Development of new regeneration therapy using strong osteoplasty protein BMP-9 and cells derived from adipose tissue

• Project/Area Number: 15H05036
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Dental engineering/Regenerative dentistry
• Research Institution: Kagoshima University
• Principal Investigator: NOGUCHI Kazuyuki 鹿児島大学, 医歯学域歯学系, 教授 (90218298)
• Co-Investigator(Kenkyū-buntansha): 白方 良典 鹿児島大学, 医歯学域歯学系, 准教授 (60359982) ; 中村 利明 鹿児島大学, 医歯学域附属病院, 講師 (60381183) ; 瀬名 浩太郎 鹿児島大学, 医歯学域歯学系, 助教 (60701117) ; 迫田 賢二 鹿児島大学, 医歯学域歯学系, 助教 (70419654)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥17,290,000 (Direct Cost: ¥13,300,000、Indirect Cost: ¥3,990,000); Fiscal Year 2017: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000); Fiscal Year 2016: ¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000); Fiscal Year 2015: ¥7,670,000 (Direct Cost: ¥5,900,000、Indirect Cost: ¥1,770,000)
• Keywords: DFAT / BMP-9 / 歯周病 / 骨組織再生 / 歯周組織再生 / 細胞移植 / 培養上清 / 再生療法 / FK-506 / ADSC

Outline of Final Research Achievements

The purpose of this study was development of new regenerative therapy for lost bone tissues due to periodontal and oral disease by using FK506 together with BMP-9 for signal molecules and stem cells (ADSC) and dedifferentiated fat cells(DFAT) which derived from adipose tissue as a source of cell transplant. In vitro study demonstrated that BMP-9 and FK506 costimulation induces promotion of osteoblasts-like differentiation in both rat ADSC and rat DFAT. Furthermore , we demonstrated that rDFAT cells culture supernatant of BMP-9 and FK506 costimulation have bone regenerative potential in rat calvarial defects model.

Research Products

• [Journal Article] Development of a new model for training of initial periodontal therapy (2018)
  • Author(s): 町頭 三保、梅田 誠、野口 和行、中村 利明、白方 良典、中村 梢、迫田 賢二、瀬名 浩太郎、篠原 敬哉、橋口 千琴、田口 洋一郎
  • Journal Title: Nihon Shishubyo Gakkai Kaishi (Journal of the Japanese Society of Periodontology) Volume: 60 Issue: 1 Pages: 44-51
  • DOI: 10.2329/perio.60.44
  • NAID: 130006594272
  • ISSN: 0385-0110, 1880-408X
  • Peer Reviewed / Open Access
• [Journal Article] Periodontal wound healing following reciprocal autologous root transplantation in class III furcation defects (2017)
  • Author(s): Takeuchi Naoshi、Shirakata Yoshinori、Shinohara Yukiya、Sena Kotaro、Noguchi Kazuyuki
  • Journal Title: Journal of Periodontal & Implant Science Volume: 47 Issue: 6 Pages: 352-352
  • DOI: 10.5051/jpis.2017.47.6.352
  • Peer Reviewed / Open Access
• [Journal Article] Site-level progression of periodontal disease during a follow-up period (2017)
  • Author(s): Nomura Yoshiaki、Yoshimura Atsutoshi、Hara Yoshitaka、Nakamura Toshiaki、Noguchi Kazuyuki、Kakuta Erika、Hanada Nobuhiro、Takashiba Shogo、Amitani Yasuharu、Yoshie Hiromasa、他
  • Journal Title: PLOS ONE Volume: 12 Issue: 12 Pages: e0188670-e0188670
  • DOI: 10.1371/journal.pone.0188670
  • Peer Reviewed / Open Access
• [Journal Article] Healing of 2-wall intrabony defects treated with a novel EMD-liquid. A preclinicalstudy in monkeys (2017)
  • Author(s): Yoshinori Shirakata, Richard J. Miron, Yukiya Shinohara, Toshiaki Nakamura, Kotaro Sena, Naoto Horai, Dieter D. Bosshardt, Kazuyuki Noguch, Anton Sculean
  • Journal Title: Journal of Clinical Periodontology Volume: 44 Issue: 12 Pages: 1264-1273
  • DOI: 10.1111/jcpe.12825
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Comparison of two porcine collagen membranes combined with recombinant human bone morphogenetic protein (rhBMP)-2 and -9 on osteoblast behavior in vitro (2017)
  • Author(s): Masako Kobayashi, Benoit Schaller, Yoshinori Shirakata, Toshiaki Nakamura, Kazuyuki Noguchi, Yufeng Zhang, Richard J. Miron.
  • Journal Title: The International Journal of Oral & Maxillofacial Implants Volume: 32 Issue: 4 Pages: e221-e230
  • DOI: 10.11607/jomi.5652
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] The Association of Periodontopathic Bacteria Levels ;in Saliva and Tongue Coating with Oral Malodor in Periodontitis Patients. (2017)
  • Author(s): Takeuchi H, Machigashira M, Takeuchi N, Nakamura T, Noguchi K
  • Journal Title: Oral Health Prev Dent Volume: 15(3) Pages: 285-291
  • Peer Reviewed / Open Access
• [Journal Article] Low-Intensity Pulsed Ultrasound (LIPUS) Promotes BMP9-Induced Osteogenesis and Suppresses Inflammatory Responses in Human Periodontal Ligament-Derived Stem Cells. (2017)
  • Author(s): Kusuyama J, Nakamura T, Ohnishi T, Eiraku N, Noguchi K, Matsuguchi T.
  • Journal Title: J Orthop Trauma. Volume: 31 Issue: 7 Pages: S4-S4
  • DOI: 10.1097/01.bot.0000520897.92470.70
  • Peer Reviewed / Open Access
• [Journal Article] A case report of desquamative gingival lesions caused by pemphigus vulgaris (2017)
  • Author(s): 堂満愛弓, 中村利明, 下田平貴子, 橋口千琴, 野口和行
  • Journal Title: Nihon Shishubyo Gakkai Kaishi (Journal of the Japanese Society of Periodontology) Volume: 59 Issue: 4 Pages: 230-240
  • DOI: 10.2329/perio.59.230
  • NAID: 130006289632
  • ISSN: 0385-0110, 1880-408X
  • Peer Reviewed / Open Access
• [Journal Article] Detection of Periodontal Pathogens in Chorionic Tissues of Pregnant Women Diagnosed with Threatened Premature Labor and Abnormal Glucose Tolerance (2017)
  • Author(s): Kozue Hasegawa-Nakamura, Toshiaki Nakamura, Masato Kamitomo, Fumi Tateishi, Chikoto Hashiguchi, Kazuya Kawamata, Masayuki Hatae, Kazuyuki Noguchi
  • Journal Title: Nihon Shishubyo Gakkai Kaishi (Journal of the Japanese Society of Periodontology) Volume: 59 Issue: 3 Pages: 133-143
  • DOI: 10.2329/perio.59.133
  • NAID: 130006105760
  • ISSN: 0385-0110, 1880-408X
  • Peer Reviewed / Open Access
• [Journal Article] Assessing the progression of chronic periodontitis using subgingival pathogen and serum antibody levels: a 24-month prospective multicenter cohort study (2017)
  • Author(s): E. Kakuta, Y. Nomura, T. Morozumi, T. Nakagawa, T. Nakamura, K. Noguchi
  • Journal Title: BMC Oral Health Volume: 17 Pages: 46-46
  • Peer Reviewed / Open Access
• [Journal Article] Comparison of the effects of recombinant human bone morphogenetic protein-2 and -9 on bone formation in rat calvarial critical-size defects. (2017)
  • Author(s): Nakamura T, Shirakata Y, Shinohara Y, Miron RJ, Hasegawa-Nakamura K, Fujioka-Kobayashi M, Noguchi K.
  • Journal Title: Clin Oral Investig. Volume: 印刷中 Issue: 9 Pages: 2671-2679
  • DOI: 10.1007/s00784-017-2069-3
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Involvement of PI3K/Akt signaling pathway in BMP9-stimulated osteogenic differentiation and SDF-1 production in human periodontal ligament fibroblasts (2017)
  • Author(s): Furue K, Sena K, Sakoda K, Nakamura T, Noguchi K.
  • Journal Title: Eur J Oral Sci. Volume: 125（2） Issue: 2 Pages: 119-126
  • DOI: 10.1111/eos.12336
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Effects of EMD liquid (Osteogain) on periodontal healing in class III furcation defects in monkeys. (2017)
  • Author(s): Shirakata Y, Miron RJ, Nakamura T, Sena K, Shinohara Y, Horai N, Bosshardt DD, Noguchi K, Sculean A.
  • Journal Title: J Clin Periodontol. Volume: 44（3） Issue: 3 Pages: 298-307
  • DOI: 10.1111/jcpe.12663
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Prevalence and risk factors for peri-implant diseases in Japanese adult dental patients (2017)
  • Author(s): Ogata Y, Nakayama Y, Tatsumi J, Kubota T, Sato S, Nishida T, Takeuchi Y, Onitsuka T, Sakagami R, Nozaki T, Murakami S, Matsubara N, Tanaka M, Yoshino T, Ota J, Nakagawa T, Ishihara Y, Ito T, Saito A, Yamaki K, Matsuzaki E, Hidaka T, Sasaki D, Yaegashi T, Yasuda T, Shibutani T, Noguchi K他
  • Journal Title: Journal of Oral Science Volume: 59 Issue: 1 Pages: 1-11
  • DOI: 10.2334/josnusd.16-0027
  • NAID: 130005519828
  • ISSN: 1343-4934, 1880-4926
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Osteogenic potential of recombinant human bone morphogenetic protein-9/absorbable collagen sponge (rhBMP-9/ACS) in rat critical size calvarial defects.，Clinical Oral Investigations (2016)
  • Author(s): Nakamura T, Shirakata Y, Shinohara Y, Miron RJ, Furue K, Noguchi K.
  • Journal Title: Clin Oral Investig. Volume: 21 （5）
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Two-Component Systems Involved in Susceptibility to Nisin A in Streptococcus pyogenes. (2016)
  • Author(s): Kawada-Matsuo M, Tatsuno I, Arii K, Zendo T, Oogai Y, Noguchi K, Hasegawa T, Sonomoto K, Komatsuzawa H.
  • Journal Title: Appl Environ Microbiol. Volume: 16；82（19） Issue: 19 Pages: 5930-5939
  • DOI: 10.1128/aem.01897-16
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Bone healing capabilities of recombinant human bone morphogenetic protein-9 (rhBMP-9) with a chitosan or collagen carrier in rat calvarial defects (2016)
  • Author(s): Yukiya Shinohara, Toshiaki Nakamura, Yoshinori Shirakata and Kazuyuki Noguchi
  • Journal Title: Dental Materials Journal Volume: 35 Issue: 3 Pages: 454-460
  • DOI: 10.4012/dmj.2015-242
  • NAID: 130005155194
  • ISSN: 0287-4547, 1881-1361
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Recombinant human bone morphogenetic protein-9 potently induces osteogenic differentiation of human periodontal ligament fibroblasts (2016)
  • Author(s): Sawako Fuchigami, Toshiaki Nakamura, Kirara Furue, Kotaro Sena, Yukiya Shinohara and Kazuyuki Noguchi
  • Journal Title: European Journal of Oral Science Volume: 124 Issue: 2 Pages: 151-157
  • DOI: 10.1111/eos.12249
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Randomized placebo-controlled and controlled non-inferiority phase III trials comparing trafermin, a recombinant human fibroblast growth factor 2, and enamel matrix derivative in periodontal regeneration in intrabony defects. (2016)
  • Author(s): Kitamura M, Akamatsu M, Kawanami M, Furuichi Y, Fujii T, Mori M, Kunimatsu K, Shimauchi H, Ogata Y （他27名）
  • Journal Title: J Bone Miner Res Volume: 31 Issue: 4 Pages: 806-814
  • DOI: 10.1002/jbmr.2738
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Presentation] 広汎型慢性歯周炎患者に歯周外科と自家歯牙移植により天然歯と咬合の保全に努めた一症例 (2017)
  • Author(s): 白方良典, 野口和行
  • Organizer: 第60回春季日本歯周病学会学術大会
• [Presentation] A comparative study of the effects of recombinant human bone morphogenetic protein-2 and -9 on bone formation in rat calvarial critical size defects. (2017)
  • Author(s): Toshiaki Nakamura, Yoshinori Shirakata, Yukiya Shinohara, RJ Miron, Kozue Hasegawa-Nakamura, Kazuyuki Noguchi
  • Organizer: Osteology Japan
  • Int'l Joint Research
• [Presentation] 糖代謝異常を有する切迫早産妊婦の絨毛膜組織での歯周病原細菌の検出 (2017)
  • Author(s): 長谷川梢，中村利明，上塘正人，立石ふみ，橋口千琴，川俣和弥，波多江正紀，野口和行
  • Organizer: 平成29年度日本歯周病学会九州五大学・日本臨床歯周病学会九州支部合同研修会
• [Presentation] Healing of two-wall intrabony defects following treatment with a novel enamel matrix derivative formulation (Osteogain). A preclinical study in non-human primates (2016)
  • Author(s): Y Shirakata, T Nakamura, RJ Miron, Y Shinohara, K Sena, K Noguchi, A Sculean
  • Organizer: 2nd International Symposium Regeneration and Esthetics in Periodontology and Implant Dentistry
  • Place of Presentation: Bern（Switzerland）
  • Year and Date: 2016-11-18
  • Int'l Joint Research
• [Presentation] 歯周基本治療のための新たな教育用模型の開発 (2016)
  • Author(s): 町頭三保、中村利明、白方良典、中村梢、迫田賢二、瀬名浩太郎、篠原敬哉、橋口千琴、田口洋一郎、梅田誠、野口和行
  • Organizer: 第59回秋季日本歯周病学会学術大会
  • Place of Presentation: 朱鷺メッセ（新潟県・新潟市）
  • Year and Date: 2016-10-07
• [Presentation] IL-1βはヒト歯根膜由来細胞のbone morphogenetic protein-9による骨芽細胞様分化を抑制する (2016)
  • Author(s): 江部由佳梨、中村利明、中村梢、野口和行
  • Organizer: 第59回秋季日本歯周病学会学術大会
  • Place of Presentation: 朱鷺メッセ（新潟県・新潟市）
  • Year and Date: 2016-10-07
• [Presentation] サル根岐部病変Ⅲ度に対するOsteogainと吸収性コラーゲンスポンジを用いた歯周組織再生 (2016)
  • Author(s): 白方良典、瀬名浩太郎、中村利明、篠原敬哉、寳来直人、野口和行
  • Organizer: 第59回秋季日本歯周病学会学術大会
  • Place of Presentation: 朱鷺メッセ（新潟県・新潟市）
  • Year and Date: 2016-10-07
• [Presentation] ラット頭蓋骨欠損におけるrhBMP-9 とrhBMP-2 の骨形成効果に対する比較研究 (2016)
  • Author(s): 中村利明、白方良典、野口和行
  • Organizer: 第46回公益社団法人日本口腔インプラント学会学術大会
  • Place of Presentation: 名古屋国際会議場（愛知県・名古屋市）
  • Year and Date: 2016-09-16
• [Presentation] Regenerative effect of Osteogain in class Ⅲ furcations (2016)
  • Author(s): Y Shirakata, RJ Miron, T Nakamura, K Sena, Y Shinohara, DD Bosshardt, K Noguchi, A Sculean
  • Organizer: The 46th Annual Meeting of the Swiss Society of Periodontology
  • Place of Presentation: Bern（Switzerland）
  • Year and Date: 2016-09-01
  • Int'l Joint Research
• [Presentation] 尋常性天疱瘡による剥離性歯肉病変の一症例 (2016)
  • Author(s): 堂満愛弓、中村利明、野口和行
  • Organizer: 第59回春季日本歯周病学会学術大会
  • Place of Presentation: かごしま県民交流センター（鹿児島県・鹿児島市）
  • Year and Date: 2016-05-20
• [Presentation] Recombinant human bone morphogenetic protein-9/コラーゲン担体がラット頭蓋骨欠損の骨形成に及ぼす影響 (2016)
  • Author(s): 篠原敬哉、中村利明、白方良典、古江きらら、野口和行
  • Organizer: 第59回春季日本歯周病学会学術大会
  • Place of Presentation: かごしま県民交流センター（鹿児島県・鹿児島市）
  • Year and Date: 2016-05-20
• [Presentation] サル２壁性骨欠損における新規エナメルマトリックスデリバティブ（Osteogain）による歯周組織再生効果 (2016)
  • Author(s): 白方良典、篠原敬哉、瀬名浩太郎、中村利明、野口和行
  • Organizer: 平成28年度日本歯周病学会九州五大学・日本臨床歯周病学会九州支部合同研修会
  • Place of Presentation: 長崎県歯科医師会館（長崎県・長崎市）
• [Presentation] Bone morphogenetic protein 9 (BMP9)の歯根膜由来線維芽細胞の機能への影響 (2016)
  • Author(s): 古江きらら、瀬名こうたろう、中村利明、迫田賢二、野口和行
  • Organizer: 平成28年度日本歯周病学会九州五大学・日本臨床歯周病学会九州支部合同研修会
  • Place of Presentation: 長崎県歯科医師会館（長崎県・長崎市）