Evaluation of functions of novel adapter molecules on bone metabolism and orthodontic tooth movement

• Project/Area Number: 16K11776
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Orthodontics/Pediatric dentistry
• Research Institution: Tohoku University
• Principal Investigator: Kitaura Hideki 東北大学, 歯学研究科, 准教授 (60295087)
• Co-Investigator(Kenkyū-buntansha): 福永 智広 東北大学, 大学病院, 講師 (70362994) ; 木村 桂介 東北大学, 歯学研究科, 大学院非常勤講師 (70712909) ; 石田 匡彦 東北大学, 大学病院, 助教 (80770891)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2016: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: 破骨細胞 / 矯正歯科 / 歯学 / 細胞・組織 / 免疫学

Outline of Final Research Achievements

It has been reported that ITAM is essential for osteoclast differentiation, since the double-defective mouse of adapter molecules FcRγ and DAP12 with ITAM shows a differentiation failure of osteoclasts. A STAM including ITAM motif has been identified as a functional molecule involved in cell proliferation signal transduction. Osteoclastogenesis was carried out by overexpressing STAM1 molecules in osteoclast precursor cells prepared from wild-type mice using a retrovirus. Overexpression of STAM1 promoted osteoclastogenesis. On the other hand, osteoclast formation was suppressed when knockdown of STAM1 was performed using shRNA to osteoclast precursor cells. The results suggested that STAM play an important role in osteoclast formation.

Academic Significance and Societal Importance of the Research Achievements

破骨細胞形成には、カルシウムシグナリングが必須と言われ、ITAMを有するDAP12またはFcRγを介してのシグナル伝達が重要であることが報告されているが、DAP12およびFcRγ二重遺伝子欠損マウスにおいても完全に破骨細胞形成が抑制されなかったことから新規のカルシウムシグナル伝達の経路があることが示唆されている。本研究では、STAMが破骨細胞形成に重要な働きをしていることがわかった。本研究は、破骨細胞形成のメカニズムの解明には必須の研究であり、骨吸収を伴う疾患の治療や予防および矯正学的歯の移動の制御につながると考えている。

Research Products

• [Journal Article] Docosahexaenoic Acid Inhibits Inflammation-Induced Osteoclast Formation and Bone Resorption in vivoThrough GPR120 by Inhibiting TNF-α Production in Macrophages and Directly Inhibiting Osteoclast Formation (2019)
  • Author(s): Akiko Kishikawa, Hideki Kitaura, Keisuke Kimura, Saika Ogawa, Jiawei Qi, Wei-Ren Shen, Fumitoshi Ohori, Takahiro Noguchi, Aseel Marahleh, Yasuhiko Nara, Atsuhiko Ichimura, Itaru Mizoguchi
  • Journal Title: frontier in endocrinology Volume: Volume 10 Pages: 157-157
  • DOI: 10.3389/fendo.2019.00157
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Effect of Anti-c-fms Antibody on Osteoclast Formation and Proliferation of Osteoclast Precursor In Vitro (2019)
  • Author(s): Marahleh A, Kitaura H, Ishida M, Shima K, Kishikawa A, Ogawa S, Shen WR, Qi J, Ohori F, Noguchi T, Nara Y, Mizoguchi I
  • Journal Title: J Vis Exp Volume: 18 Issue: 145 Pages: 145-145
  • DOI: 10.3791/59089
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] DPP-4 inhibitor impedes lipopolysaccharide-induced osteoclast formation and bone resorption in vivo. (2019)
  • Author(s): Ishida M, Shen WR, Kimura K, Kishikawa A, Shima K, Ogawa S, Qi J, Ohori F, Noguchi T, Marahleh A, Kitaura H.
  • Journal Title: Biomed. Pharmacother. Volume: 109 Pages: 242-253
  • DOI: 10.1016/j.biopha.2018.10.052
  • Peer Reviewed / Open Access
• [Journal Article] C-X-C motif chemokine 12 enhances lipopolysaccharide-induced osteoclastogenesis and bone resorption in vivo. (2018)
  • Author(s): Shima K, Kimura K, Ishida M, Kishikawa A, Ogawa S, Qi J, Shen WR, Ohori F, Noguchi T, Marahleh A, Kitaura H.
  • Journal Title: Calcif. Tissue Int. Volume: 103 Issue: 4 Pages: 431-442
  • DOI: 10.1007/s00223-018-0435-z
  • Peer Reviewed / Open Access
• [Journal Article] The glucagon-like peptide-1 receptor agonist exendin-4 inhibits lipopolysaccharide-induced osteoclast formation and bone resorption via inhibition of TNF-α expression in macrophages. (2018)
  • Author(s): Wei-Ren Shen, Keisuke Kimura, Masahiko Ishida, Haruki Sugisawa, Akiko Kishikawa, Kazuhiro Shima, Saika Ogawa, Jiawei Qi, Hideki Kitaura
  • Journal Title: Journal of Immunology Research Volume: 2018 Pages: 5783639-5783639
  • DOI: 10.1155/2018/5783639
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] 過去9年間の東北大学病院矯正歯科における歯科矯正用アンカースクリューの動向調査 (2018)
  • Author(s): 真山敦、清流正弘、出口徹、金原正敬、岩崎将也、解良洋平、宮下俊郎、関大輔、竹下信郎、福永智広、北浦英樹、山本照子
  • Journal Title: 東北矯正歯科学会雑誌 Volume: 26 Pages: 3-8
  • Peer Reviewed
• [Journal Article] 東北大学病院矯正歯科における包括的歯科治療へのアプローチ (2018)
  • Author(s): 関大輔、北浦英樹、山本照子
  • Journal Title: 東北矯正歯科学会雑誌 Volume: 26 Pages: 121-125
• [Journal Article] Corrosion resistance and mechanical properties of titanium nitride plating on orthodontic wires (2018)
  • Author(s): Sugisawa, H., Kitaura, H., Ueda, K., Kimura, K., Ishida, M., Ochi, Y., Kishikawa, A., Ogawa, S., Takano-Yamamoto T
  • Journal Title: Dental Materials Journal Volume: 37 Issue: 2 Pages: 286-292
  • DOI: 10.4012/dmj.2016-348
  • NAID: 130006588780
  • ISSN: 0287-4547, 1881-1361
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Role of muramyl dipeptide for lipopolysaccharide-mediated biological activity and osteoclast activity. (2018)
  • Author(s): Kitaura, H., Ishida, M., Kimura, K., Sugisawa, H., Kishikawa A, Shima, K., Ogawa S., Qi J, Kitaura H., Shen WR
  • Journal Title: Anal. Cell. Pathol. Volume: Volume 2018 Pages: 8047610-8047610
  • DOI: 10.1155/2018/8047610
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] 歯科矯正用Ni-Tiワイヤーに対する表面コーティングによる耐食性の解析 (2017)
  • Author(s): 木村桂介，杉澤晴紀，井田裕人，石田匡彦，島和弘，岸川明子，小川紗衣香，北浦英樹
  • Journal Title: 東北矯正歯科学会雑誌 Volume: 25 Pages: 9-15
  • Peer Reviewed
• [Journal Article] 歯科矯正用アンカースクリューを用いた矯正歯科治療および臨床研究 (2017)
  • Author(s): 清流正弘、福永智広、北浦英樹、山本照子
  • Journal Title: 東北矯正歯科学会雑誌 Volume: 25 Pages: 49-53
  • Peer Reviewed
• [Journal Article] IL-37 inhibits lipopolysaccharide-induced osteoclast formation and bone resorption in vivo. (2016)
  • Author(s): Saeed J, Kitaura H, Kimura K, Ishida M, Sugisawa H, Ochi Y, Kishikawa A, Takano-Yamamoto T
  • Journal Title: Immunol Lett. Volume: 175 Pages: 8-15
  • DOI: 10.1016/j.imlet.2016.04.004
  • Peer Reviewed / Open Access
• [Presentation] Biological mechanism of orthodontic tooth movement. (2019)
  • Author(s): Kitaura, H.
  • Organizer: International Symposium for Interface Oral Health Science 2019
  • Int'l Joint Research / Invited
• [Presentation] G-Protein Coupled Receptor 120(GPR120)刺激における破骨細胞形成および骨吸収に対する影響について (2019)
  • Author(s): 岸川明子、北浦英樹、木村桂介、小川紗衣香、斉嘉韋、沈威任、大堀文俊、野口隆弘、Marahleh Aseel Mahmoud、奈良靖彦、市村敦彦、溝口到
  • Organizer: 第40回東北骨代謝・骨粗鬆症研究会
• [Presentation] Investigation of the effect of TNF-α on RANKL expression in osteocytes. (2018)
  • Author(s): Marahleh A, Kimura K, Kishikawa A, Shima K, Ogawa S, Qi J, Shen WR, Ohori F, Noguchi T, Kitaura H.
  • Organizer: The 77th Annual Meeting of the Japanese Orthodontic Society.
  • Int'l Joint Research
• [Presentation] Glucagon-like Peptide-1 Receptor Agonist Ameliorates Lipopolysaccharide-induced Osteoclast Formation Through inhibiting of TNF-α production in macrophages. (2018)
  • Author(s): Shen WR, Ishida M, Kimura K, Kishikawa A, Shima K, Ogawa S, Qi J, Ohori F, Noguchi T, Marahleh A, Kitaura H.
  • Organizer: The 77th Annual Meeting of the Japanese Orthodontic Society.
  • Int'l Joint Research
• [Presentation] Establishment of orthodontic retention mouse model and inhibition of orthodontic relapse by anti-c-Fms antibody. (2018)
  • Author(s): Qi J, Kimura K, Kishikawa A, Ogawa S, Shen WR, Ohori F, Noguchi T, Marahleh A, Kitaura H.
  • Organizer: The 77th Annual Meeting of the Japanese Orthodontic Society.
  • Int'l Joint Research
• [Presentation] The effect of an anti-c-Fms antibody on orthodontic relapse in mouse. (2018)
  • Author(s): Qi J, Kimura K, Ishida M, Kishikawa A, Shima K, Ogawa S, Shen WR, Ohori F, Noguchi T, Marahleh A, Kitaura H.
  • Organizer: American Society for Bone and Mineral Research 2018 Annual Meeting.
  • Int'l Joint Research
• [Presentation] DPP-4 Inhibitor inhibits LPS-induced osteoclast formation and bone resorption in vivo through downergulating TNF-α expression of macrophages. (2018)
  • Author(s): Shen WR, Ishida M, Kimura K, Kishikawa A, Shima K, Ogawa S, Qi J, Ohori F, Noguchi T, Marahleh A, Kitaura H.
  • Organizer: American Society for Bone and Mineral Research 2018 Annual Meeting.
  • Int'l Joint Research
• [Presentation] G Protein-Coupled Receptor 120 signaling inhibited osteoclast formation and bone resorption. (2018)
  • Author(s): Kishikawa A, Kimura K, Ishida M, Shima K, Ogawa S, Qi J, Shen WR, Ohori F, Noguchi T, Marahleh A, Kitaura H.
  • Organizer: American Society for Bone and Mineral Research 2018 Annual Meeting.
  • Int'l Joint Research
• [Presentation] Effect of C-X-C motif chemokine 12 in lipopolysaccharide-induced osteoclast formation and bone resorption. (2018)
  • Author(s): Kitaura H., Shima K, Kimura K, Ishida M, Kishikawa A, Ogawa S, Qi J, Shen WR, Ohori F, Noguchi T, Marahleh A,
  • Organizer: American Society for Bone and Mineral Research 2018 Annual Meeting.
  • Int'l Joint Research
• [Presentation] Anti-c-Fms antibody inhibits orthodontic relapse in a mouse model. (2018)
  • Author(s): Qi J, Kitaura H., Ogawa S, Shen WR, Ohori F, Noguchi T, Marahleh A, Mizoguchi I.
  • Organizer: The 13th International Workshop on Biomaterials in Interface Science. Innovative Research for Biosis-Abiosis Intelligent Interface Summer Seminar 2018
  • Int'l Joint Research
• [Presentation] Comparisons with and without retention in orthodontic relapse mouse models. (2018)
  • Author(s): Qi J, Kimura K, Ishida M, Kishikawa A, Shima K, Ogawa S, Shen WR, Ohori F, Noguchi T, Marahleh A, Kitaura H.
  • Organizer: International Symposium for Multimodal Research and Education in IOHS-Liaison 2018
  • Int'l Joint Research
• [Presentation] Inhibition of lipopolysaccharide-induced osteoclast formation and bone resorption in vivo by glucagon-like peptide-1 receptor agonist. (2018)
  • Author(s): Shen WR, Kimura K, Ishida M, Kishikawa A, Shima K, Ogawa S, Qi J, Ohori F, Noguchi T, Marahleh A, Kitaura H.
  • Organizer: International Symposium for Multimodal Research and Education in IOHS-Liaison 2018
  • Int'l Joint Research
• [Presentation] 最近の矯正歯科における金属アレルギーについて (2018)
  • Author(s): 北浦英樹
  • Organizer: 第77回日本矯正歯科学会大会
• [Presentation] TNF-αによる骨細胞と矯正学的歯の移動におけるsclerostin発現解析 (2018)
  • Author(s): 大堀文俊、木村桂介、岸川明子、小川紗衣香、斉嘉韋、沈威任、野口隆弘、Marahleh Aseel、北浦英樹
  • Organizer: 第77回日本矯正歯科学会大会
• [Presentation] TNF-αのRANK発現への影響および矯正学的歯の移動時のRANK発現について (2018)
  • Author(s): 野口隆弘、木村桂介、岸川明子、小川紗衣香、斉嘉韋、沈威任、大堀文俊、Marahleh Aseel Mahmoud、北浦英樹
  • Organizer: 第77回日本矯正歯科学会大会
• [Presentation] CXCL12の破骨細胞形成、骨吸収および破骨細胞関連サイトカインの発現への影響についての検討 (2018)
  • Author(s): 島和弘、木村桂介、石田匡彦、岸川明子、小川紗衣香、斉嘉韋、沈威任、大堀文俊、野口隆弘、Marahleh Aseel Mahmoud、北浦英樹
  • Organizer: 第77回日本矯正歯科学会大会
• [Presentation] 破骨細胞形成、骨吸収および破骨細胞関連サイトカインの発現への糖尿病治療薬DPP-4阻害剤の影響 (2018)
  • Author(s): 石田匡彦、沈威任、木村桂介、石田匡彦、島和弘、岸川明子、小川紗衣香、斉嘉韋、大堀文俊、野口隆弘、Marahleh Aseel Mahmoud、北浦英樹
  • Organizer: 第77回日本矯正歯科学会大会
• [Presentation] コーティング歯科矯正用ワイヤーの耐食性の解析 (2018)
  • Author(s): 木村桂介、井田裕人、石田匡彦、島和弘、岸川明子、小川紗衣香、北浦英樹
  • Organizer: 第77回日本矯正歯科学会大会
• [Presentation] 東北大学病院矯正歯科における歯科矯正用アンカースクリューに関する臨床調査 (2018)
  • Author(s): 真山敦、清流正弘、出口徹、金原正敬、岩崎将也、解良洋平、宮下俊郎、関大輔、竹下信郎、福永智広、北浦英樹、山本照子
  • Organizer: 第77回日本矯正歯科学会大会
• [Presentation] 外科的矯正歯科治療により形態および顎機能の改善が認められた前歯部開咬を伴う骨格性III級の下顎偏位症例 (2018)
  • Author(s): 関大輔、北浦英樹、山本照子
  • Organizer: 第77回日本矯正歯科学会大会
• [Presentation] 歯科矯正用Ni-Tiワイヤーの耐食性の解析 (2018)
  • Author(s): 木村桂介，井田裕人，石田匡彦，島和弘，岸川明子，小川紗衣香，北浦英樹
  • Organizer: 第34回東北矯正歯科学会大会
• [Presentation] 術前に片側性咀嚼筋・腱膜過形成症を呈した骨格性下顎後退症の一例 (2018)
  • Author(s): 奥山喬助、山内健介、片岡良造、斎藤志都、鈴木飛佳理、山口佳宏、佐藤工、阿部陽子、野上晋之介、坂東加南、北浦英樹、高橋哲
  • Organizer: 第28回日本顎変形症学会
• [Presentation] Effect of IL-18 on mechanical loading-induced osteoclastogenesis and bone resorption. (2017)
  • Author(s): Ochi Y, Kitaura H, Kimura K, Ishida M, Sugisawa H, Saeed J, Kishikawa A, Qi J, Takano-Yamamoto T.
  • Organizer: The 2017 Japan-NIH joint Symposium
  • Place of Presentation: 星陵オーディトリアム（宮城県）
  • Year and Date: 2017-02-15
  • Int'l Joint Research
• [Presentation] Exendin-4, a GLP-1 receptor agonist, suppresses inflammation-induced osteoclast formation and bone resorption. (2017)
  • Author(s): Shen WR, Kimura K, Ishida M, Sugisawa H, Ochi Y, Kishikawa A, Shima K, Ogawa S., Qi J, Kitaura H.
  • Organizer: The 12th International Workshop on Biomaterials in Interface Science.
  • Int'l Joint Research
• [Presentation] The effects of diabetic medicine exendin-4 for osteoclast formation and bone resorption. (2017)
  • Author(s): Shen WR, Kimura K, Ishida M, Sugisawa H, Ochi Y, Kishikawa A, Shima K, Ogawa S., Qi J, Kitaura H.
  • Organizer: The 76th Annual Meeting of the Japanese Orthodontic Society.
• [Presentation] 歯科矯正用アンカースクリューを用いて水平的な咬合平面の傾斜を改善した正中離開症例 (2017)
  • Author(s): 吉澤 光弘、北浦 英樹、福永 智広、山本 照子
  • Organizer: 第33回東北矯正歯科学会大会
• [Presentation] RUNK2+/-マウスの矯正的はの移動の牽引側における骨芽細胞の増殖および分化気候にRunx2/mTORC2シグナルが関与する (2017)
  • Author(s): 青沼 智、福永智広、北浦英樹、竹下信郎、山城隆、山本照子
  • Organizer: 第35回日本骨代謝学会学術集会
• [Presentation] 脂肪酸受容体GPR120の破骨細胞形成および骨吸収との関連性の検討 (2017)
  • Author(s): 木村桂介、石田匡彦、島和弘、杉澤晴紀、越智由美子、岸川明子、小川紗衣香、斉嘉韋、沈威任、北浦英樹
  • Organizer: 第76回日本矯正歯科学会大会
• [Presentation] 破骨細胞形成および骨吸収に対する脂肪細胞に発現するケモカインCXCL12の作用の検討 (2017)
  • Author(s): 島和弘、木村桂介、石田匡彦、杉澤晴紀、越智由美子、岸川明子、小川紗衣香、斉嘉韋、沈威任、北浦英樹
  • Organizer: 第76回日本矯正歯科学会大会
• [Presentation] 糖尿病治療薬DPP-4阻害薬による破骨細胞形成および骨吸収への影響について (2017)
  • Author(s): 石田匡彦、木村桂介、島和弘、沈威任、北浦英樹
  • Organizer: 第76回日本矯正歯科学会大会
• [Presentation] 小脳髄芽腫の開頭手術後の左側顔面麻痺および側方性開咬を呈する症例 (2017)
  • Author(s): 佐々木聡、北浦英樹、岩崎将也、原真美子、山本照子
  • Organizer: 第76回日本矯正歯科学会大会
• [Presentation] TiNコーティングを施した歯科矯正用ワイヤーの摩擦力の検討 (2017)
  • Author(s): 杉澤晴紀、北浦英樹、上田恭介、木村桂介、石田匡彦、越智由美子、岸川明子、小川紗衣香、山本照子
  • Organizer: 第76回日本矯正歯科学会大会
• [Presentation] 矯正学的歯の移動における破歯細胞形成および歯根吸収へのTNF-αの関与について (2016)
  • Author(s): 北浦英樹、木村桂介、石田匡彦、杉澤晴紀、越智由美子、岸川明子、Qi Jiawei、山本照子
  • Organizer: 第75回日本矯正歯科学会
  • Place of Presentation: アスティとくしま（徳島県）
  • Year and Date: 2016-11-07
• [Presentation] 破骨細胞形成および骨吸収に対するIL-37の作用の検討 (2016)
  • Author(s): 木村桂介、北浦英樹、石田匡彦、杉澤晴紀、越智由美子、岸川明子、Qi Jiawei、ジャファリ、山本照子
  • Organizer: 第75回日本矯正歯科学会
  • Place of Presentation: アスティとくしま（徳島県）
  • Year and Date: 2016-11-07
• [Presentation] Oral health-related quality of life and perceptions of jaw dysfunction and maxillofacial asymmetry in orthodontic patients. (2016)
  • Author(s): Kitaura H, Kuroki T, Ishida M, Kimura K, Takano-Yamamoto T.
  • Organizer: The 23rd General Meeting of the Japanese Association for Dental Science.
  • Place of Presentation: 福岡国際会議場（福岡県）
  • Year and Date: 2016-10-21
  • Int'l Joint Research
• [Presentation] Analysis of friction of titanium nitride plating on orthodontic wires. (2016)
  • Author(s): Sugisawa H., Kitaura H., Ueda K., Kimura K., Ishida M., Ochi Y, Kishikawa A., Ogawa S., Takano-Yamamoto T.
  • Organizer: 11th Anniversary International Workshop on Biomaterials in Interface Science. Innovative Research for Biosis-Abiosis Intelligent Interface Summer Seminar 2016
  • Place of Presentation: バーデン家壮鳳（宮城県）
  • Year and Date: 2016-08-30
  • Int'l Joint Research