The regulation of bone metabolism by amino acid

• Project/Area Number: 23689004
• Research Category: Grant-in-Aid for Young Scientists (A)
• Allocation Type: Single-year Grants
• Research Field: Biological pharmacy
• Research Institution: Kanazawa University
• Principal Investigator: HINOI Eiichi 金沢大学, 薬学系, 准教授 (70360865)
• Project Period (FY): 2011-04-01 – 2014-03-31
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥27,300,000 (Direct Cost: ¥21,000,000、Indirect Cost: ¥6,300,000); Fiscal Year 2013: ¥7,020,000 (Direct Cost: ¥5,400,000、Indirect Cost: ¥1,620,000); Fiscal Year 2012: ¥10,530,000 (Direct Cost: ¥8,100,000、Indirect Cost: ¥2,430,000); Fiscal Year 2011: ¥9,750,000 (Direct Cost: ¥7,500,000、Indirect Cost: ¥2,250,000)
• Keywords: 骨代謝 / 骨芽細胞 / 破骨細胞 / 遺伝子欠損マウス / アミノ酸 / 骨粗鬆症

Research Abstract

Although amino acid transporters are indispensable for a variety of cellular events in eukaryotic cells, little attention has been paid to their functional role in bone modeling and remodeling so far. Here, we have attempted to demonstrate the possible involvement of a system A amino acid transporter Slc38a1 in the regulation of osteoblastogenesis and osteoclastogenesis in vivo. To that end, cell-specific (osteoblast and osteoclast) knockout mice were generated. In vertebrae of those knockout mice, no marked change was seen in bone volume over tissue volume, osteoblastic parameter and osteoclastic parameter compared with wild-type (WT) mice by bone histomorphometric analyses. Moreover, ovariectomy resulted in a marked reduction of vertebrae bone volume in both WT mice and osteoblast-specific Slc38a1 knockout mice.

Research Products

• [Journal Article] An analysis of skeletal development in osteoblast- and chondrocyte-specific Runx2 knockout mice (2013)
  • Author(s): Takeshi Takarada, Eiichi Hinoi, Ryota Nakazato, Hiroki Ochi, Cheng Xu, Azusa Tsuchikane, Shu Takeda, Gerard Karsenty, Takaya Abe, Hiroshi Kiyonari, and Yukio Yoneda
  • Journal Title: J. Bone Miner. Res Volume: 未定 Issue: 10 Pages: 2064-9
  • DOI: 10.1002/jbmr.1945
  • Peer Reviewed
• [Journal Article] Negative correlation between Per1 and Sox6 expression during chondrogenic differentiation in pre-chondrocytic ATDC5 cells (2013)
  • Author(s): Le, N.Q., Binh, N.T., Takarada, T., Takarada-Iemata, M., Hinoi, E. and Yoneda, Y
  • Journal Title: J. Pharmacol. Sci Volume: 122 Pages: 318-25
  • NAID: 10031196205
  • URL: http://www.ncbi.nlm.nih.gov/pubmed/23883486
  • Peer Reviewed
• [Journal Article] Negative correlation between Per1 and Sox6 expression during chondrogenic differentiation in pre-chondrocytic ATDC5 cells. (2013)
  • Author(s): Le NQ, Binh NT, Takarada T, Takarada-Iemata M, Hinoi E, Yoneda Y.
  • Journal Title: J Pharmacol Sci. Volume: 122(4) Pages: 318-325
  • NAID: 10031196205
  • Peer Reviewed
• [Journal Article] The transcription factor paired box-5 promotes osteoblastogenesis through direct induction of Osterix and Osteocalcin (2012)
  • Author(s): Hinoi, E., Nakatani, E., Yamamoto, T., Iezaki, T., Takahata, Y., Fujita, H., Ishiura, R., Takamori, M. and Yoneda, Y
  • Journal Title: J. Bone Miner. Res Volume: 27 Issue: 12 Pages: 2526-34
  • DOI: 10.1002/jbmr.1708
  • Peer Reviewed
• [Journal Article] Positive regulation of osteoclastic differentiation by growth differentiation factor-15 up-regulated in osteocytic cells under hypoxia (2012)
  • Author(s): Eiichi Hinoi, Hiroki Ochi, Takeshi Takarada, Eri Nakatani, Takashi Iezaki, Hiroko Nakajima, Hiroyuki Fujita, Yoshifumi Takahata, Shinya Hidano, Takashi Kobayashi, Shu Takeda, Yukio Yoneda
  • Journal Title: J Bone Miner Res Volume: 4 Issue: 4 Pages: 938-949
  • DOI: 10.1002/jbmr.1538
  • Peer Reviewed
• [Journal Article] PossiblePossible involvement of glutamatergic signaling machineries in pathophysiology of rheumatoid arthritis (2011)
  • Author(s): Hinoi, E. and Yoneda, Y
  • Journal Title: J. Pharmacol. Sci Volume: 116 Pages: 248-56
  • URL: http://www.ncbi.nlm.nih.gov/pubmed/21666346
  • Peer Reviewed
• [Journal Article] Possible involvement of glutamatergic signaling machineries in pathophysiology of rheumatoid arthritis (2011)
  • Author(s): Hinoi, E.
  • Journal Title: J Pharmacol Sci Volume: 116 Pages: 248-256
  • NAID: 10029894955
  • Peer Reviewed
• [Presentation] Growth differentiation factor-15を介した骨細胞による破骨細胞活性化調節 (2014)
  • Author(s): 檜井栄一
  • Organizer: 日本薬学会第134年会
  • Place of Presentation: 熊本市水道町鶴屋7Fカーネーションサロン(熊本県)
  • Year and Date: 2014-03-29
• [Presentation] 低酸素誘導性骨細胞由来因子GDF15による破骨細胞機能調節機構、第15回骨発生 (2012)
  • Author(s): 檜井栄一
  • Organizer: 再生研究会
  • Place of Presentation: 慶応大学(東京都)
  • Year and Date: 2012-11-10
• [Presentation] 骨格系細胞群のシグナル応答性解明研究 (2012)
  • Author(s): 檜井栄一
  • Organizer: 第85回日本薬理学会年会
  • Place of Presentation: 京都国際会議場(京都府)
  • Year and Date: 2012-03-15
• [Presentation] 骨格系細胞群のシグナル応答性解明研究 (2012)
  • Author(s): 檜井栄一
  • Organizer: 第85回日本薬理学会年会
  • Place of Presentation: 京都国際会議場(京都)(招待講演)
  • Year and Date: 2012-03-15
• [Presentation] Growth differentiation factor-15を介した骨細胞 による破骨細胞活性化調節
  • Author(s): 檜井栄一
  • Organizer: 日本薬学会第134年会
  • Place of Presentation: 熊本市水道町鶴屋7Fカーネーションさろん（熊本県）
  • Invited
• [Presentation] 低酸素誘導性骨細胞由来因子GDF15による破骨細胞機能調節機構
  • Author(s): 檜井栄一
  • Organizer: 第15回骨発生・再生研究会
  • Place of Presentation: 慶應大学(東京都）
  • Invited
• [Remarks]
  • URL: http://www.p.kanazawa-u.ac.jp/~yakubutu/index.html
• [Remarks]
  • URL: http://www.p.kanazawa-u.ac.jp/~yakubutu/index.html
• [Patent(Industrial Property Rights)] 破骨細胞が関与する疾患の予防剤及び /又は治療剤 (2011)
  • Inventor(s): 米田幸雄、檜井栄一、山本朋未、家崎高志、石浦遼
  • Industrial Property Rights Holder: 金沢大学
  • Industrial Property Rights Type: 特許
  • Industrial Property Number: 2011-238455
  • Filing Date: 2011-10-31
  • Overseas
• [Patent(Industrial Property Rights)] 破骨細胞が関与する疾患の予防剤及び/又は治療剤 (2011)
  • Inventor(s): 檜井栄一, 他
  • Industrial Property Rights Holder: 金沢大学
  • Industrial Property Number: 2011-238455
  • Filing Date: 2011-10-31