Kyushu University Academic Staff Educational and Research Activities Database
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Naohisa Wada Last modified date:2018.06.25

Professor / Division of Interdisciplinary Dentistry
Comprehensive Dentistry
Kyushu University Hospital


Graduate School
Undergraduate School
Other Organization


E-Mail
Homepage
http://www.dent.kyushu-u.ac.jp/dh/
Kyushu University Hospital Dental Center .
Phone
092-642-6490
Academic Degree
Ph.D
Country of degree conferring institution (Overseas)
No
Field of Specialization
General Dentistry (Endodontology, Operative Dentistry, Periodontology)
Total Priod of education and research career in the foreign country
00years00months
Outline Activities
research: To achieve regeneration of periodontal ligament, I study about chracterization of periodontal ligament and searching the specific factor for periodontal ligament.
Research
Research Interests
  • Establishing novel method to regenerate dentin-dental pulp complex using stem cells, signal molecules and scaffolds.
    keyword : dental pulp, dentin, stem cell, tissure engineering
    2013.04.
  • Identification of novel growth factor and extracellular matrix protein which are specific in periodontal ligament stem cell population
    keyword : Periodontal ligament stem cell
    2010.04.
  • Reprogramming of human gingival fibroblasts and periodontal ligament cells to pluripotency with defined factors
    keyword : gingival cell, periodontal ligament cell, iPS
    2008.04~2009.03.
  • Immunosuppressive mechanisms of allogeneic periodontal ligament stem cells on T-lymphocytes
    keyword : periodontal ligament stem cell, T-lymophocyte, allogeneic transplantation
    2007.09~2010.03.
  • Identification of novel factors to induce periodontal tissue regeneration
    keyword : periodontal ligament
    2006.04.
  • Establishment and characterisation of human periodontal ligament cell clone and epithelial cell clone derived from human epithelial rests of Malassez
    keyword : periodontal ligament, cell clone
    2003.04~2006.03.
  • Lipopolysaccharide stimulates expression of osteoprotegerin and receptor activator of NF-kappa B ligand in periodontal ligament fibroblasts through the induction of interleukin-1 beta and tumor necrosis factor-alpha
    keyword : periodontal ligament, osteoclast, LPS
    2001.04~2003.03.
  • The study of the mechanism(s) and the factor for periodontal ligament cells to regulate the osteoclast differentiation and function
    keyword : periodontal ligament, osteoclast
    1998.04~2002.03.
  • Apoptosis of epithelial cells proliferated in human periapical lesions
    keyword : periapical granuloma, periapical cyst, apoptosis
    1997.04~1998.03.
Academic Activities
Books
1. Naohisa Wada, Atsushi Tomokiyo, Hidefumi Maeda, Dental Stem Cells, Springer International Publishing Switzerland, 2016.05.
2. Hidefumi Maeda, Naohisa Wada, Fujii Shinsuke, Atsushi Tomokiyo, Akifumi Akamine, Periodontal ligament stem cells. In: Stem Cells in Clinic and Research, InTech, Rijeka, Croatia, Chapter 25, 619-636, 2011.07.
Reports
1. Naohisa wada, Stan Gronthos, P.Mark Bartold, Immunomodulatory Effects of Stem Cells, Periodontol 2000. 63(1):198-216., 63(1):198-216, 2013.10.
Papers
1. H. Mitarai, Naohisa Wada, Daigaku Hasegawa, Shinichiro Yoshida, M. Sonoda, Atsushi Tomokiyo, Sayuri Hamano, S. Serita, H. Mizumachi, Hidefumi Maeda, Transgelin mediates transforming growth factor-β1-induced proliferation of human periodontal ligament cells, Journal of Periodontal Research, 10.1111/jre.12466, 52, 6, 984-993, 2017.12, Background and Objective: Human periodontal ligament cells (HPDLCs) express transforming growth factor-β1 (TGF-β1) that regulates differentiation and proliferation, and plays key roles in homeostasis of PDL tissue. Transgelin is a cytoskeleton-associated protein with an Smad-binding element in its gene promoter region. In this study, we examined the localization and potential function of transgelin in PDL tissue and cells. Material and Methods: Microarray analysis of HPDLC lines (2-14, 2-23 and 2-52) was performed. Expression of transgelin in HPDLCs was examined by quantitative reverse transcription–polymerase chain reaction, immunofluorescence staining and western blot analysis. Effects of TGF-β1 and its signaling inhibitor, SB431542, on transgelin expression in HPDLCs were examined by western blot analysis. The effects of transgelin knockdown by small interfering RNA (siRNA) on HPDLC proliferation stimulated by TGF-β1 were assessed by WST-1 assay. Results: In microarray and quantitative reverse transcription–polymerase chain reaction analyses, the expression levels of transgelin (TAGLN) in 2-14 and 2-23 cells, which highly expressed PDL markers such as periostin (POSTN), tissue non-specific alkaline phosphatase (ALPL), α-smooth muscle actin (ACTA2) and type I collagen A1 (COL1A1), was significantly higher than those in 2-52 cells that expressed PDL markers weakly. Immunohistochemical and immunofluorescence staining revealed expression of transgelin in rat PDL tissue and HPDLCs. In HPDLCs, TGF-β1 treatment upregulated transgelin expression, whereas inhibition of the type 1 TGF-β1 receptor by SB431542 suppressed this upregulation. Furthermore, TAGLN siRNA transfection did not promote the proliferation of HPDLCs treated with TGF-β1. The expression levels of CCNA2 and CCNE1, which regulate DNA synthesis and mitosis through the cell cycle, were also not upregulated in HPDLCs transfected with TAGLN siRNA. Conclusion: Transgelin is expressed in PDL tissue and might have a role in HPDLC proliferation induced by TGF-β1 stimulation..
2. Daigaku Hasegawa, Naohisa Wada, Shinichiro Yoshida, Hiromi Mitarai, Mai Arima, Atsushi Tomokiyo, Sayuri Hamano, Hideki Sugii, Hidefumi Maeda, Wnt5a suppresses osteoblastic differentiation of human periodontal ligament stem cell-like cells via Ror2/JNK signaling, Journal of Cellular Physiology, 10.1002/jcp.26086, 233, 2, 1752-1762, 2018.02, Wnt5a, a non-canonical Wnt protein, is known to play important roles in several cell functions. However, little is known about the effects of Wnt5a on osteoblastic differentiation of periodontal ligament (PDL) cells. Here, we examined the effects of Wnt5a on osteoblastic differentiation and associated intracellular signaling in human PDL stem/progenitor cells (HPDLSCs). We found that Wnt5a suppressed expression of bone-related genes (ALP, BSP, and Osterix) and alizarin red-positive mineralized nodule formation in HPDLSCs under osteogenic conditions. Immunohistochemical analysis revealed that a Wnt5a-related receptor, receptor tyrosine kinase-like orphan receptor 2 (Ror2), was expressed in rat PDL tissue. Interestingly, knockdown of Ror2 by siRNA inhibited the Wnt5a-induced downregulation of bone-related gene expression in HPDLSCs. Moreover, Western blotting analysis showed that phosphorylation of the intracellular signaling molecule, c-Jun N-terminal kinase (JNK) was upregulated in HPDLSCs cultured in osteoblast induction medium with Wnt5a, but knockdown of Ror2 by siRNA downregulated the phosphorylation of JNK. We also examined the effects of JNK inhibition on Wnt5a-induced suppression of osteoblastic differentiation of HPDLSCs. The JNK inhibitor, SP600125 inhibited the Wnt5a-induced downregulation of bone-related gene expression in HPDLSCs. Additionally, SP600125 inhibited the Wnt5a-induced suppression of the alizarin red-positive reaction in HPDLSCs. These results suggest that Wnt5a suppressed osteoblastic differentiation of HPDLSCs through Ror2/JNK signaling. Non-canonical Wnt signaling, including Wnt5a/Ror2/JNK signaling, may function as a negative regulator of mineralization, preventing the development of non-physiological mineralization in PDL tissue..
3. Shinichiro Yoshida, Naohisa Wada, Daigaku Hasegawa, H. Miyaji, H. Mitarai, Atsushi Tomokiyo, Sayuri Hamano, Hidefumi Maeda, Semaphorin 3A Induces Odontoblastic Phenotype in Dental Pulp Stem Cells., J Dent Res, 10.1177/0022034516653085, 95, 11, 1282-1290, 2016.06, In cases of pulp exposure due to deep dental caries or severe traumatic injuries, existing pulp capping materials have a limited ability to reconstruct dentin/pulp complexes and can result in pulpectomy because of their low potentials to accelerate dental pulp cell activities such as migration, proliferation, and differentiation. Therefore, the development of more effective therapeutic agents has been anticipated for direct pulp capping. It is known that dental pulp tissues are enriched with dental pulp stem cells (DPSCs). Here, we investigated the effects of semaphorin 3A (Sema3A) on various functions of human DPSCs in vitro and reparative dentin formation in a rat dental pulp exposure model in vivo. Immunofluorescence staining revealed expression of Sema3A and its receptor, neuropilin 1 (Nrp1), in rat dental pulp tissue and human DPSC clones. Sema3A induced cell migration, chemotaxis, proliferation, and odontoblastic differentiation of DPSC clones. In addition, Sema3A treatment of DPSC clones increased β-catenin nuclear accumulation, upregulated expression of the FARP2 (FERM, RhoGEF, and pleckstrin domain protein 2) gene, and activated Rac1 in DPSC clones. Furthermore, in the rat dental pulp exposure model, Sema3A promoted reparative dentin formation with dentin tubules and a well-aligned odontoblast-like cell layer at the dental pulp exposure site, and novel reparative dentin almost completely covering pulp tissue at 4 weeks after direct pulp capping. These findings suggest that Sema3A could play an important role in dentin regeneration via canonical Wnt/β-catenin signaling. Sema3A might be an alternative agent for direct pulp capping, which requires further study..
4. Daigaku Hasegawa, Naohisa Wada, Hidefumi Maeda, S.Yoshida, H. Mitarai, Atsushi Tomokiyo, Monnouchi Satoshi, S. Hamano, A. Yuda, Akifumi Akamine, Wnt5a Induces Collagen Production by Human Periodontal Ligament Cells through TGFβ1-mediated Upregulation of Periostin Expression., J Cell Physiol, 230, 11, 2647-2660, 2015.11.
5. Zakaria MN, Toru Takeshita, Yukie Shibata, Hidefumi Maeda, Naohisa Wada, Akifumi Akamine, Yoshihisa Yamashita, Microbial community in persistent apical periodontitis: a 16S rRNA gene clone library analysis., Int Endod J, in press, 2014.08.
6. Naohisa Wada, Hidefumi Maeda, Hasegawa D, Gronthos S, Bartold PM, Menicanin D, Fujii S, Yoshida D, Tomokiyo A, Monnouchi Satoshi, Akifumi Akamine, Semaphorin 3A induces mesenchymal stem-like properties in human periodontal ligament cells., Stem Cells Dev, in press, 2014.02.
7. Menicanin D, Mrozik M, Naohisa Wada, Marino V, Shi S, Bartold PM, Gronthos S., Periodontal Ligament Derived Stem Cells Exhibit the Capacity for Long-Term Survival, Self-Renewal and Regeneration of Multiple Tissue Types in Vivo. , Stem Cells Dev, 23, 9, 1001-1011, 2014.05.
8. Mrozik K, Naohisa Wada, Marino V, Richter W, Shi S, Wheeler DL, Gronthos S, Bartold PM, Regeneration of periodontal tissues using allogeneic periodontal ligament stem cells in an ovine model., Regen Med, 8, 6, 711-723, 2013.06.
9. Wada N, Wang B, Lin NH, Laslett AL, Gronthos S, Bartold PM, Induced pluripotent stem cell lines derived from human gingival fibroblasts and periodontal ligament fibroblasts., J Periodontal Res, 46, 4, 438-447, 2011.05.
10. Wada N, Bartold PM, Gronthos S, Human foreskin fibroblasts exert immunomodulatory properties by a different mechanism to bone marrow mesenchymal stem cells, Stem Cells Dev, 20, 4, 647-659, 2010.09.
11. Wada N, Menicanin D, Shi S, Bartold PM, Gronthos S, Immunomodulatory properties of human periodontal ligament stem cells, J Cell Physiol, 219, 667-676, 2009.01.
12. Fujii S, Maeda H, Wada N, Tomokiyo A, Saito M, Akamine A., Investigating a clonal human periodontal ligament progenitor/stem cell line in vitro and in vivo, J Cell Physiol, 215, 3, 743-749, 2008.03.
13. Tomokiyo A, Maeda H, Fujii S, Wada N, Shima K, Akamine A, Development of a multipotent clonal human periodontal ligament cell line. Differentiation, Differentiation, 76, 4, 337-347, 2008.04.
14. Fujii S, Maeda H, Wada N, Kano Y, Akamine A, Establishing and characterizing human periodontal ligament fibroblasts immortalized by SV40T-antigen and hTERT gene transfer., Cell and Tissue Research, vol.324(1):pp117-125, 2006.04.
15. Nomiyama H, Egami K, Wada N, Tou K, Horiuchi M, Matsusaki H, Miura R, Yoshie O, Kukita T, Identification of genes differentially expressed in osteoclast-like cells., Journal of Interferon and Cytokine Research, 10.1089/jir.2005.25.227, 25, 4, 227-231, vol.25: pp227-231, 2005.01.
16. Wada N, Maeda H, Yoshimine Y, Akamine A, Lipopolysaccharide stimulates expression of osteoprotegerin and receptor activator of NF-kappa B ligand in periodontal ligament fibroblasts through the induction of interleukin-1 beta and tumor necrosis factor-alpha., Bone, 10.1016/j.bone.2004.04.023, 35, 3, 629-635, vol.35: pp629-635, 2004.04.
17. Kukita T, Wada N, Kukita A, Kakimoto T, Sandra F, Toh K, Nagata K, Iijima T, Horiuchi M, Matsusaki H, Hieshima K, Yoshie O, Nomiyama H., RANKL-induced DC-STAMP is essential for osteoclastogenesis., Journal of Experimental Medicine, 10.1084/jem.20040518, 200, 7, 941-946, vol.200: pp941-946, 2004.06.
18. Wada N, Maeda H, Tanabe K, Tsuda E, Yano K, Nakamuta H, Akamine A, Periodontal ligament cells secrete the factor that inhibits osteoclastic differentiation and function: the factor is osteoprotegerin / osteoclastogenesis inhibitory factor., Journal of Periodontal Research, 10.1034/j.1600-0765.2001.00604.x, 36, 1, 56-63, vol.36: pp56-63, 2001.01.
Presentations
1. Hiromi Mitarai, Naohisa Wada, Daigaku Hasegawa, Shinichiro Yoshida, Mai Sonoda, Atsushi Tomokiyo, Sayuri Hamano, Hidefumi Maeda, Transgelin Mediates TGF-beta1-induced Human Periodontal Ligament Cell Proliferation., 95th General Session & Exhibition of the International Association for Dental Research (IADR), 2017.03.
2. Daigaku Hasegawa, Naohisa Wada, Sayuri Hamano, Atsushi Tomokiyo, Shinichiro Yoshida, Hiromi Mitarai, Mai Sonoda, Hideki Sugii, Hidefumi Maeda, Identification of a novel periodontal ligament stem cell marker, 94th General Session & Exhibition of the International Association for Dental Research (IADR), 2016.06.
3. Shinichiro Yoshida, Naohisa Wada, Daigaku Hasegawa, Atsushi Tomokiyo, Sayuri Hamano, Hiromi Mitarai, Hideki Sugii, Hidefumi Maeda, Semaphorin 3A induces odontoblastic phenotype in dental pulp stem cells., 94th General Session & Exhibition of the International Association for Dental Research (IADR), 2016.06.
4. Sayuri Hamano, Atsushi Tomokiyo, Naohisa Wada, Daigaku Hasegawa, Hideki Sugii, Shinichiro Yoshida, Suguru Serita, Hiroyuki Mizumachi, Hiromi Mitarai, Hidefumi Maeda, Directing human iPS cells toward PDL stem cells, 94th General Session & Exhibition of the International Association for Dental Research (IADR), 2016.06.
5. Shinichiro Yoshida, Naohisa Wada, Daigaku Hasegawa, Atsushi Tomokiyo, Sayuri Hamano, Hiromi Mitarai, Serita S, Mizumachi H, Hidefumi Maeda, Semaphorin 3A induces odontoblastic phenotype in dental pulp stem cells., Kyudai Oral Bioscience 2016 -Frontiers in Dental Research and Education in East Asia-, 2016.02.
6. Daigaku Hasegawa, Naohisa Wada, Hidefumi Maeda, Shinichiro Yoshida, Monnouchi Satoshi, Koori Katsuaki, Sayuri Hamano, Hiromi Mitarai, Akifumi Akamine, The Effects of Wnt5a on Human Periodontal Ligament Cells., Kyudai Oral Bioscience 2014 - 8th International Symposium -, 2014.02.
7. Shinichiro Yoshida, naohisa wada, Hidefumi Maeda, Daigaku Hasegawa, Sato H, Monnouchi Satoshi, Akifumi Akamine, Dental pulp stem cells on bone tissue express periodontal ligament-related gene., The 9th World Endodontic Congress, 2013.05.
8. naohisa wada, Hidefumi Maeda, Daigaku Hasegawa, Stan Gronthos, P.Mark Bartold, Daniela Menicanin, Fujii Shinsuke, Hiroko Wada, Atsushi Tomokiyo, Monnouchi Satoshi, Akifumi Akamine, Conversion of periodontal ligament cells into multipotent stem-like cells, 91st General Session & Exhibition of the IADR, 2013.03.
9. naohisa wada, Hidefumi Maeda, Daigaku Hasegawa, Stan Gronthos, P.Mark Bartold, Daniela Menicanin, Fujii Shinsuke, Hiroko Wada, Atsushi Tomokiyo, Monnouchi Satoshi, Akifumi Akamine, Induction of stem/undifferentiated cells from human periodontal ligament cells by Sema3A, The Australian Health and Medical Research Congress 2012, 2012.11.
10. Immunosuppressive properties of human periodontal ligament stem cells.
Membership in Academic Society
  • Pierre Fauchard Academy
  • Japanese society of regenerative medicine
Educational
Educational Activities
My educational activities are supervision and direction of Residents and students of 5th and 6th grade. Especially, general dental treatments, operative dentistry and endodontology are my specialty to teach young doctors.
Other Educational Activities
  • 2018.05.
  • 2017.12.
  • 2017.11.
  • 2016.03.
  • 2015.12.
  • 2015.09.
  • 2015.09.
  • 2015.07.
  • 2015.03.
  • 2014.05.
  • 2011.11.
  • 2010.04.
  • 2010.08.
  • 2010.09.
  • 2007.05.
  • 2006.09.
  • 2006.06.
  • 2006.06.
  • 2005.10.