APEC 2021


Nobuyuki Kawashima

Anti-inflammatory Action of Mineral Trioxide Aggregate; a New Insight


Mineral trioxide aggregate (MTA) is a Portland cement-derived bioactive dental cement that shows favorable clinical outcomes in several endodontic applications, including direct pulp capping, root-end filling, and root perforation repair. MTA possesses excellent biocompatibility and good physical properties including sealing ability and structural stability, as well as the ability to induce formation of reparative mineralized tissues. Recently, several in vitro and in vivo studies have revealed that MTA reduces inflammation by downregulation of pro-inflammatory cytokines. Furthermore, MTA induces macrophage polarization towards the M2 phenotype in vitro, as well as selective recruitment of M2 marker-expressing macrophages in dental pulp and subcutaneous tissue in vivo. This lecture will focus on the anti-inflammatory effects of MTA as a new insight into the mechanisms of action of this material.

Short cv

Name: Nobuyuki Kawashima, DDS, PhD

Affiliation: Department of Pulp Biology and Endodontics, Division of Oral Health Sciences, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University

Email:  kawashima.n.endo@tmd.ac.jp


1986 DDS Faculty of Dentistry, Niigata University

1991 PhD Department of Endodontics, Tokyo Medical and Dental University

Academic/Professional Appointments:

1995-2003 Research Associate of Tokyo Medical and Dental University

2005-2008 Associate Professor of 21st COE Program

2008-2017 Assistant Professor of Tokyo Medical and Dental University

2017-Present Junior Associate Professor of Tokyo Medical and Dental University

Post Doctoral Training:

1996-1998, 2000 Post-Doctoral Fellow, The Forsyth Institute, Boston, MA

Awards and Honors:

2007 Samuel Seltzer Prize: Best Paper Award of OOOOE

Invited Presentations

2016 IADR PBRG Satellite Symposium, June 26-28, Nagoya.

2015 APEC, April 8-10, Le Royal Hotel Amman, Jordan.

2011 APEC, April 21st, Jahad Daneshgahi Complex, Shiraz, Iran.

2005 Dentin/Pulp Complex, Heinrich Heine University, Dusseldorf, Sept 18th-20th.


Original Articles

1. Kawashima.N, Hashimoto K, Kuramoto M, Bakhit A, Wakabayashi Y, Okiji T, A novel bioactive endodontic sealer containing surface-reaction-type prereacted glassionomer filler iduces osteoblast differentiation, Materials. 2020 Oct 9;13(20):4477. 

2. Tazawa K, Kawashima N, Kuramoto M, Noda S, Fujii M, Nara K, Hashimoto K, Okiji T, Transient Receptor Potential Ankyrin 1 Is Up-Regulated in Response to Lipopolysaccharide via P38/Mitogen-Activated Protein Kinase in Dental Pulp Cells and Promotes Mineralization. Am J Pathol. 2020 Dec;190(12):2417-2426. 

3. Kuramoto M, Kawashima N, Tazawa K. Nara K, Fujii M, Noda S, Hashimoto K, Nozaki K, Okiji T, Mineral trioxide aggregate suppresses pro-inflammatory cytokine expression via the calcineurin/nuclear factor of activated T cells/early growth response 2 pathway in lipopolysaccharide-stimulated macrophages, Int Endod J. 2020 Dec;53(12):1653-1665.

4. Fujii M, Kawashima N, Tazawa K, Hashimoto K, Nara K, Noda S, Nagai S, Okiji T. Hypoxia-inducible factor 1α promotes interleukin 1β and tumour necrosis factor α expression in lipopolysaccharide-stimulated human dental pulp cells, Int Endod J. 2020 May;53(5):636-646. 

5. Fujii M, Kawashima N, Tazawa K, Hashimoto K, Nara K, Noda S, Kuramoto M, Orikasa S, Nagai S, Okiji T. HIF1α inhibits LPS-mediated induction of IL-6 synthesis via SOCS3-dependent CEBPβ suppression in human dental pulp cells, Biochem Biophys Res Commun. 2020 Feb 5;522(2):308-314. 

6. Nara K, Kawashima N, Noda S, Fujii M, Hashimoto K, Tazawa K, Okiji T. Anti-inflammatory roles of microRNA 21 in lipopolysaccharide-stimulated human dental pulp cells. J Cell Physiol. 2019 Nov;234(11):21331-21341.

7. Noda S, Kawashima N, Yamamoto M, Hashimoto K, Nara K, Sekiya I, Okiji T, Effect of cell culture density on dental pulp-derived mesenchymal stem cells with reference to osteogenic differentiation, SciRep, 9:5430, 2019.

8. Hirai K, Furusho H, Kawashima N, Xu S, de Beer MC, Battaglino R, Van Dyke T, Stashenko P, Sasaki H, Serum Amyloid A Contributes to Chronic Apical Periodontitis via TLR2 and TLR4, J Dent Res. 2019.

9. Bakhit A, Kawashima N, Hashimoto K, Noda S, Nara K, Kuramoto M, Tazawa K, and Okiji T, Strontium ranelate promotes odonto-/osteogenic differentiation/mineralization of dental papillae cells in vitro and mineralized tissue formation of the dental pulp in vivo, SciRep, 8:9224, 2018.

10. Tazawa K, Ikeda H, Kawashima N, Okiji T, Transient receptor potential melastatin (TRPM) 8 is expressed in freshly isolated native human odontoblasts, Arch Oral Biol. 2017.

11. Kawashima N, Noda S, Yamamoto M, Okiji T, Properties of dental pulp-derived mesenchymal stem cells and the effects of culture conditions, J Endod, 43(9S), S31-S34, 2017.

12. Suzuki N, Takimoto K, Kawashima N, Cathepsin K inhibitor regulates inflammation and bone destruction in experimentally-induced rat periapical lesions, J Endod, 41, 1474-9, 2015. 

Review Articles

1. Kawashima N and Okiji T, Odontoblasts: specialized hard-tissue-forming cells in the dentin-pulp complex, Congenit Anom (Kyoto), 56, 144-153, 2016. 

2. Kawashima N, Characterization of dental pulp stem cells: A new horizon for tissue regeneration?, Arch Oral Biol. 57, 1439-58, 2012.

Text Book

1. Kawashima N and Suda H, Pathological aspects of pulpal and periapical inflammations in : Orstavik D and Pitt Ford TR editors, Essential Endodontology, Oxford, Blackwell, 2008.

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