Elucidation of mechanism for development of cerebrovascular diseases associated with oral bacteria and pursuit of preventive approach

• Project/Area Number: 21689052
• Research Category: Grant-in-Aid for Young Scientists (A)
• Allocation Type: Single-year Grants
• Research Field: Orthodontic/Pediatric dentistry
• Research Institution: Osaka University
• Principal Investigator: NAKANO Kazuhiko 大阪大学, 歯学研究科, 准教授 (00379083)
• Research Collaborator: OOSHIMA Takashi 大阪大学, 歯学研究科, 教授 (80116003) ; UMEMURA Kazuo 浜松医科大学, 医学部, 教授 (40232912) ; TANAKA Tokutaro 聖隷浜松病院, 脳神経外科, 部長 (90283366)
• Project Period (FY): 2009 – 2011
• Project Status: Completed (Fiscal Year 2011)
• Budget Amount: ¥26,260,000 (Direct Cost: ¥20,200,000、Indirect Cost: ¥6,060,000); Fiscal Year 2011: ¥5,720,000 (Direct Cost: ¥4,400,000、Indirect Cost: ¥1,320,000); Fiscal Year 2010: ¥8,840,000 (Direct Cost: ¥6,800,000、Indirect Cost: ¥2,040,000); Fiscal Year 2009: ¥11,700,000 (Direct Cost: ¥9,000,000、Indirect Cost: ¥2,700,000)
• Keywords: 口腔レンサ球菌 / 感染性心内膜炎 / 分子生物学 / 心臓弁 / 歯垢 / 口腔細菌 / 脳血管疾患 / う蝕原性細菌 / コラーゲン結合タンパク / 血小板凝集 / 血管内皮 / 表層電荷 / 唾液 / 脳出血 / Streptococcus mutans / マウスモデル / Staphylococcus aureus / 脳血管障害 / 血小板凝集能 / 菌血症

Research Abstract

Infection with specific strains of Streptococcus mutans, a pathogen of dental caries, by injection into the jugular veins of mice with a photochemically-injured middle cerebral artery resulted in cerebral hemorrhage development. These S. mutans strains possess a 120-kDa collagen-binding protein(Cnm protein) on the cell surface, which inhibits platelet aggregation properties. In addition, the detection rate of Cnm-positive S. mutans strains in patients with a cerebral hemorrhage has been found to be significantly higher than that in healthy individuals.

Research Products

• [Journal Article] Distribution of oral streptococci highly resistant to amoxicillin in dental plaque specimens from Japanese children and adolescents (2011)
  • Author(s): Nemoto H, Nakano K, Masuda K, Wada K, Ardin AC, Nomura R, Ooshima T
  • Journal Title: J Med Microbiol Volume: 60 Pages: 1853-1859
  • Peer Reviewed
• [Journal Article] Multilocus sequence typing analysis of Streptococcus mutans strains with the cnm gene encoding a collagen-binding adhesin (2011)
  • Author(s): Lapirattanakul J, Nakano K, Nomura R, Leelataweewud P, Chalermsarp N, Klaophimai A, Srisatjaluk R, Hamada S, Ooshima T
  • Journal Title: J Med Microbiol Volume: 60 Pages: 1677-1684
  • Peer Reviewed
• [Journal Article] The collagen-binding protein of Streptococcus mutans is involved in haemorrhagic stroke (2011)
  • Author(s): Nakano K, Hokamura K, Taniguchi N, Wada K, Kudo C, Nomura R, Kojima A, Naka S, Muranaka Y, Thura M, Nakajima A, Masuda K, Speziale P, Shimada N, Amano A, Kamisaki Y, Tanaka T, Umemura K, Ooshima T
  • Journal Title: Nat Commun Volume: 2 Pages: 485-485
  • Peer Reviewed
• [Journal Article] Isolation and characterization of Streptococcus mitis from blood of child with osteomyelitis (2011)
  • Author(s): Nomura R, Nakano K, Makela K, Vaara M, Salo E, Alaluusua S, Ooshima T
  • Journal Title: Int J Paediatr Dent Volume: 21 Pages: 192-199
  • Peer Reviewed
• [Journal Article] Characterization of aortic aneurysm of cardiovascular diseases patients harboring Porphyromonas gingivalis (2011)
  • Author(s): Nakano K, Wada K, Nomura R, Nemoto H, Inaba H, Kojima A, Naka S, Hokamura K, Mukai T, Hata H, Toda K, Nakajima A, Umemura K, Kamisaki Y, Yoshioka H, Taniguchi K, Amano A, Ooshima T
  • Journal Title: Oral Dis Volume: 17 Pages: 371-378
  • Peer Reviewed
• [Journal Article] Common knowledge regarding prevention of infective endocarditis among general dentists in Japan (2011)
  • Author(s): Nakano K, Ooshima T
  • Journal Title: J Cardiol Volume: 57 Pages: 123-130
  • NAID: 10027869585
  • Peer Reviewed
• [Journal Article] The collagen-binding protein of Streptococcus mutans is involved in hemorrhagic stroke (2011)
  • Author(s): Nakano K, Hokamura K, Taniguchi N, Wada K, Kudo C, Nomura R, Kojima A, Naka S, Muranaka Y, Thura M, Nakajima A, Masuda K, Nakagawa I, Speziale P, Shimada N, Amano A, Kamisaki Y, Tanaka T, Umemura K, Ooshima T.
  • Journal Title: Nature Communications Volume: 2 Issue: 1 Pages: 485-485
  • DOI: 10.1038/ncomms1491
  • Peer Reviewed
• [Journal Article] Common knowledge regarding prevention of infective endocarditis among general dentists in Japan. (2011)
  • Author(s): Nakano K, Ooshima T.
  • Journal Title: Journal of Cardiology Volume: 57 Pages: 123-130
  • NAID: 10027869585
  • Peer Reviewed
• [Journal Article] Detection of oral streptococci with collagen-binding properties in saliva specimens from mothers and their children (2010)
  • Author(s): Nomura R, Naka S, Nakano K, Taniguchi N, Matsumoto M, Ooshima T
  • Journal Title: Int J Paediatr Dent Volume: 20 Pages: 254-260
  • Peer Reviewed
• [Journal Article] Defect of glucosyltransferases reduces platelet aggregation activity of Streptococcus mutans : Analysis of clinical strains isolated from oral cavities (2010)
  • Author(s): Taniguchi N, Nakano K, Nomura R, Naka S, Kojima A, Matsumoto M, Ooshima T
  • Journal Title: Arch Oral Biol Volume: 55 Pages: 410-416
  • Peer Reviewed
• [Journal Article] Molecular analysis of aortic intimal hyperplasia caused by Porphyromonas gingivalis infection in mice with endothelial damage (2010)
  • Author(s): Hokamura K*, Inaba H*, Nakano K*, Nomura R, Yoshioka H, Taniguchi K, Ooshima T, Wada K, Amano A, Umemura K
  • Journal Title: J Periodontal Res Volume: 45 Pages: 337-344
  • Peer Reviewed
• [Journal Article] Molecular characterization of Streptococcus mutans strains containing the cnm gene encoding a collagen-binding adhesin (2010)
  • Author(s): Nakano K, Nomura R, Taniguchi N, Lapirattanakul J, Kojima A, Naka S, Senawongse P, Srisatjaluk R, Gronroos L, Alaluusua S, Matsumoto M, Ooshima T
  • Journal Title: Arch Oral Biol Volume: 55 Pages: 34-39
  • Peer Reviewed
• [Journal Article] Molecular characterization of Streptococcus mutans clinical strains with gene encoding collagen-binding adhesin. (2010)
  • Author(s): Nakano K, et al.
  • Journal Title: Archives of Oral Biology Volume: 55 Pages: 34-39
  • Peer Reviewed
• [Journal Article] Molecular analysis of aortic intimal hyperplasia caused by Porphyromonas gingivalis infection in mice with endothelial damage. (2010)
  • Author(s): Nakano K, et al.
  • Journal Title: Journal of Periodontal Research Volume: 45 Pages: 337-344
  • Peer Reviewed
• [Journal Article] Detection of oral streptococci with collagen-binding properties in saliva specimens from mothers and their children. (2010)
  • Author(s): Nomura R, Naka S, Nakano K, et al.
  • Journal Title: International Journal of Paediatric Dentistry (In press)
  • Peer Reviewed
• [Journal Article] Detection of serotype k Streptococcus mutans in Thai subjects (2009)
  • Author(s): Lapirattanakul J, Nakano K, Nomura R, Nemoto H, Kojima A, Senawongse P, Srisatjaluk R, Ooshima T
  • Journal Title: Oral Microbiol Immunol Volume: 24 Pages: 431-433
  • Peer Reviewed
• [Journal Article] Comparative genomic analyses of Streptococcus mutans provide insights into chromosomal shuffling and species-specific content (2009)
  • Author(s): Maruyama F, Kobata M, Kurokawa K, Nishida K, Sakurai A, Nakano K, Nomura R, Kawabata S, Ooshima T, Nakai K, Hattori M, Hamada S, Nakagawa I
  • Journal Title: BMC Genomics Volume: 10 Pages: 358-358
  • Peer Reviewed
• [Journal Article] Molecular and clinical analyses of the gene encoding collagen-binding adhesin of Streptococcus mutans (2009)
  • Author(s): Nomura R, Nakano K, Tanigichi N, Lapirattanakul J, Nemoto H, Gronroos L, Alaluusua S, Ooshima T
  • Journal Title: J Med Microbiol Volume: 58 Pages: 469-475
  • Peer Reviewed
• [Journal Article] Upregulation of S100 calcium-binding protein A9 is required for induction of smooth muscle cell proliferation by a periodontal pathogen (2009)
  • Author(s): Inaba H*, Hokamura K*, Nakano K*, Nomura R, Katayama K, Nakajima A, Yoshioka H, Taniguchi K, Kamisaki Y, Ooshima T, Umemura K, Murad F, Wada K, Amano A
  • Journal Title: FEBS Lett Volume: 583 Pages: 128-134
  • Peer Reviewed
• [Journal Article] Detection of oral bacteria in cardiovascular specimens (2009)
  • Author(s): Nakano K, Nemoto H, Nomura R, Inaba H, Yoshioka H, Taniguchi K, Amano A, Ooshima T
  • Journal Title: Oral Microbiol Immunol Volume: 24 Pages: 64-68
  • Peer Reviewed
• [Journal Article] Molecular analyses of bacterial DNA in extirpated heart valves from infective endocarditis patients (2009)
  • Author(s): Nomura R, Nakano K, Nemoto H, Mukai T, Hata H, Toda K, Yoshioka H, Taniguchi K, Amano A, Ooshima T
  • Journal Title: Oral Microbiol Immunol Volume: 24 Pages: 43-49
  • Peer Reviewed
• [Journal Article] Molecular and clinical analyses of gene encoding collagen-binding adhesin of Streptococcus mutans. (2009)
  • Author(s): Nomura R, Nakano K, Tanigichi N, et al.
  • Journal Title: Journal of Medical Microbiology 58 Pages: 469-475
  • Peer Reviewed
• [Journal Article] Molecular characterization of Streptococcus mutans clinical strains with gene encoding collagen-binding adhesin. (2009)
  • Author(s): Nakano K, Nomura R, Taniguchi N, et al.
  • Journal Title: Archives of Oral Biology 55 Pages: 34-39
  • Peer Reviewed
• [Journal Article] Identification and characterization of a collagen-binding protein, Cbm, in Streptococcus mutans
  • Author(s): Nomura R, Nakano K, Naka S, Nemoto H, Masuda K, Lapirattanakul J, Alaluusua S, Matsumoto M, Kawabata S, Ooshima T
  • Journal Title: Mol Oral Microbiol Volume: (in press)
  • Peer Reviewed
• [Journal Article] Amoxicillinresistant oral streptococci identified in dental plaque specimens from healthy Japanese adults
  • Author(s): Masuda K, Nemoto H, Nakano K, Naka S, Nomura R, Ooshima T
  • Journal Title: J Cardiol Volume: (in press)
  • NAID: 10031187747
  • Peer Reviewed
• [Presentation] Streptococcus mutansのコラーゲン結合タンパクについて (2012)
  • Author(s): 野村良太, 仲野和彦, 仲周平, 大嶋隆
  • Organizer: 第113回大阪大学歯学会例会
  • Place of Presentation: 吹田
  • Year and Date: 2012-01-12
• [Presentation] 脳出血における増悪因子としてのう蝕病原細菌Streptococcus mutans (2011)
  • Author(s): 仲野和彦, 野村良太, 外村和也, 大橋寿彦, 細井泰志, 田中篤太郎, 梅村和夫, 大嶋隆
  • Organizer: 第36回脳卒中学会総会
  • Place of Presentation: 京都
  • Year and Date: 2011-07-31
• [Presentation] 高病原性う蝕原因菌Streptococcus mutansは脳出血を増悪させる (2011)
  • Author(s): 梅村和夫, 外村和也, 仲野和彦, 野村良太, 大嶋隆, 大橋寿彦, 細井泰志, 田中篤太郎
  • Organizer: 第36回脳卒中学会総会
  • Place of Presentation: 京都
  • Year and Date: 2011-07-31
• [Presentation] コラーゲン結合能と血小板凝集抑制能を有する"う蝕"(虫歯)菌は脳卒中のリスクファクターとなり得るか (2011)
  • Author(s): 田中篤太郎, 細井泰志, 大橋寿彦, 外村和也, 梅村和夫, 仲野和彦, 野村良太, 大嶋隆
  • Organizer: 第36回脳卒中学会総会
  • Place of Presentation: 京都
  • Year and Date: 2011-07-31
• [Presentation] コラーゲン結合能と血小板凝集抑制能を有する"う蝕"(虫歯)菌は脳卒中のリスクファクターとなり得るか? (2011)
  • Author(s): 田中篤太郎, ら
  • Organizer: 第36回脳卒中学会総会
  • Place of Presentation: 京都
  • Year and Date: 2011-07-31
• [Presentation] Distribution of Streptococcus mutans strains with collagen-binding activities and their adhesion properties to endothelial cells (2011)
  • Author(s): Nomura R, Nakano K, Naka S, Matsumoto M, Ooshima T
  • Organizer: 59th Congress of European Organization of Caries Research
  • Place of Presentation: Kaunas, Lithuania
  • Year and Date: 2011-07-06
• [Presentation] Distribution of Streptococcus mutans strains with collagen-binding properties (2011)
  • Author(s): Naka S, Nakano K, Nomura R, Ooshima T
  • Organizer: 23rd Meeting of International Association of Paediatric Dentistry
  • Place of Presentation: Athens, Greece
  • Year and Date: 2011-06-15
• [Presentation] Distribution of Streptococcus mutans strains with collagen-binding properties (2011)
  • Author(s): Naka S, Nakano K, Nomura R, Ooshima T
  • Organizer: 23rd meeting of International Association of Paediatric Dentistry
  • Place of Presentation: Athens, Greece
  • Year and Date: 2011-06-15
• [Presentation] Relationship of Streptococcus mutans collagen-binding properties with cerebral hemorrhage deterioration (2011)
  • Author(s): Nakano K, Nomura R, Taniguchi N, Wada K, Ooshima T
  • Organizer: 89th Meeting of International Association of Dental Research
  • Place of Presentation: San Diego, USA
  • Year and Date: 2011-03-16
• [Presentation] Characterization of novel collagen-binding protein of Streptococcus mutans (2011)
  • Author(s): Nomura R, Nakano K, Ooshima T
  • Organizer: 89th Meeting of International Association of Dental Research
  • Place of Presentation: San Diego, USA
  • Year and Date: 2011-03-16
• [Presentation] Relationship of Streptococcus mutans collagen-binding properties with cerebral hemorrhage deterioration. (2011)
  • Author(s): Nakano, et al.
  • Organizer: 89th IADR meeting
  • Place of Presentation: San Diego, USA
  • Year and Date: 2011-03-16
• [Presentation] 感染性心内膜炎予防に対する歯科医師における意識調査 (2010)
  • Author(s): 小島あゆち, 仲野和彦, 野村良太, 大嶋隆
  • Organizer: 第29回日本小児歯科学会近畿地方会
  • Place of Presentation: 枚方市(大阪府)
  • Year and Date: 2010-10-17
• [Presentation] Characterization of aortic aneurysm in patients harboring Porphyromonas gingivalis. (2010)
  • Author(s): Nakano, et al.
  • Organizer: 88th IADR meeting
  • Place of Presentation: Barcelona, Spain
  • Year and Date: 2010-07-14
• [Presentation] Contribution of collagen-binding adhesin of Streptococcus mutans to cause deterioration of cerebral hemorrhage (2010)
  • Author(s): Nomura R, Nakano K, Taniguchi N, Wada K, Matsumoto M, Ooshima T
  • Organizer: 58th Congress of European Organization of Caries Research
  • Place of Presentation: Montpellier, France
  • Year and Date: 2010-07-07
• [Presentation] マウス大脳動脈損傷モデルにおけるStreptococcus mutansコラーゲン結合タンパクの病原性への関与 (2010)
  • Author(s): 谷口奈穂, 仲野和彦, 野村良太, 松本道代, 大嶋隆
  • Organizer: 第48回日本小児歯科学会大会
  • Place of Presentation: 名古屋
  • Year and Date: 2010-05-19
• [Presentation] 小児大腿骨骨髄炎患者血液より分離したStreptococcus mitis株の性状の分析 (2010)
  • Author(s): 野村良太, 仲野和彦, 小島あゆち, 松本道代, 大嶋隆
  • Organizer: 第48回日本小児歯科学会大会
  • Place of Presentation: 名古屋
  • Year and Date: 2010-05-19
• [Presentation] マウス大脳動脈損傷モデルにおけるStreptococcus mutansコラーゲン結合タンパクの病原性への関与 (2010)
  • Author(s): 谷口奈穂, 仲野和彦, 野村良太, 松本道代, 大嶋隆
  • Organizer: 第48回日本小児歯科学会
  • Place of Presentation: 名古屋市(愛知県)
  • Year and Date: 2010-05-19
• [Presentation] 小児唾液中に存在するコラーゲン結合能を有する菌株の分析 (2009)
  • Author(s): 仲周平, 野村良太, 仲野和彦, 大嶋隆
  • Organizer: 第28回日本小児歯科学会近畿地方会大会
  • Place of Presentation: 大阪
  • Year and Date: 2009-10-18
• [Presentation] Streptococcus mutans臨床分離株におけるグルコシルトランスフェラーゼの発現と血小板凝集能への関与 (2009)
  • Author(s): 谷口奈穂, 仲野和彦, 野村良太, 松本道代, 大嶋隆
  • Organizer: 第28回日本小児歯科学会近畿地方会大会
  • Place of Presentation: 大阪
  • Year and Date: 2009-10-18
• [Presentation] 大腿骨骨髄炎を呈した小児の病変部及び口腔から分離した菌株の性状の分析 (2009)
  • Author(s): 小島あゆち, 野村良太, 大川玲奈, 仲野和彦, 大嶋隆
  • Organizer: 第28回日本小児歯科学会近畿地方会大会
  • Place of Presentation: 大阪
  • Year and Date: 2009-10-18
• [Presentation] Genes concerning adhesion to extracellular matrix in Streptococcus mutans from Thai subjects (2009)
  • Author(s): Lapirattanakul J, Nakano K, Senawongse P, Leelataweewud P, Srisatjaluk R, Ooshima T
  • Organizer: 5th Congress of International Dental Collaboration of the Mekong River Region
  • Place of Presentation: Hanoi, Vietnam
  • Year and Date: 2009-10-14
• [Presentation] Streptococcus mutansゲノム解析に基づく種レベルでの進化機構の解析 (2009)
  • Author(s): 中川一路, 仲野和彦, 川端重忠, 大嶋隆, 浜田茂幸
  • Organizer: 第51回日本歯科基礎医学会大会
  • Place of Presentation: 新潟
  • Year and Date: 2009-09-10
• [Presentation] Presence of serotype k strains of Streptococcus mutans is a potential risk factor for cerebral hemorrhage (2009)
  • Author(s): Nakano K, Taniguchi N, Kojima A, Nomura R, Wada K, Ooshima T
  • Organizer: 56th Congress of European Organization of Caries Research
  • Place of Presentation: Budapest, Hung
  • Year and Date: 2009-07-01
• [Presentation] Molecular analyses of Streptococcus mutans strains with collagen-binding properties (2009)
  • Author(s): Nomura R, Nakano K, Taniguchi N, Kojima A, Naka S, Ooshima T
  • Organizer: 56th Congress of European Organization of Caries Research
  • Place of Presentation: Budapest, Hungary
  • Year and Date: 2009-07-01
• [Presentation] Serotype k strains of Streptococcus mutans are potential risk factor to cause cerebral hemorrhage. (2009)
  • Author(s): Nakano K, Taniguchi N, Kojima A, Nomura R, Wada K, Ooshima T.
  • Organizer: 57th ORCA Congress
  • Place of Presentation: Budapest, Hungary
  • Year and Date: 2009-07-01
• [Presentation] Molecular analyses of Streptococcus mutans strains with collagen-binding properties. (2009)
  • Author(s): Nomura R, Nakano K, Taniguchi N, Kojima A, Naka S, Ooshima T.
  • Organizer: 57th ORCA Congress
  • Place of Presentation: Budapest, Hungary
  • Year and Date: 2009-07-01
• [Presentation] 唾液中に含まれる口腔レンサ球菌のコラーゲン結合能に関する分析 (2009)
  • Author(s): 仲周平, 野村良太, 仲野和彦, 大嶋隆
  • Organizer: 第47回日本小児歯科学会大会
  • Place of Presentation: 吹田
  • Year and Date: 2009-05-14
• [Presentation] マウス大脳動脈損傷モデルにおけるS. mutansの病原性の検討 (2009)
  • Author(s): 谷口奈穂, 仲野和彦, 野村良太, 大嶋隆
  • Organizer: 第47回日本小児歯科学会大会
  • Place of Presentation: 吹田
  • Year and Date: 2009-05-14
• [Presentation] 唾液中に含まれる口腔レンサ球菌のコラーゲン結合能に関する分析 (2009)
  • Author(s): 仲周平, 野村良太, 仲野和彦, 大嶋隆
  • Organizer: 第47回日本小児歯科学会大会
  • Place of Presentation: 大阪
  • Year and Date: 2009-05-14
• [Presentation] マウス大脳動脈損傷モデルにおけるS.mutansの病原性の検討 (2009)
  • Author(s): 谷口奈穂, 仲野和彦, 野村良太, 大嶋隆
  • Organizer: 第47回日本小児歯科学会大会
  • Place of Presentation: 大阪
  • Year and Date: 2009-05-14
• [Book] Oral bacteria detected in the hearts of patients with valvular diseases (2010)
  • Author(s): Nakano K, Taniguchi K, Ooshima T
  • Publisher: Nova Science Publishers
• [Book] Oral bacteria detected in the hearts of patients with valvular diseases.In : Bennington EH editor. Horizons in World Cardiovascular Research. Vol.2 (2010)
  • Author(s): Nakano K, Taniguchi K, Ooshima T.
  • Publisher: Nova Science Publishers
• [Remarks]
  • URL: http://web.dent.osaka-u.ac.jp/.pedo/research/index.html
• [Remarks]
  • URL: http://web.dent.osaka-u.ac.jp/~pedo/research/index.html