Mechanistic analysis of onset and progress of periodontitis causing microRNA

• Project/Area Number: 25463229
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Periodontology
• Research Institution: Nihon University
• Principal Investigator: OGATA Yorimasa 日本大学, 松戸歯学部, 教授 (90204065)
• Co-Investigator(Kenkyū-buntansha): NAKAYAMA Yohei 日本大学, 松戸歯学部, 専任講師 (30434088) ; TAKAI Hideki 日本大学, 松戸歯学部, 専任講師 (30453898)
• Research Collaborator: MATSUMURA Hiroyoshi ; MATSUI Sari ; KATO Ayako
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000); Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2013: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: microRNA / サイトカイン / 遺伝子発現 / タンパク質発現 / 歯肉線維芽細胞 / 炎症 / 歯周炎 / miRNA / 歯周病 / 炎症性サイトカイン / IL-1 / IL-6 / MKP-5 / IKKα / miR-223 / 歯肉 / 結合組織 / 上皮

Outline of Final Research Achievements

MicroRNAs (miRNAs) can bind to target mRNAs through partial complementarity and regulate many genes. To determine the effects of miR-223 on the expressions of IL-1β and IL-6, HGF were stimulated by IL-1β (1 ng/mL) or TNFα (10 ng/mL) and transfected with a miR-223 expression plasmid. Levels of mRNA for IL-1β, IL-6, inhibitor of kappa-B kinase α (IKKα) and mitogen-activated protein kinase phosphatase-5 (MKP-5) were measured by real-time PCR, and levels IL-1β, IL-6 and IKKα protein were determined by enzyme-linked immunosorbent assay and Western blotting. Expression of IL-1β and IL-6 mRNAs was induced by IL-1β and TNFα and further increased by miR-223 overexpression. IL-1β and TNFα induced the expression of IL-1β and IL-6 mRNAs, and this was reduced by miR-223 inhibitor. Overexpression of miR-223 decreased the levels of IKKα protein and MKP-5 mRNA in HGF. These findings indicate that miR-223 might control the inflammatory response via IKKα and MKP-5 in periodontal tissue.

Research Products

• [Journal Article] Insulin-like growth factor-II regulates bone sialoprotein gene transcription. (2016)
  • Author(s): Choe J, Sasaki Y, Zhou L, Takai H, Nakayama Y, Ogata Y
  • Journal Title: Odontology Volume: 104
  • Peer Reviewed / Open Access / 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
• [Journal Article] Salivary pathogen and serum antibody to assess the progression of chronic periodontitis: a 24-mo prospective multicenter cohort study (2016)
  • Author(s): Morozumi T, Nakagawa T, Nomura Y, Sugaya T, Kawanami M, Suzuki F, Takahashi K, Abe Y, Sato S, Makino-Oi A, Saito A, Takano S, Minabe M, Nakayama Y, Ogata Y, Kobayashi H, Izumi Y, Sugano N, …., Yoshimura A, Hara Y, ….
  • Journal Title: Journal of Periodontal Research Volume: 印刷中 Issue: 6 Pages: 768-778
  • DOI: 10.1111/jre.12353
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Effects of miR-223 on expression of IL-1β and IL-6 in human gingival fibroblasts (2016)
  • Author(s): Matsui S, Ogata Y
  • Journal Title: Journal of Oral Science Volume: 58 Issue: 1 Pages: 101-108
  • DOI: 10.2334/josnusd.58.101
  • NAID: 130005139521
  • ISSN: 1343-4934, 1880-4926
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Effects of an ascorbic Acid-derivative dentifrice in patients with gingivitis: a double-masked, randomized, controlled clinical trial (2015)
  • Author(s): Shimabukuro Y, Nakayama Y, Ogata Y, Tamazawa K, Shimauchi H, Nishida T, Ito K, Chikazawa T, Kataoka S, Murakami S
  • Journal Title: J Periodontol Volume: 86 Issue: 1 Pages: 27-35
  • DOI: 10.1902/jop.2014.140138
  • Peer Reviewed / Open Access
• [Journal Article] Effects of initial periodontal therapy on interleukin-1β level in gingival crevicular fluid and clinical periodontal parameters (2015)
  • Author(s): Oh H, Hirano J, Takai H, Ogata Y
  • Journal Title: Journal of Oral Science Volume: 57 Issue: 2 Pages: 67-71
  • DOI: 10.2334/josnusd.57.67
  • NAID: 130005076037
  • ISSN: 1343-4934, 1880-4926
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Evaluation of a novel immunochromatographic device for rapid and accurate clinical detection of Porphyromonas gingivalis in subgingival plaque (2015)
  • Author(s): Imamura K, Takayama S, Saito A, Inoue E, Nakayama Y, Ogata Y, Shirakawa S, Nagano T, Gomi K, Morozumi T, Akiishi K, Watanabe K, Yoshie H
  • Journal Title: Journal of Microbiological Methods Volume: 117 Pages: 4-10
  • DOI: 10.1016/j.mimet.2015.07.002
  • Peer Reviewed / Open Access
• [Journal Article] Prevalence and quantitative analysis of Epstein - Barr virus DNA and Porphyromonas gingivalis associated with Japanese chronic periodontitis patients (2015)
  • Author(s): Kato A, Imai K, Ochiai K, Ogata Y
  • Journal Title: Clin Oral Invest Volume: 19 Issue: 7 Pages: 1-6
  • DOI: 10.1007/s00784-014-1387-y
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Transcriptional regulation of amelotin gene by proinflammatory cytokines in gingival fibroblasts. (2014)
  • Author(s): Nakayama Y, Takai H, Matsui S, Zhou L, Abiko Y, Ganss B, Ogata Y.
  • Journal Title: Connect Tissue Res Volume: 55 Suppl 1 Issue: sup1 Pages: 18-20
  • DOI: 10.3109/03008207.2014.923848
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] MicroRNA expression in inflamed and noninflamed gingival tissues from Japanese patients (2014)
  • Author(s): Ogata Y, Matsui S, Kato A, Zhou L, Nakayama Y, Takai H
  • Journal Title: J Oral Sci Volume: 56 Pages: 253-260
  • NAID: 130004705234
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Proinflammatory cytokines induce amelotin transcription in human gingival fibroblasts (2014)
  • Author(s): Nakayama Y, Takai H, Matsui S, Matsumura H, Zhou L, Kato A, Bernhard Ganss B, Ogata Y
  • Journal Title: Journal of Oral Science Volume: 56 Issue: 4 Pages: 261-268
  • DOI: 10.2334/josnusd.56.261
  • NAID: 130004705235
  • ISSN: 1343-4934, 1880-4926
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Effects of Thalidomide on Bone Sialoprotein Gene Transcription (2014)
  • Author(s): Kim KM, Wang Z, Kato A, Ogata Y
  • Journal Title: Int J Oral-Med Sci Volume: 13 Pages: 35-44
  • NAID: 130005130353
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Melatonin regulates human bone sialoprotein gene transcription (2014)
  • Author(s): H. Matsumura, Y. Ogata
  • Journal Title: J Oral Science Volume: 56 Pages: 67-76
  • NAID: 130003393080
  • Peer Reviewed
• [Journal Article] Unliganded estrogen receptor alpha stimulates bone sialoprotein gene expression. (2014)
  • Author(s): H. Takai, H. Matsumura, S. Matsui, KM. Kim, M. Mezawa, Y. Nakayama, Y. Ogata
  • Journal Title: Gene Volume: 539 Issue: 1 Pages: 50-57
  • DOI: 10.1016/j.gene.2014.01.063
  • Peer Reviewed
• [Journal Article] Effects of interleukin-11 on the expression of human bone sialoprotein gene (2014)
  • Author(s): H. Matsumura, Y. Nakayama, H. Takai, Y. Ogata
  • Journal Title: J Bone Miner Metab Volume: 32 Issue: 2 Pages: 1-12
  • DOI: 10.1007/s00774-014-0576-8
  • Peer Reviewed
• [Journal Article] Higher prevalence of Epstein-Barr virus DNA in deeper periodontal pockets of chronic periodontitis in Japanese patients (2013)
  • Author(s): Kato A, Imai K, Ochiai K, Ogata Y
  • Journal Title: PLOS ONE Volume: 8 Issue: 8 Pages: 1-5
  • DOI: 10.1371/journal.pone.0071990
  • Peer Reviewed
• [Journal Article] Osteogenic transcription factors and proto-oncogene regulate bone sialoprotein gene transcription (2013)
  • Author(s): H. Takai, M. Mezawa, J. Choe, Y. Nakayama, Y. Ogata
  • Journal Title: J Oral Science Volume: 55 Pages: 209-215
  • NAID: 130003366676
  • Peer Reviewed
• [Journal Article] Forskolin regulates bone sialoprotein gene expression in human breast cancer cells (2013)
  • Author(s): H. Kaneko, D. Kim, Y. Ogata
  • Journal Title: Int J Oral-Med Sci Volume: 12 Pages: 196-203
  • NAID: 130003395901
  • Peer Reviewed
• [Presentation] ヒト歯肉線維芽細胞での炎症性サイトカイン発現に対するmicroRNAの影響． (2015)
  • Author(s): 松井沙莉、能田佳祐、小方頼昌
  • Organizer: 日本歯科保存学会2015年度秋季学術大会（第143回）
  • Place of Presentation: 文京シビックホール（東京都文京区）
  • Year and Date: 2015-11-12
• [Presentation] MicroRNA-223 regulates inflammatory cytokines in human gingival fibroblasts. (2015)
  • Author(s): Sari Matsui, Ayako Kato, Yorimasa Ogata
  • Organizer: Japanese Association for Dental Research
  • Place of Presentation: 福岡国際会議場（福岡県福岡市）
  • Year and Date: 2015-10-30
• [Presentation] Effects of miRNAs on the expression of inflammatory cytokines in human gingival fibroblasts. (2015)
  • Author(s): Sari Matsui, Hideki Takai and Yorimasa Ogata
  • Organizer: EuroPerio8
  • Place of Presentation: London （England）
  • Year and Date: 2015-06-03
• [Presentation] 慢性歯周炎歯肉で発現が増加したmiR-223による炎症性サイトカイン発現の調節． (2015)
  • Author(s): 松井沙莉、高井英樹、小方頼昌
  • Organizer: 第58回春季日本歯周病学会学術大会
  • Place of Presentation: 幕張メッセ（千葉県千葉市）
  • Year and Date: 2015-05-15
• [Presentation] Regulation of Amelotin gene transcription by Proinflammatory Cytokines in Gingival Fibroblasts (2014)
  • Author(s): Nakayama Y, Takai H, Matsui S, Zhou L, Abiko Y, Ganss B, Ogata Y
  • Organizer: 54th General Session of Korean Academy of Periodontology
  • Place of Presentation: Seoul
  • Year and Date: 2014-10-25 – 2014-10-26
• [Presentation] Melatonin Stimulates Human Bone Sialoprotein Gene Expression (2014)
  • Author(s): Matsumura H, Ogata Y
  • Organizer: 92nd General Session & Exhibition of the IADR
  • Place of Presentation: Cape Town, South Africa
  • Year and Date: 2014-06-25 – 2014-06-28
  • Invited
• [Presentation] Effects of Osteogenic Transcription Factors and Proto-oncogene on Bone Sialoprotein Gene Transcription (2014)
  • Author(s): Takai H, Mezawa M, Nakayama Y, Ogata Y
  • Organizer: 92nd General Session & Exhibition of the IADR
  • Place of Presentation: Cape Town, South Africa
  • Year and Date: 2014-06-25 – 2014-06-28
  • Invited
• [Presentation] Inhibition of stem cell-specific transcription factors induces differentiation of preosteoblasts. (2013)
  • Author(s): Ｈ. Takai ＡＪ. van Wijnen, Y. Ogata
  • Organizer: IADR-APR 2013
  • Place of Presentation: Bangkok,Thailand
• [Presentation] Melatonin Regulates Human Bone Sialoprotein Gene Transcription. (2013)
  • Author(s): Ｈ. Matsumura, Y. Nakayama, H. Takai, Y. Ogata
  • Organizer: IADR-APR 2013
  • Place of Presentation: Bangkok,Thailand
• [Presentation] Proinflammatory Cytokines Induce Amelotin Transcription in Human Gingival Fibroblasts. (2013)
  • Author(s): Y. Nakayama, H. Takai, S. Matsui, L. Zhou, Y. Abiko, B. Ganss, Y. Ogata
  • Organizer: 11th ICCBMT
  • Place of Presentation: Wisconsin, USA