Elucidation of renin-angiotensin system roles in osteocyte and development of novel osteogenic medication.

• Project/Area Number: 26713048
• Research Category: Grant-in-Aid for Young Scientists (A)
• Allocation Type: Partial 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, 医歯(薬)学総合研究科, 助教 (30582283)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥23,660,000 (Direct Cost: ¥18,200,000、Indirect Cost: ¥5,460,000); Fiscal Year 2016: ¥7,800,000 (Direct Cost: ¥6,000,000、Indirect Cost: ¥1,800,000); Fiscal Year 2015: ¥7,800,000 (Direct Cost: ¥6,000,000、Indirect Cost: ¥1,800,000); Fiscal Year 2014: ¥8,060,000 (Direct Cost: ¥6,200,000、Indirect Cost: ¥1,860,000)
• Keywords: 骨細胞 / レニンアンギオテンシン系 / 骨代謝 / レニン・アンジオテンシン / RAS

Outline of Final Research Achievements

In this study, we evaluated the significance of the renin angiotensin system in osteocytes by using osteocyte-specific RAS related gene deficient mice. These conditional knockout mice showed excessive bone mass in cortical bone. Osteoblast activities in cortical bone were significantly increased by bone morphological analysis. These findings suggest that RAS related gene in osteocyte regulates osteoblast function negatively and then maintains bone remodeling.

Research Products

• [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] 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] 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] 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] 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
• [Journal Article] Antimicrobial susceptibility of enterococcal species isolated from antibiotic-treated dogs and cats. (2014)
  • Author(s): Kataoka Y, Umino Y, Ochi H, Harada K, Sawada T.
  • Journal Title: J Vet Med Sci Volume: 76 Pages: 1399-1402
  • NAID: 130004704115
  • Peer Reviewed / Open Access
• [Journal Article] Tibial displacement with stifle joint flexion and cranial cruciate ligament transection in the dog. An ex vivo study using a robotic simulator. (2014)
  • Author(s): Kanno N, Hara Y, Fukano S, Fujie H, Ochi H, Fujita Y, Yasuji H, Nezu Y, Yogo T, Tagawa M
  • Journal Title: Vet Comp Orthop Traumatol Volume: 27 Issue: 04 Pages: 277-284
  • DOI: 10.3415/vcot-13-06-0080
  • Peer Reviewed
• [Presentation] グレリンは骨芽細胞に作用し骨形成を促進する (2014)
  • Author(s): 越智広樹、馬 成山、福田 亨、砂村聡子、大川 淳、竹田 秀
  • Organizer: 第32回日本骨代謝学会学術集会
  • Place of Presentation: 大阪国際会議場（大阪府、大阪市）
  • Year and Date: 2014-07-21 – 2014-07-23
• [Presentation] グレリンは骨芽細胞に作用し骨形成を促進する (2014)
  • Author(s): 越智広樹、馬 成山、福田 亨、砂村聡子、大川 淳、竹田 秀
  • Organizer: 第14回東京骨関節フォーラム
  • Place of Presentation: 昭和大学（東京都、品川区）
  • Year and Date: 2014-07-19