Novel action of melanocyte-stimulating hormone on bone: Analysis using fish scales with a high regeneration ability

• Project/Area Number: 16K07871
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Aquatic life science
• Research Institution: Kanazawa University
• Principal Investigator: Suzuki Nobuo 金沢大学, 環日本海域環境研究センター, 教授 (60242476)
• Co-Investigator(Kenkyū-buntansha): 高橋 明義 北里大学, 海洋生命科学部, 教授 (10183849) ; 鈴木 徹 東北大学, 農学研究科, 教授 (70344330)
• Research Collaborator: Hattori Atsuhiko 東京医科歯科大学, 教養部, 教授 (70183910)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2018: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000); Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2016: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
• Keywords: MSH / 骨代謝 / カルシトニン / 円鱗 / 櫛鱗 / ヒラメ / キンギョ / 受容体 / カルシウム / 次世代シークエンス解析 / 骨形成マーカー / 破骨細胞マーカー / 時計遺伝子 / ウロコ / 骨芽細胞 / 破骨細胞 / RANKL / ホルモン / カルシウム代謝

Outline of Final Research Achievements

The purpose of this study is to analyze the novel action of melanocyte-stimulating hormone (MSH) on bone metabolism using fish scales as a bone model. In this study, we analyzed the effects of MSH on bone metabolism in vivo and in vitro using regenerating scales and demonstrated that MSH promotes osteoclastic and osteoblastic activity. In addition, we found that MSH promotes the secretion of calcitonin, which is involved in calcium metabolism. Furthermore, next-generation sequencing analyses were performed to investigate the differentiation mechanism from cycloid scales to ctenoid scales. As a result, it was possible to clarify one of the regulatory mechanisms of bone metabolism related genes in the formation of ctenoid scales.

Academic Significance and Societal Importance of the Research Achievements

本研究により、MSHの骨に対する新規作用を解析することができ、MSHが破骨細胞及び骨芽細胞を活性化し、骨吸収抑制ホルモンであるカルシトニンの分泌を促すことも判明した。さらにヒラメを用いて、円鱗から櫛鱗への分化機構のメカニズムの一端も解析できた。
ヒラメは水産養殖の上で重要な魚種であり、各県の水産試験場では種苗生産を行っている。陸上の養殖時に無眼側の黒化が生じやすく、黒化が起きたヒラメは商業上の価値は低い。したがって、本研究は、無眼側の黒化機構の解明にも貢献できる。

Research Products

• [Int'l Joint Research] Prince of Songkla University(タイ)
• [Int'l Joint Research] DDU Gorakhpur University(インド)
• [Int'l Joint Research] D.D.U. Gorakhpur University(インド)
• [Int'l Joint Research] Can Tho University/Center of Application and Information(ベトナム)
• [Journal Article] α-Melanocyte-stimulating hormone directly increases the plasma calcitonin level and involves calcium metabolism in goldfish (2018)
  • Author(s): Ikari Takahiro、Kobayashi Yuki、Kitani Yoichiro、Sekiguchi Toshio、Endo Masato、Kambegawa Akira、Asahina Kiyoshi、Hattori Atsuhiko、Tabuchi Yoshiaki、Amornsakun Thumronk、Mizusawa Kanta、Takahashi Akiyoshi、Suzuki Nobuo
  • Journal Title: International Aquatic Research Volume: 10 Issue: 3 Pages: 283-292
  • DOI: 10.1007/s40071-018-0206-5
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Molecular characterization of putative calcitonin gene-related peptide receptors and expression of calcitonin gene-related peptide and its receptor in the early development of flounder, Paralichthys olivaceus. (2018)
  • Author(s): Sekiguchi, T., Suzuki, T., Kurokawa, T., Amornsakun, T., Hai, T.N., Srivastav, A.K. and Suzuki, N.
  • Journal Title: International Journal of Zoological Investigations Volume: 4 Pages: 107-116
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Identification of Sox10-positive cells at the dorsal fin base of juvenile flounder that are correlated with blind-side skin ectopic pigmentation (2018)
  • Author(s): Togawa Mai、Endo Yuna、Suzuki Nobuo、Yokoi Hayato、Suzuki Tohru
  • Journal Title: Journal of Experimental Zoology Part B: Molecular and Developmental Evolution Volume: 330 Issue: 8 Pages: 427-437
  • DOI: 10.1002/jez.b.22842
  • Peer Reviewed
• [Journal Article] a-melanocyte-stimulating hormone promotes the bone resorption resulting from increased osteoblastic and osteoclastic activities in goldfish. (2018)
  • Author(s): Ishizu, H., Sekiguchi, T., Ikari, T.,, Kitamura, K., Kitani, Y., Endo, M., Urata, M., Kinoshita, Y., Hattori, A., Srivastav, A.K., Mishima, H., Mizusawa, K., Takahashi, A. and Suzuki, N.
  • Journal Title: Gen. Comp. Endocrinol. Volume: 262 Pages: 99-105
  • DOI: 10.1016/j.ygcen.2018.03.020
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Calcitonin-typical suppression of osteoclastic activity by amphioxus calcitonin superfamily peptides and insights into the evolutionary conservation and diversity of their structures. (2017)
  • Author(s): Sekiguchi, T., Shiraishi, A., Satake, H., Kuwasako, K., Takahashi, H., Sato, M., Urata, M., Wada, S., Endo, M., Ikari, T., Hattori, A., Srivastav, A.K. and Suzuki, N.
  • Journal Title: Gen. Comp. Endocrinol. Volume: 246 Pages: 294-300
  • DOI: 10.1016/j.ygcen.2017.01.004
  • NAID: 120005973614
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Sodium fluoride influences calcium metabolism resulting from the suppression of osteoclasts in the scales of nibbler fish Girella punctata (2017)
  • Author(s): Masayuki Sato, Koji Yachiguchi, Keiichi Motohashi, Yukio Yaguchi, Yoshiaki Tabuchi, Yoichiro Kitani,, Takahiro Ikari, Shouzo Ogiso, Toshio Sekiguchi, Tran Ngoc Hai, Do Thi Thanh Huong, Nguyen Viet Hoang, Makoto Urata, Hiroyuki Mishima, Atsuhiko Hattori, Nobuo Suzuki
  • Journal Title: Fish Sci Volume: ー Issue: 4 Pages: 543-550
  • DOI: 10.1007/s12562-017-1086-0
  • NAID: 120006306228
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Sardine procalcitonin amino-terminal cleavage peptide has a different action from calcitonin and promotes osteoblastic activity in the scales of goldfish. (2017)
  • Author(s): Kase, Y., Ikari, T., Sekiguchi, T., Sato, M., Ogiso, S., Kawada, T., Matsubara, S., Satake, H., Sasayama, Y., Endo, M., Kitamura, K., Hattori, A., Watanabe, T.X., Maruyama, Y., Watanabe, Y., Funahashi, H., Kambegawa, A. and Suzuki, N.
  • Journal Title: Comp. Biochem. Physiol. Part A Volume: 211 Pages: 73-83
  • DOI: 10.1016/j.cbpa.2017.06.007
  • NAID: 120006336026
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Benz[a]anthracene decreases plasma calcium levels resulting from influence of scale osteoclastic and osteoblastic activities in goldfish. (2017)
  • Author(s): Suzuki, N., Nakano, J., Kawabe, K., Toriba, A., Hayakawa, K., Tang, N, Sekiguchi, T., Tabuchi, Y., Ikegame, M., Shimizu, N., Mishima, H., Hattori, A., Srivastav, A.K. and Kitani, Y.
  • Journal Title: Int. J. Zool. Inv. Volume: 3 Pages: 72-81
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] キンギョ鱗における多核破骨細胞形成に関する形態学的研究：筋肉内自家移植鱗を用いた解析 (2017)
  • Author(s): 池亀美華、村埜淑恵、國定勇希、服部淳彦、鈴木信雄、山本敏男
  • Journal Title: 岡山歯学会雑誌 Volume: 35 Pages: 37-42
  • Peer Reviewed
• [Journal Article] Seawater polluted with highly concentrated polycyclic aromatic hydrocarbons suppresses osteoblastic activity in the scales of goldfish, Carassius auratus. (2016)
  • Author(s): Suzuki, N., Sato, M., Nassar, F. H., Abdel-gawad, F. Kh., Bassem, S.M., Yachiguchi, K., Tabuchi, Y., Endo, M., Sekiguchi, T., Urata, M., Hattori, A., Mishima, H., Shimasaki, Y., Oshima, Y., Hong, C.-S., Makino, F., Tang, N., Toriba, A. and Hayakawa, K
  • Journal Title: Zool. Sci. Volume: 33 Issue: 4 Pages: 407-413
  • DOI: 10.2108/zs150211
  • NAID: 120005851366
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] odium fluoride induces hypercalcemia resulting from the upregulation of both osteoblastic and osteoclastic activities in goldfish, Carassius auratus. (2016)
  • Author(s): Sato, M., Hanmoto, T., Yachiguchi, K., Tabuchi, Y., Kondo, T., Endo, M., Kitani, Y., Sekiguchi, T., Urata, M., Hai, T.N., Srivastav, A.K., Mishima, H., Hattori, A. and Suzuki, N.
  • Journal Title: Comp. Biochem. Physiol. Part C. Volume: 189 Pages: 54-66
  • DOI: 10.1016/j.cbpc.2016.07.006
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Fish scale is a suitable model for analyzing determinants of skeletal fragility in type 2 diabetes. (2016)
  • Author(s): Suzuki N, Kitamura K, Hattori A
  • Journal Title: Endocrine Volume: 54 Issue: 3 Pages: 575-577
  • DOI: 10.1007/s12020-016-1153-9
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Presentation] Alpha-melanocyte-stimulating hormone functions to fish calcium metabolism. (2019)
  • Author(s): Suzuki, N., Ikari, T., Kobayashi, Y., Mizusawa, K., Takahashi, A., Kitani, Y., Sekiguchi, T., Endo, M., Kambegawa, A., Asahina, K., Tabuchi, Y., Amornsakun, T., Hattori A.
  • Organizer: International Symposium “Research Frontiers of Transboundary Pollution”, Kanazawa University
  • Int'l Joint Research
• [Presentation] α-MSHは血漿カルシトニン濃度を上昇させてカルシウム代謝に関与する． (2018)
  • Author(s): 鈴木信雄，五十里雄大，小林勇喜，水澤寛太，高橋明義，木谷洋一郎，関口俊男，遠藤雅人，神戸川明，朝比奈潔，田渕圭章，Amornsakun T，服部淳彦
  • Organizer: 第43回日本比較内分泌学会大会
• [Presentation] Teleost scale is an functional calcium reservoir and has an important physiological role in calcium metabolism. (2018)
  • Author(s): Suzuki, N.
  • Organizer: 8th International Fisheries Symposium 2018
  • Int'l Joint Research / Invited
• [Presentation] Alpha-melanocyte-stimulating hormone increases plasma calcitonin level and is involved in fish calcium metabolism. (2018)
  • Author(s): Suzuki, N., Ikari, T., Kobayashi, Y., Mizusawa, K., Takahashi, A., Kitani, Y., Sekiguchi, T., Endo, M., Kambegawa, A., Asahina, K., Tabuchi, Y., Amornsakun, T., Hattori A.
  • Organizer: Joint Symposium between Kanazawa University and Prince of Songkla University on Recent Advances in Marine Science, Aquaculture and Food Technology, Kanazawa University
  • Int'l Joint Research
• [Presentation] α-melanocyte-stimulating hormone functions to calcium metabolism in goldfish. (2018)
  • Author(s): Ishizu, H., Sekiguchi, T., Ikari, T., Kitamura, K., Kitani, Y., Endo, M., Urata, M., Hattori, A., Mizusawa, K., Takahashi, A. and Suzuki, N.
  • Organizer: International Symposium “Environmental researches in northern Japan Sea and related regions: Renewed horizon of Japan-Russia scientific partnership”
  • Int'l Joint Research
• [Presentation] 魚類の骨代謝に対する黒色素胞刺激ホルモンの影響：in vivo及びin vitroによる解析． (2018)
  • Author(s): 鈴木信雄，石津偉統，木谷洋一郎，五十里雄大，関口俊男，北村敬一郎，遠藤雅人，服部淳彦，水澤寛太，高橋明義
  • Organizer: 平成30年度日本水産学会春季大会
• [Presentation] 魚類の骨代謝に対する黒色素胞刺激ホルモンの影響 (2017)
  • Author(s): 鈴木信雄、木谷洋一郎、五十里雄大、石津偉統、小木曽正造、関口俊男、服部淳彦、高橋明義
  • Organizer: 平成29年度日本水産学会春季大会
  • Place of Presentation: 東京海洋大学
  • Year and Date: 2017-03-26
• [Presentation] 黒色素胞刺激ホルモンはキンギョの骨芽細胞及び破骨細胞を活性化する． (2017)
  • Author(s): 石津偉統，五十里雄大，木谷洋一郎，小木曽正造，関口俊男，服部淳彦，高橋明義，鈴木信雄
  • Organizer: 日本動物学会第88 回富山大会
• [Presentation] 骨代謝―メラトニンの骨代謝に対する作用：ウロコを骨モデルとして用いた解析 (2017)
  • Author(s): 鈴木信雄
  • Organizer: 日本動物学会第88 回富山大会
  • Invited
• [Presentation] 金沢大学が目指すアクアバイオの研究 (2017)
  • Author(s): 鈴木信雄
  • Organizer: 日本海イノベーション会議
  • Invited
• [Presentation] Effects of α-melanocyte-stimulating hormone on osteoblasts and osteoclasts in the regenerating scales of goldfish. (2017)
  • Author(s): Ishizu, H., Sekiguchi, T., Ikari, T., Kitamura, K., Kitani, Y., Endo, M., Urata, M., Hattori, A., Mizusawa, K., Takahashi, A. and Suzuki, N.
  • Organizer: 3rd International Symposium “International Collaboration Research Base for Reaction of Atmosphere-Marine-Ecosystem Caused by Aerosol”
  • Int'l Joint Research
• [Presentation] Introduction of fish research in Kanazawa University. (2016)
  • Author(s): Suzuki, N.
  • Organizer: KU-CTU Joint Symposium: Environment, Aquaculture and Fisheries.
  • Place of Presentation: Can Tho University, Vietnam,
  • Year and Date: 2016-12-12
  • Int'l Joint Research / Invited
• [Presentation] 繁殖後期のキンギョにおける血漿カルシウム濃度の低下と鱗で産生されるメラトニンとの関連 (2016)
  • Author(s): 松岡里沙，丸山雄介，鈴木信雄，服部淳彦
  • Organizer: 第 41回日本比較内分泌学会大及びシンポジウム
  • Place of Presentation: 北里大学
  • Year and Date: 2016-12-09