin-4 inhibits osteoclatogenesis. Lastly, the gene expression of a limited sets of cell cycle regulators mediated by DNA methylation might contribute to osteoblast differentiation. Control of Pax6 transcription and epigenetic functionality therefore may lead to explore and identify novel therapeutic targets upon unknown crosstalk essential for metabolic syndromes both of bone and glucose.

Research Products

• [Journal Article] Involvement of skeletal fragility by teriparatide in adult osteoporosis patients: a novel mechanostat-based hypothesis for bone quality. (2015)
  • Author(s): Sugiyama T, Torio T, Sato T, Matsumoto M, Kim YT, Oda H.
  • Journal Title: Frontiers in Endocrinol. Volume: 6 Pages: 6-6
  • DOI: 10.3389/fendo.2015.00006
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Donepezil prevents RANK-induced boneloss via inhibitionofosteoclast differentiation by downregulating acetylcholinesterase. (2015)
  • Author(s): Sato T, Enoki Y, Sakamoto Y, Yokota K, Okubo M, Matsumoto M, Hayashi N, Usui M, Kokabu S, Mimura T, Nakazato T, Araki N, Fukuda T, Okazaki Y, Suda T, Takeda S, Yoda T.
  • Journal Title: Heliyon Volume: 1 Issue: 1 Pages: 1-20
  • DOI: 10.1016/j.heliyon.2015.e00013
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] The Paired-box Domain Transcription Factor Pax6 Binds to the Upstream Region of the TRAP Gene Promoter and Suppresses RANKL-induced Osteoclast Differentiation (2013)
  • Author(s): Kogawa M, Hisatake K, Atkins GJ, Findlay DM, Enoki Y, Sato T, Gray PC, Kanesaki-Yatsuka Y, Anerson PH, Wada S, Kato N, Fukuda A, Katayama S, Tsujimoto M, Yoda T, Suda T, Okazaki Y, Matsumoto M
  • Journal Title: J Biol Chem Volume: 288 Issue: 43 Pages: 31299-31312
  • DOI: 10.1074/jbc.m113.461848
  • Peer Reviewed
• [Journal Article] Family with sequence familarity 57, member B (Fam57b), a novel peroxisome proliferator-activated receptor g target gene that regulates adipogenesis through ceramide synthesis. (2013)
  • Author(s): Yamashita-Sugahara Y., Tokuzawa, Y., Nakachi, Y., Knesaki-Yatsuka, Y., Matsumoto, M., Mizuno, Y., Okazaki, Y.
  • Journal Title: J. Biol. Chem. Volume: 288 Issue: 7 Pages: 4522-4537
  • DOI: 10.1074/jbc.m112.440792
  • Peer Reviewed
• [Journal Article] Critical role of p38 MAPK for regeneration of the sciatic nerve following crush injury in vivo (2013)
  • Author(s): Kato, N., Matsumoto, M., Kogawa, M., Atkins, G.J., Findlay, D.M., Fujikawa, T., Oda, H., and Ogata, M.
  • Journal Title: Journal of neuroinflammation Volume: 10 Issue: 1 Pages: 1-1
  • DOI: 10.1186/1742-2094-10-1
  • Peer Reviewed
• [Presentation] Epigenetic control of osteoblast differentiation via DNA methylation (2015)
  • Author(s): Okubo M., Matsumoto M, Mizuno Y, Sato T, Yoda T, Okazaki Y.
  • Organizer: 第38回日本分子生物学会年会
  • Place of Presentation: 神戸国際会議場(兵庫県神戸市)
  • Year and Date: 2015-12-01
• [Presentation] アセチルコリンエステラーゼ阻害剤であるドネペジルは、破骨細胞の形成と機能を強力に抑制し、RANKL誘導性の急速な骨量減少を防止する (2015)
  • Author(s): 佐藤毅、大久保正彦、榎木祐一郎、古株彰一郎、松本征仁、杉山聡宏、依田哲也
  • Organizer: 第33回日本骨代謝学会
  • Place of Presentation: 京王プラザホテル(東京都新宿区)
  • Year and Date: 2015-07-22
• [Presentation] DNAのメチル化を介した骨芽細胞分化のエピジェネティクス制御 (2015)
  • Author(s): 大久保正彦, 松本征仁, 榎木祐一郎, 佐藤毅, 須田立雄, 岡﨑康司, 依田哲也
  • Organizer: 第33回日本骨代謝学会
  • Place of Presentation: 京王プラザホテル(東京都新宿区)
  • Year and Date: 2015-07-22
• [Presentation] 新たな破骨細胞分化抑制因子としてのPax6の機能解析 (2015)
  • Author(s): 大久保正彦, 松本征仁, 甲川昌和, 八塚由紀子, 榎木祐一郎, 佐藤毅, 片山茂裕, 須田立雄, 岡﨑康司, 依田哲也
  • Organizer: 第69回日本口腔科学会学術集会
  • Place of Presentation: 大阪国際会議場(大阪府大阪市)
  • Year and Date: 2015-05-13
• [Presentation] Dual functional roles of Pax6 in the regulation of bone and glucose metabolism Osteoclast Differentiation. (2013)
  • Author(s): Kogawa, M., Hisatake, K., Atkins, G.J., Findlay, D.M., Enoki, Y., Sato, Tsuyoshi, Gray, P, Wada, S., Kato, N., Fukuda, A., Katayama, S., Tsujimoto, M., Yoda, T., Suda, T., Okazaki, Y., and Matsumoto, M.
  • Organizer: ASBMR
  • Place of Presentation: Maryland USA
• [Presentation] Involvement of acetylcholinesterase in osteoclast differentiation. (2013)
  • Author(s): Enoki, Y., Sato, T., Kokabu, S., Okubo, M., Iwata, T., Usui, M., Fukuda, T., Takeda, S, Matsumoto, M., Yoda, T.
  • Organizer: IBMS
  • Place of Presentation: Kobe
• [Presentation] Vascular endothelial cells inhibit osteoclastogenesis by netrin 4 through DSCAM receptor (2013)
  • Author(s): Enoki, Y., Sato, T., Kokabu, S., Okubo, M., Iwata, T., Usui, M., Fukuda, T., Takeda, S, Matsumoto, M., Yoda, T.
  • Organizer: ASBMR
  • Place of Presentation: Maryland USA
• [Presentation] ヒトiPS細胞におけるヘルパー依存型アデノウィルスを用いたInsulin promoter-Venusレポーター細胞の作製とその解析 (2013)
  • Author(s): 菅原泉 松村瞭、佐藤達也、松谷智子、相澤絵美、岩長ゆずる、松本征仁、三谷幸之介、岡崎康司
  • Organizer: 第11回 RCGMシンポジウム
  • Place of Presentation: 埼玉日高市
• [Presentation] Self-limiting system of osteoclast differentiation by the Paired-box Domain Transcription factor Pax6 (2013)
  • Author(s): Masahito Matsumoto, Masakazu Kogawa, Koji Hisatake, Gerald J. Atkins, David M. Findlay, Yuichiro Enoki, Tsuyoshi Sato, Peter C. Gray8, Yukiko Kanesaki-Yatsuka5, Paul H. Anderson9, Seiki Wada2, Naoki Kato4, Aya Fukuda1,7, Shigehiro Katayama, Masafumi Tsujimoto, Tetsuya Yoda, Tatsuo Suda, Yasushi Okazaki
  • Organizer: 第36回日本分子生物学会年会
  • Place of Presentation: 神戸
• [Patent(Industrial Property Rights)] 膵内分泌細胞及びその製造方法、並びに分化転換剤 (2015)
  • Inventor(s): 松本征仁、岡﨑康司、菅原泉
  • Industrial Property Rights Holder: 松本征仁、岡﨑康司、菅原泉
  • Industrial Property Rights Type: 特許
  • Filing Date: 2015-07-03
  • Overseas