The development for disrase model with periodontitis induced by Cytolethal Distending lbxin derived periodontal pathogens, and application of the model to periodontitis prevention

• Project/Area Number: 18592285
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Social dentistry
• Research Institution: Kyushu University (2007); Kyushu Dental College (2006)
• Principal Investigator: AKIFUSA Sumio Kyushu University, Faculty of Dental Science, Department Preventive Dentistry, Assistant Professor (40295861)
• Co-Investigator(Kenkyū-buntansha): ANSAI Toshiro Kyushu Dental College, Department of Health Promotion, Associate Professor (80244789) ; TAKEHARA Tadamichi Kyushu Dental College, Department of Health Promotion, Professor (00038879) ; NISHIHARA Tatsuji Kyushu Dental College, Department of Health Promotion, Professor (80192251)
• Project Period (FY): 2006 – 2007
• Project Status: Completed (Fiscal Year 2007)
• Budget Amount: ¥3,620,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥420,000); Fiscal Year 2007: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2006: ¥1,800,000 (Direct Cost: ¥1,800,000)
• Keywords: periodontitis / Actinobacillus actinomvicetemcomitans / Cvtolethal distending toxin / sonoporation

Research Abstract

It is implied that major cause of tooth loss would be periodontitis in Japanese adolescents. Study on the relationship between oral condition and systemic condition in elderly people revealed that the lowest number of chewable foods were associated with higher risk of mortality than those with the ability to chew all of the 15 types of food surveyed [hazard ratio (BR) = 2.38, 95% confidence interval (95% CI) = 1.07-5.29], though other parameters including current smoking, low serum albumin, and poor physical health status were more significant.Further, reduced chewing ability of soft foods increased the risk (HR = 2.65, 95% CI = 1.20-5.87). Thses evidences suggested that chewing ability was associated with mortality in elderly and may be a predictor for survival rate. Recently, ultrasound-targeting microbubble destruction has been employed in molecular gene therapy, and a new potent nonviral gene transfer method known as 'sonoporation' has been developed. We investigated the efficiency of sonoporation toward growth inhibition of human gingival squamous carcinoma cell line, Ca9-22, in vitro and in vivo. We found that the delivery of BLM by sonoporation induced cytotoxic effect toward Ca9-22 cells in vitro. Our in vivo results showed that tumors nearly disappeared in Ca9-22 cell-implanted nude KSN/slc mice treated with a low dose of BLM followed by sonoporation during the 4-week experimental period. We previously reported that the cytolethal distending toxin B(cdtB)from Actinobacallus actinomycetemcnmitans a periodontopathic bacterium, is responsible for cell cycle arrest and apoptosis in vitro. Thus, we used sonoporation to transfect a cdtB-expressing plasmid into Ca9-22 cells and examined cell viability in vitro and in vivo. We found that an administration of cdtB-expressing plasmid followed by sonoporation-induced marked growth inhibition of Ca9-22 cells and apoptotic cells were also observed in vitro and in vivo.

Research Products

• [Journal Article] Local delivery system of cytotoxic agents to tumors by focused sonoporation (2007)
  • Author(s): Iwanaga K, et. al.
  • Journal Title: Cancer Gene Therapy 14 Pages: 354-363
  • Description: 「研究成果報告書概要(和文)」より
  • Peer Reviewed
• [Journal Article] Relationship between chewing ability and 4-year mortality in acohort of 80-year-old Japanese people (2007)
  • Author(s): Ansai T, et. al.
  • Journal Title: Oral Disease 13 Pages: 214-219
  • Description: 「研究成果報告書概要(和文)」より
  • Peer Reviewed
• [Journal Article] Potential role of high molecular weight hyaluronan in the anti-Candida activity of human oral epithelial cells (2007)
  • Author(s): Sakai A, et. al.
  • Journal Title: Medical Mycology 45 Pages: 73-79
  • Description: 「研究成果報告書概要(和文)」より
  • Peer Reviewed
• [Journal Article] High-level functional capacity and 4-year mortality in an 80-year-old population (2007)
  • Author(s): Takata Y, et. al.
  • Journal Title: Gerontology 53 Pages: 46-51
  • Description: 「研究成果報告書概要(和文)」より
  • Peer Reviewed
• [Journal Article] Association between body mass index and mortality in an 80-year-old population (2007)
  • Author(s): Takata Y, et. al.
  • Journal Title: Journal of American Geriatric Society 55 Pages: 931-917
  • Description: 「研究成果報告書概要(和文)」より
  • Peer Reviewed
• [Journal Article] Physical fitness and 4-year mortality in an 80-year-old population (2007)
  • Author(s): Takata Y, et. al.
  • Journal Title: Journal of Gerontology 62 Pages: 851-858
  • Description: 「研究成果報告書概要(和文)」より
  • Peer Reviewed
• [Journal Article] Hyperglycemia promotes microinflammation as evaluated by C-reactive protein in the very elderly (2007)
  • Author(s): Fukuhara M, et. al.
  • Journal Title: Internal Medicine 46 Pages: 207-212
  • Description: 「研究成果報告書概要(和文)」より
  • Peer Reviewed
• [Journal Article] Potential role of high molecular weight hyaluronan in the anti-Candida activity of human oral epithelial cells (2007)
  • Author(s): Sakai, A., Akifusa, S., Itano, N., Kimata, K., Kawamura, T., Koseki, T., Takehara, T., NishiharaT
  • Journal Title: Medical Mycology 45 Pages: 73-79
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Relationship between chewing ability and 4-year mortality in a cohort of 80-year-old Japanese people (2007)
  • Author(s): Ansai, T., Takata, Y., Soh, I., Akifusa, S., Sogame, A.,Shimada, N.,Yoshida, A.,Hamasaki, T., Awano,S., Fukuhara, M., Takehara T
  • Journal Title: Oral Disease 13 Pages: 214-219
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Local delivery system of cytotoxic agents to tumors by focused sonoporation (2007)
  • Author(s): Iwanaga,K., Tominaga, K., Yamamoto, K., Habu, M., Maeda, H., Akifusa, S., Tsujisawa, T., Okinaga, T., Fukuda, J., NishiharaT
  • Journal Title: Cancer Gene Therapy 14 Pages: 354-363
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] High-level functional capacity and 4-year mortality in an 80-year-old population (2007)
  • Author(s): Takata,Y., Ansai, T.,Akifusa, S., Soh,I., Sonoki, K., Takehara T
  • Journal Title: Gerontology 53 Pages: 46-51
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Association between body mass index and mortality in an 80-year-old population (2007)
  • Author(s): Takata,Y., Ansai, T., Soh, I., Akifusa,S., Sonoki, K., Fujisawa, K., Awano,S., Kagiyama,S., Hamasaki, T., ,Nakamichi, I., Yoshida,A., Takehara T
  • Journal Title: Journal of American Geriatric Society 55 Pages: 913-917
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Physical fitness and 4-year mortality in an 80-year-old population (2007)
  • Author(s): Takata,Y., Ansai,T., Akifusa, S., Soh,I., Yoshitake,Y., Kimura,Y., Sonoki,K., Fujisawa, K., Awano,S., Kagiyama, S., Hamasaki,T., Nakamichi, I., Yoshida, A., Takehara T
  • Journal Title: Journal of Gerontology 62 Pages: 851-858
  • NAID: 110006453305
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Hyperglycemia promotes microinflammation as evaluated by C-reactive protein in the very elderly (2007)
  • Author(s): Fukuhara, M., Matsumura, K., Wakisaka, M., Takata, Y., Sonoki, K., Fujisawa, K., Ansai, T., Akifusa, S., Fujii, K., Iida, M., Takehara T
  • Journal Title: Internal Medicine 46 Pages: 207-212
  • NAID: 130000078552
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Relationship between chewing ability and 4-year mortality in a cohort of 80-year-old Japanese people (2007)
  • Author(s): Ansai T, et. al.
  • Journal Title: Oral Disease 13 Pages: 214-219
  • Peer Reviewed
• [Journal Article] Potential role of high molecular weight hyaluronan in the antivity of human oral epithelial cells (2007)
  • Author(s): Sakai A, et. al.
  • Journal Title: Medical Mycology 45 Pages: 73-79
  • Peer Reviewed
• [Journal Article] Local delivery system of cytotoxic agents to tumors by focused sonoporation. (2007)
  • Author(s): Iwanaga K, Tomonaga K, Yamamoto K, Habu M, Maeda H, Akifusa S. et al.
  • Journal Title: Cancer Gene Therapy
• [Journal Article] Chewing ability and quahty of life in an 80-year-old population (2006)
  • Author(s): Takata Y, et. al.
  • Journal Title: Journal of Oral Rehabilitation 33 Pages: 330-334
  • Description: 「研究成果報告書概要(和文)」より
  • Peer Reviewed
• [Journal Article] Prediction of cognitive function by arterial stiffness in the very elderly (2006)
  • Author(s): Fukuhara M, et. al.
  • Journal Title: Circulation Journal 70 Pages: 756-761
  • Description: 「研究成果報告書概要(和文)」より
  • Peer Reviewed
• [Journal Article] Prevalence of periodontopathic bacteria on the tongue dorsum of elderly people (2006)
  • Author(s): Tachibana M, et. al.
  • Journal Title: Gerodontology 23 Pages: 123-126
  • Description: 「研究成果報告書概要(和文)」より
  • Peer Reviewed
• [Journal Article] Chewing ability and quality of life in an 80-year-old population (2006)
  • Author(s): Takata,Y., Ansai, T., Awano, S.,Fukuhara, M., Sonoki, K., Wakisaka, M.,Fujisawa, K., Akifusa,S., TakeharaT.
  • Journal Title: Journal of Oral Rehabilitation 33 Pages: 330-334
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Prediction of cognitive function by arterial stiffness in the very elderly (2006)
  • Author(s): Fukuhara,M., Matsumura, K., Ansai, T., Takata, Y., Sonoki, K., Akifusa,S., Wakisaka,M., Hamasaki,T., Fujisawa,K., Yoshida,A., Fujii,K., Iida, M., TakeharaT
  • Journal Title: Circulation Journal 70 Pages: 756-761
  • NAID: 110004750154
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Prevalence of periodontopathic bacteria on the tongue dorsum of elderly people (2006)
  • Author(s): Tachibana,M., Yoshida,A., Ansai, T., Takata, Y., Akifusa, S., Fukuhara,M., Hamasaki, T., Okuda,K., TakeharaT
  • Journal Title: Gerodontology 23 Pages: 123-126
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Prediction of cognitive function by arterial stiffness in the very elderly. (2006)
  • Author(s): Fukuhara M., Matsumura K., Ansai T., Takata Y., Sonoki K., Akifusa S., et al.
  • Journal Title: Circulation Journal 70・6 Pages: 756-761
  • NAID: 110004750154
• [Journal Article] Prevalence of periodontopathic bacteria on the tongue dorsum of elderly people. (2006)
  • Author(s): Tachibana M., Yoshida A., Ansai T., Takata Y., Akifusa S., et al.
  • Journal Title: Gerodontology 23・2 Pages: 123-126
• [Journal Article] Chewing ability and quality of life in an 80-year-old population. (2006)
  • Author(s): Takata Y., Ansai T., Awano S., Fukuhara M., Sonoki K., Wakisaka M., Fujisawa K., Akifusa S., et al.
  • Journal Title: Journal of Oral Rehabilitation 33・5 Pages: 330-334