Research of therapeutics for the bone resorption-related disease targeting lipid-related GPCR based on the molecular phylogenetic analysis

• Project/Area Number: 16H05545
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Surgical dentistry
• Research Institution: Kyushu Dental College
• Principal Investigator: Hikiji Hisako 九州歯科大学, 歯学部, 教授 (50292876)
• Co-Investigator(Kenkyū-buntansha): 冨永 和宏 九州歯科大学, 歯学部, 教授 (40188793) ; 西原 達次 九州歯科大学, 歯学部, 特任教授 (80192251)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥17,160,000 (Direct Cost: ¥13,200,000、Indirect Cost: ¥3,960,000); Fiscal Year 2018: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2017: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2016: ¥7,540,000 (Direct Cost: ¥5,800,000、Indirect Cost: ¥1,740,000)
• Keywords: 口腔外科一般 / 生理活性脂質 / 口腔外科学一般 / 歯学

Outline of Final Research Achievements

The role of the lysophospholipid acyl transferases, the enzymes which are related to the biosynthesis of bioactive lipids and those receptors is elucidated in this study. For examples, the function of these enzymes in the differentiation of chondrocytes is clarified.
Furthermore, knowledge concerning macrophages, bone-related cells and nerve cells are acquired in the field of oral surgery.

Academic Significance and Societal Importance of the Research Achievements

骨吸収性疾患と生理活性脂質およびGPCRを主とするその受容体の関連性は、重要性が予想されるにも関わらず、ほとんど研究されていなかった。われわれは、生理活性脂質、そのGPCR、関連酵素群の解明を行い、GPCR 関連生理活性脂質の機能を明らかにした。すなわち、生理活性脂質の代謝活性、細胞内シグナル伝達機構の解析を行った。
これらの物質の治療応用基盤を築き、将来の創薬の道を開くことができた。

Research Products

• [Journal Article] Macrophage-mediated repair of intraepithelial damage in rat oral mucosa (2019)
  • Author(s): Myose Yasuna、Hikiji Hisako、Tsujisawa Toshiyuki、Sonoki Kazuo、Yada Naomi、Inoue Hiromasa
  • Journal Title: Archives of Oral Biology Volume: 97 Pages: 185-190
  • DOI: 10.1016/j.archoralbio.2018.10.034
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Methylation and expression status of SOCS1 and SOCS3 in oral lichen planus. (2018)
  • Author(s): Kurara Yoshimura, Naomi Yada, Kou Matsuo, Hisako Hikiji, Daigo Yoshiga1, Manabu Habu1, Masaaki Sasaguri1, Kazuhiro Tominaga.
  • Journal Title: Open Journal of Stomatology Volume: 8 Pages: 168-181
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Ky-2, a hybrid compound histone deacetylase inhibitor, regulated inflammatory response in LPS-driven human macrophages (2018)
  • Author(s): Kaneko Junya、Okinaga Toshinori、Ariyoshi Wataru、Hikiji Hisako、Fujii Seiko、Iwanaga Kenjiro、Tominaga Kazuhiro、Nishihara Tatsuji
  • Journal Title: Cell Biology International Volume: 42 Issue: 12 Pages: 1622-1631
  • DOI: 10.1002/cbin.11058
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Transducin-like Enhancer of Split 3 regulates proliferation of melanoma cells via histone deacetylase activity (2018)
  • Author(s): Ogawa M, Yaginuma T, Nakatomi C, Nakajima T, Tada-Shigeyama Y, Addison WN, Urata M, Matsubara M, Watanabe K, Matsuo K, Sato T, Honda H, Hikiji H, Watanabe S, Kokabu S
  • Journal Title: Oncotarget Volume: 10(3) Issue: 3 Pages: 404-414
  • DOI: 10.18632/oncotarget.26552
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Zoledronic acid exacerbates inflammation through M1 macrophage polarization. (2018)
  • Author(s): Kaneko J, Okinaga T, Hikiji H, Ariyoshi W, Yoshiga D, Habu M, Tominaga K, Nishihara T.
  • Journal Title: Inflammation and Regeneration Volume: -
  • Peer Reviewed
• [Journal Article] 1.Lysophosphatidylcholine acyltransferase 4 is involved in chondrogenic differentiation of ATDC5 cells. (2017)
  • Author(s): Tabe S, Hikiji H, Ariyoshi W, Hashidate-Yoshida T, Shindou H, Shimizu T, Okinaga T, Seta Y, Tominaga K, Nishihara T.
  • Journal Title: Sci Rep. Volume: 7 Issue: 1 Pages: 1-11
  • DOI: 10.1038/s41598-017-16902-4
  • Peer Reviewed / Open Access
• [Journal Article] 終末期がん患者に対する口腔ケアがQOLにおよぼす効果 (2017)
  • Author(s): 高橋由希子,伊藤恵美,亀岡祐一,引地尚子
  • Journal Title: 九州歯会誌 Volume: 印刷中
  • Peer Reviewed
• [Journal Article] Lysophosphatidylethanolamina acyltransfcrase/membrane-bound O-acyltransferase 1 regulates morphology and function of P19C6 cell-derived neurons. (2016)
  • Author(s): Tabe S， Hikiji H， Ariyoshi W， Hashidate-Yoshida T， Shindou H，Okinaga T， Shimizu T， Tominaga K，Nishihara T.
  • Journal Title: FASEB. J Volume: 30 Issue: 7 Pages: 2591-2601
  • DOI: 10.1096/fj.201500097r
  • Peer Reviewed / Acknowledgement Compliant
• [Presentation] Effect of polyunsaturated fatty acids on macrophage polarization, (2018)
  • Author(s): Aki Kawano, Toshinori Okinaga, Wataru Ariyoshi, Hisako Hikiji and Tatsuji Nishihara.
  • Organizer: Asia Pacific Conference 2018
  • Int'l Joint Research
• [Presentation] 内在性ヒアルロン酸が及ぼす破骨細胞支持能への影響. (2018)
  • Author(s): 中尾優子，引地尚子，吉岡泉．
  • Organizer: 第31回 日本顎関節症学会総会・学術大会
• [Presentation] マクロファージ系細胞の分化に対する多価不飽和脂肪酸の影響． (2018)
  • Author(s): 川野亜希，沖永敏則，有吉渉，引地尚子，西原達次.
  • Organizer: 第39回日本炎症・再生医学会
• [Presentation] 軟骨細胞分化過程におけるリゾリン脂質アシル転移酵素の働き． (2018)
  • Author(s): 田部士郎，引地尚子，土生学，笹栗正明，冨永和宏.
  • Organizer: 第63回日本口腔外科学会総会および学術大会
• [Presentation] Ｍ１マクロファージ分化誘導モデルにおけるビスフォスフォネートの影響． (2017)
  • Author(s): 金子純也，引地尚子，吉賀大午, 土生学, 笹栗正明，田中純平，坂口修，鶴島弘基，吉岡泉，冨永和宏．
  • Organizer: 第71回 NPO法人日本口腔科学会学術集会
• [Presentation] Zoledronic acid regulates M1 macrophage polarization induced by lipopolysaccharides. (2017)
  • Author(s): Junya Kaneko, Hisako Hikiji, Toshinori Okinaga, Wataru Ariyoshi， Daigo Yoshiga，Manabu Habu，Masaaki Sasaguri，Junpei Tanaka, Osamu Sakaguchi, Hiroki Tsurushima, Izumi Yoshioka, Tatsuji Nishihara and Kazuhiro Tominaga.
  • Organizer: Asia-Pacific Conference in Fukuoka.
• [Presentation] 薬剤関連性顎骨瘢死におけるM1マクロファージの影響． (2017)
  • Author(s): 金子純也，引地尚子，沖永敏則，有吉 渉，吉賀大午，冨永和宏，西原達次．
  • Organizer: 第76回九州歯科学会総会学術大会
• [Presentation] ヒストン脱アセチル化酵素阻害剤はマクロファージ分化ＴＨＰ-1細胞からの炎症性サイトカインの産生を抑制する． (2017)
  • Author(s): 金子純也，沖永敏則，引地尚子，有吉渉，藤井誠子，高橋理，西原達次．
  • Organizer: 第59回歯科基礎医学会学術大会
• [Presentation] 口腔ケアを想定した口腔粘膜上皮軽微損傷の特異的治癒過程の解析． (2017)
  • Author(s): 明瀬靖奈，引地尚子．
  • Organizer: 第17回日本再生医療学会総会再生医療学会
• [Presentation] マクロファージ分化におけるω-3系脂肪酸の役割． (2016)
  • Author(s): 川野亜希，沖水敏則，引地尚子，有吉渉，西原達次.
  • Organizer: 第58回 歯科・基礎医学会学術大会
  • Place of Presentation: 札幌コンベンションセンター，札幌
  • Year and Date: 2016-08-24
• [Presentation] LPS誘導M1マクロファージ分化におけるビスフォスフォネートの影響 (2016)
  • Author(s): 金子純也，引地尚子，沖水敏則，有吉渉，西原達次
  • Organizer: 第58回 歯科・基礎医学会学術大会
  • Place of Presentation: 札幌コンベンションセンター，札幌
  • Year and Date: 2016-08-24
• [Presentation] Lysophosphatidylethanolamine Acyltransferase 1 Regulates Morphology and Function of P19C6 Cell-derived Neurons. (2016)
  • Author(s): Shirou Tabe, Hisako Hikiji, Toshinori Okinaga, and Tatsuji Nishihara.
  • Organizer: IADR/APR General Session & Exhibition
  • Place of Presentation: Seoul, Korea
  • Year and Date: 2016-06-22
  • Int'l Joint Research