Identification of bone derived brain function regulating factor through bone-brain cross talk.

• Project/Area Number: 15K15545
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Orthopaedic surgery
• Research Institution: Tokyo Medical and Dental University
• Principal Investigator: Ochi Hiroki 東京医科歯科大学, 大学院医歯学総合研究科, 助教 (30582283)
• Project Period (FY): 2015-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000); Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2015: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: 骨代謝 / 成長ホルモン / 臓器連関 / 神経 / 臓器間クロストーク

Outline of Final Research Achievements

The purpose of this study was to clarify the regulatory mechanism of the bone derived brain regulating factor. Firstly, we generated the bone specific membrane protein deficient (CKO) mice and analyzed. CKO mice showed dwarfism via low serum GH and IGF-1, and then low bone mass caused by decrease of osteoblast differentiation. Furthermore, matured osteoblast derived factors inhibited the GH expression on a GH3 pituitary cell line. These findings in this study indicates that bone regulates GH secretion in pituitary. We are now trying to clarify the molecular mechanism on the regulation of GH secretion by bone-derived factors.

Research Products

• [Journal Article] Bone Resorption Is Regulated by Circadian Clock in Osteoblasts. (2017)
  • Author(s): Takarada T, Xu C, Ochi H, Nakazato R, Yamada D, Nakamura S, Kodama A, Shimba S, Mieda M, Fukasawa K, Ozaki K, Iezaki T, Fujikawa K, Yoneda Y, Numano R, Hida A, Tei H, Takeda S, Hinoi E.
  • Journal Title: J Bone Miner Res. Volume: 32 Issue: 4 Pages: 872-881
  • DOI: 10.1002/jbmr.3053
  • Peer Reviewed
• [Journal Article] WNK4 is an Adipogenic Factor and Its Deletion Reduces Diet-Induced Obesity in Mice. (2017)
  • Author(s): Takahashi D, Mori T, Sohara E, Tanaka M, Chiga M, Inoue Y, Nomura N, Zeniya M, Ochi H, Takeda S, Suganami T, Rai T, Uchida S.
  • Journal Title: EBioMedicine Volume: 18 Pages: 118-27
  • DOI: 10.1016/j.ebiom.2017.03.011
  • Peer Reviewed / Open Access
• [Journal Article] Pleiotropic Functions of High Fat Diet in the Etiology of Osteoarthritis. (2016)
  • Author(s): Asou Y, Iwata M, Ochi H, Ailixiding M, Aibibula Z, Piao J, Jin G, Hara Y, Okawa A.
  • Journal Title: PLoS One. Volume: 11 Issue: 9 Pages: e0162794-e0162794
  • DOI: 10.1371/journal.pone.0162794
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Circadian Clock Regulates Bone Resorption in Mice. Circadian Clock Regulates Bone Resorption in Mice. (2016)
  • Author(s): Xu C, Ochi H, Fukuda T, Sato S, Sunamura S, Takarada T, Hinoi E, Okawa A, Takeda S.
  • Journal Title: J Bone Miner Res. Volume: - Issue: 7 Pages: 1344-1355
  • DOI: 10.1002/jbmr.2803
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Circadian Clock Regulates Bone Resorption in Mice. (2016)
  • Author(s): Xu C, Ochi H, Fukuda T, Sato S, Sunamura S, Takarada T, Hinoi E, Okawa A, Takeda S.
  • Journal Title: J Bone Miner Res. Volume: -
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Genetic determination of the cellular basis of the ghrelin-dependent bone remodeling. (2015)
  • Author(s): Chengshan Ma, Toru Fukuda, Hiroki Ochi, Satoko Sunamura, Cheng Xu, Ren Xu, Atsushi Okawa, Shu Takeda
  • Journal Title: Mol Metab Volume: 4 Issue: 3 Pages: 175-185
  • DOI: 10.1016/j.molmet.2015.01.002
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] MicroRNA-145 regulates osteoblastic differentiation by targeting the transcription factor Cbfb. (2015)
  • Author(s): Fukuda T, Ochi H, Sunamura S, Haiden A, Bando W, Inose H, Okawa A, Asou Y, Takeda S.
  • Journal Title: FEBS Lett. Volume: 589 Issue: 21 Pages: 3302-8
  • DOI: 10.1016/j.febslet.2015.09.024
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] A Comparison of the Process of Remodeling of Hydroxyapatite/Poly-D/L-Lactide and Beta-Tricalcium Phosphate in a Loading Site. (2015)
  • Author(s): Akagi H, Ochi H, Soeta S, Kanno N, Yoshihara M, Okazaki K, Yogo T, Harada Y, Amasaki H, Hara Y.
  • Journal Title: Biomed Res Int. Volume: 2015 Pages: 730105-730105
  • DOI: 10.1155/2015/730105
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Bone morphogenetic protein 4 and bone morphogenetic protein receptor expression in the pituitary gland of adult dogs in healthy condition and with ACTH-secreting pituitary adenoma. (2015)
  • Author(s): Sato A, Ochi H, Harada Y, Yogo T, Kanno N, Hara Y.
  • Journal Title: Domest Anim Endocrinol. Volume: - Pages: 126-133
  • DOI: 10.1016/j.domaniend.2015.09.004
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] The Two Sides of Vitamin E Supplementation. (2014)
  • Author(s): Ochi H, Takeda S.
  • Journal Title: Gerontology Volume: - Issue: 4 Pages: 319-26
  • DOI: 10.1159/000366419
  • Peer Reviewed