Kyushu University Academic Staff Educational and Research Activities Database
List of Papers
Naohisa Wada Last modified date:2020.01.09

Professor / Division of Interdisciplinary Dentistry / Comprehensive Dentistry / Kyushu University Hospital

1. Shoko Fujino, Sayuri Hamano, Atsushi Tomokiyo, Tomohiro Itoyama, Daigaku Hasegawa, Hideki Sugii, Shinichiro Yoshida, Ayako Washio, Aoi Nozu, Taiga Ono, Naohisa Wada, Chiaki Kitamura, Hidefumi Maeda, Expression and function of dopamine in odontoblasts, Journal of cellular physiology, 10.1002/jcp.29314, 2019.01, Dopamine (DA) is produced from tyrosine by tyrosine hydroxylase (TH). A recent study has reported that DA promotes the mineralization of murine preosteoblasts. However, the role of DA in odontoblasts has not been examined. Therefore, in this investigation, we researched the expression of TH and DA in odontoblasts and the effects of DA on the differentiation of preodontoblasts (KN-3 cells). Immunostaining showed that TH and DA were intensely expressed in odontoblasts and preodontoblasts of rat incisors and molars. KN-3 cells expressed D1-like and D2-like receptors for DA. Furthermore, DA promoted odontoblastic differentiation of KN-3 cells, whereas an antagonist of D1-like receptors and a PKA signaling blocker, inhibited such differentiation. However, antagonists of D2-like receptors promoted differentiation. These results suggested that DA in preodontoblasts and odontoblasts might promote odontoblastic differentiation through D1-like receptors, but not D2-like receptors, and PKA signaling in an autocrine or paracrine manner and plays roles in dentinogenesis..
2. Shinsuke Fujii, Kengo Nagata, Shinji Matsumoto, Kenichi Kouhashi, Akira Kikuchi, Yoshinao Oda, Tamotsu Kiyoshima, Naohisa Wada, Wnt/β-catenin signaling, which is activated in odontomas, reduces Sema3A expression to regulate odontogenic epithelial cell proliferation and tooth germ development, Scientific reports, 10.1038/s41598-019-39686-1, 9, 1, 2019.12, Odontomas, developmental anomalies of tooth germ, frequently occur in familial adenomatous polyposis patients with activated Wnt/β-catenin signaling. However, roles of Wnt/β-catenin signaling in odontomas or odontogenic cells are unclear. Herein, we investigated β-catenin expression in odontomas and functions of Wnt/β-catenin signaling in tooth germ development. β-catenin frequently accumulated in nucleus and/or cellular cytoplasm of odontogenic epithelial cells in human odontoma specimens, immunohistochemically. Wnt/β-catenin signaling inhibited odontogenic epithelial cell proliferation in both cell line and tooth germ development, while inducing immature epithelial bud formation. We identified Semaphorin 3A (Sema3A) as a downstream molecule of Wnt/β-catenin signaling and showed that Wnt/β-catenin signaling-dependent reduction of Sema3A expression resulted in suppressed odontogenic epithelial cell proliferation. Sema3A expression is required in appropriate epithelial budding morphogenesis. These results suggest that Wnt/β-catenin signaling negatively regulates odontogenic epithelial cell proliferation and tooth germ development through decreased-Sema3A expression, and aberrant activation of Wnt/β-catenin signaling may associate with odontoma formation..
3. Mai Arima, Daigaku Hasegawa, Shinichiro Yoshida, Hiromi Mitarai, Atsushi Tomokiyo, Sayuri Hamano, Hideki Sugii, Naohisa Wada, Hidefumi Maeda, R-spondin 2 promotes osteoblastic differentiation of immature human periodontal ligament cells through the Wnt/β-catenin signaling pathway, Journal of Periodontal Research, 10.1111/jre.12611, 54, 2, 143-153, 2019.04, Objective: In this study, we measured the expression of R-spondin 2 (RSPO2) in periodontal ligament (PDL) tissue and cells. Further, we examined the effects of RSPO2 on osteoblastic differentiation of immature human PDL cells (HPDLCs). Background: R-spondin (RSPO) family proteins are secreted glycoproteins that play important roles in embryonic development and tissue homeostasis through activation of the Wnt/β-catenin signaling pathway. RSPO2, a member of the RSPO family, has been reported to enhance osteogenesis in mice. However, little is known regarding the roles of RSPO2 in PDL tissues. Methods: Expression of RSPO2 in rat PDL tissue and primary HPDLCs was examined by immunohistochemical and immunofluorescence staining, as well as by semiquantitative RT-PCR. The effects of stretch loading on the expression of RSPO2 and Dickkopf-related protein 1 (DKK1) were assessed by quantitative RT-PCR. Expression of receptors for RSPOs, such as Leucine-rich repeat-containing G-protein-coupled receptors (LGRs) 4, 5, and 6 in immature human PDL cells (cell line 2-14, or 2-14 cells), was investigated by semiquantitative RT-PCR. Mineralized nodule formation in 2-14 cells treated with RSPO2 under osteoblastic inductive condition was examined by Alizarin Red S and von Kossa stainings. Nuclear translocation of β-catenin and expression of active β-catenin in 2-14 cells treated with RSPO2 were assessed by immunofluorescence staining and Western blotting analysis, respectively. In addition, the effect of Dickkopf-related protein 1 (DKK1), an inhibitor of Wnt/β-catenin signaling, was also examined. Results: Rat PDL tissue and HPDLCs expressed RSPO2, and HPDLCs also expressed RSPO2, while little was found in 2-14 cells. Expression of RSPO2 as well as DKK1 in HPDLCs was significantly upregulated by exposure to stretch loading. LGR4 was predominantly expressed in 2-14 cells, which expressed low levels of LGR5 and LGR6. RSPO2 enhanced the Alizarin Red S and von Kossa-positive reactions in 2-14 cells. In addition, DKK1 suppressed nuclear translocation of β-catenin, activation of β-catenin, and increases of Alizarin Red S and von Kossa-positive reactions in 2-14 cells, all of which were induced by RSPO2 treatment. Conclusion: RSPO2, which is expressed in PDL tissue and cells, might play an important role in regulating the osteoblastic differentiation of immature human PDL cells through the Wnt/β-catenin signaling pathway..
4. Yuriko Harada, Kenji Takeuchi, Michiko Furuta, Akihiko Tanaka, Shunichi Tanaka, Naohisa Wada, Yoshihisa Yamashita, Gender-dependent associations between occupational status and untreated caries in Japanese adults, Industrial health, 10.2486/indhealth.2018-0062, 56, 6, 539-544, 2018.11, The aim of this study was to examine whether the presence of untreated caries is different across occupational status among Japanese adults. This was a cross-sectional survey of 1,342 individuals (990 males and 352 females) aged 40-64 yr who underwent medical and dental checkups at a healthcare center in 2011. Oral examination was performed by a dentist and the presence of untreated caries was defined as having at least one untreated decayed tooth. Data regarding current occupational status were obtained using a self-administered questionnaire; the participants were classified into five groups: professionals and managers, clerical and related workers, service and salespersons, agricultural, forestry, and fishery workers, and homemakers and unemployed. Gender-specific odds ratios (ORs) and 95% confidence intervals (CIs) of occupational status for the presence of untreated caries were estimated using logistic regression. After adjusting for potential confounders, female professionals and managers (OR=3.51, 95% CI=1.04-11.87) and service and salespersons (OR=5.29, 95% CI=1.39-20.11) had greater risks of the presence of untreated caries than female homemakers and unemployed. However, this tendency was not observed among males. In conclusion, there was a significant difference in risk of the presence of untreated caries by occupational status among females..
5. Sayuri Hamano, Atsushi Tomokiyo, Daigaku Hasegawa, Shinichiro Yoshida, Hideki Sugii, Hiromi Mitarai, Shoko Fujino, Naohisa Wada, Hidefumi Maeda, Extracellular Matrix from Periodontal Ligament Cells Could Induce the Differentiation of Induced Pluripotent Stem Cells to Periodontal Ligament Stem Cell-Like Cells, Stem Cells and Development, 10.1089/scd.2017.0077, 27, 2, 100-111, 2018.01, The periodontal ligament (PDL) plays an important role in anchoring teeth in the bone socket. Damage to the PDL, such as after severe inflammation, can be treated with a therapeutic strategy that uses stem cells derived from PDL tissue (PDLSCs), a strategy that has received intense scrutiny over the past decade. However, there is an insufficient number of PDLSCs within the PDL for treating such damage. Therefore, we sought to induce the differentiation of induced pluripotent stem (iPS) cells into PDLSCs as an initial step toward PDL therapy. To this end, we first induced iPS cells into neural crest (NC)-like cells. We then captured the p75 neurotrophic receptor-positive cells (iPS-NC cells) and cultured them on an extracellular matrix (ECM) produced by human PDL cells (iPS-NC-PDL cells). These iPS-NC-PDL cells showed reduced expression of embryonic stem cell and NC cell markers as compared with iPS and iPS-NC cells, and enrichment of mesenchymal stem cell markers. The cells also had a higher proliferative capacity, multipotency, and elevated expression of PDL-related markers than iPS-NC cells cultured on fibronectin and laminin (iPS-NC-FL cells) or ECM produced by human skin fibroblast cells (iPS-NC-SF cells). Overall, we present a culture method to produce high number of PDLSC-like cells from iPS cells as a first step toward a strategy for PDL regeneration..
6. Aoi Nozu, Sayuri Hamano, Atsushi Tomokiyo, Daigaku Hasegawa, Hideki Sugii, Shinichiro Yoshida, Hiromi Mitarai, Shuntaro Taniguchi, Naohisa Wada, Hidefumi Maeda, Senescence and odontoblastic differentiation of dental pulp cells, Journal of cellular physiology, 10.1002/jcp.26905, 234, 1, 849-859, 2018.01, Cellular senescence has been suggested to be involved in physiological changes of cytokine production. Previous studies showed that the concentration of tumor necrosis factor-α (TNF-α) is higher in the blood of aged people compared with that of young people. So far, the precise effects of TNF-α on the odontoblastic differentiation of pulp cells have been controversial. Therefore, we aimed to clarify how this cytokine affected pulp cells during aging. Human dental pulp cells (HDPCs) were cultured until reaching the plateau of their growth, and the cells were isolated at actively (young HDPCs; yHDPCs) or inactively (senescent HDPCs; sHDPCs) proliferating stages. sHDPCs expressed senescence-related molecules while yHDPCs did not. When these HDPCs were cultured in an odontoblast-inductive medium, both young and senescent cells showed mineralization, but mineralization in sHDPCs was lower compared with yHDPCs. However, the administration of TNF-α to this culture medium altered these responses: yHDPCs showed downregulated mineralization, while sHDPCs exhibited significantly increased mineralization. Furthermore, the expression of tumor necrosis factor receptor 1 (TNFR1), a receptor of TNF-α, was significantly upregulated in sHDPCs compared with yHDPCs. Downregulation of TNFR1 expression led to decreased mineralization of TNF-α-treated sHDPCs, whereas restored the reduction in TNF-α-treated yHDPCs. These results suggested that sHDPCs preserved the odontoblastic differentiation capacity and TNF-α promoted odontoblastic differentiation of HDPCs with the progress of their population doublings through increased expression of TNFR1. Thus, TNF-α might exert a different effect on the odontoblastic differentiation of HDPCs depending on their proliferating activity. In addition, the calcification of pulp chamber with age may be related with increased reactivity of pulp cells to TNF-α..
7. 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..
8. 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..
9. H. Mizumachi, Shinichiro Yoshida, Atsushi Tomokiyo, Daigaku Hasegawa, Sayuri Hamano, Asuka Yuda, Hideki Sugii, Suguru Serita, Hiromi Mitarai, K. Koori, Naohisa Wada, Hidefumi Maeda, Calcium-sensing receptor-ERK signaling promotes odontoblastic differentiation of human dental pulp cells., Bone, 10.1016/j.bone.2017.05.012., 101, 191-201, 2017.02.
10. Suguru Serita, Atsushi Tomokiyo, Daigaku Hasegawa, Sayuri Hamano, Hideki Sugii, Shinichiro Yoshida, H. Mizumachi, Hiromi Mitarai, S. Monnouchi, Naohisa Wada, Hidefumi Maeda, Transforming growth factor-β-induced gene product-h3 inhibits odontoblastic differentiation of dental pulp cells., Arch Oral Biol, 10.1016/j.archoralbio.2017.02.018., 78, 135-143, 2017.02.
11. Shinichiro Yoshida, N. Yamamoto, Naohisa Wada, Atsushi Tomokiyo, Daigaku Hasegawa, Sayuri Hamano, H. Mitarai, S. Monnouchi, A. Yuda, Hidefumi Maeda, GDNF from Human Periodontal Ligament Cells Treated with Proinflammatory Cytokines Promotes Neurocytic Differentiation of PC12 Cells., J Cell Biochem, 10.1002/jcb.25662, 118, 4, 699-708, 2016.07.
12. 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..
13. Kana Hasegawa, Hiroko Wada, Kengo Nagata, Hiroaki Fujiwara, Naohisa Wada, Someya H, Mikami Y, Sakai Hidetaka, Tamotsu Kiyoshima, Facioscapulohumeral muscular dystrophy (FSHD) region gene 1 (FRG1) expression and possible function in mouse tooth germ development., J Mol Histol, 10.1007/s10735-016-9680-5, 47, 4, 375-387, 2016.05.
14. Monnouchi Satoshi, Hidefumi Maeda, Asuka Yuda, Suguru Serita, Naohisa Wada, Atsushi Tomokiyo, Akifumi Akamine, Benzo[a]pyrene/aryl hydrocarbon receptor signaling inhibits osteoblastic differentiation and collagen synthesis of human periodontal ligament cells., J Periodontal Res, in press, 2016.01.
15. 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.
16. 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.
17. Monnouchi Satoshi, Hidefumi Maeda, Asuka Yuda, Sayuri Hamano, Naohisa Wada, Atsushi Tomokiyo, Koori Katsuaki, Hideki Sugii, Suguru Serita, Akifumi Akamine, Mechanical induction of interleukin-11 regulates osteoblastic/cementoblastic differentiation of human periodontal ligament stem/progenitor cells., J Periodontal Res, in press, 2014.06.
18. Hideki Sugii, Hidefumi Maeda, Atsushi Tomokiyo, Naohide Yamamoto, Naohisa Wada, Koori Katsuaki, Daigaku Hasegawa, Sayuri Hamano, Asuka Yuda, Monnouchi Satoshi, Akifumi Akamine, Effects of Activin A on the phenotypic properties of human periodontal ligament cells., Bone, in press, 2014.06.
19. Asuka Yuda, Hidefumi Maeda, Fujii Shinsuke, Monnouchi Satoshi, Naohide Yamamoto, Naohisa Wada, Koori Katsuaki, Atsushi Tomokiyo, Sayuri Hamano, Daigaku Hasegawa, Akifumi Akamine, Effect of CTGF/CCN2 on osteo/cementoblastic and fibroblastic differentiation of a human periodontal ligament stem/progenitor cell line., J Cell Physiol, Epub ahead of print, 2014.06.
20. Yoko Teramatsu, Hidefumi Maeda, Hideki Sugii, Atsushi Tomokiyo, Sayuri Hamano, Naohisa Wada, Asuka Yuda, Naohide Yamamoto, Katsuaki Koori, Akifumi Akamine, Expression and effects of epidermal growth factor on human periodontal ligament cells., Cell Tissue Res, 2014.05.
21. Koori Katsuaki, Hidefumi Maeda, Fujii Shinsuke, Atsushi Tomokiyo, G Kawachi, Daigaku Hasegawa, Sayuri Hamano, Hideki Sugii, Naohisa Wada, Akifumi Akamine, The roles of calcium-sensing receptor and calcium channel in osteogenic differentiation of undifferentiated periodontal ligament cells., Cell Tissue Res, Epub ahead of print, 2014.05.
22. 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.
23. 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.
24. 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.
25. Kono Kiyomi, Hidefumi Maeda, Fujii Shinsuke, Atsushi Tomokiyo, Yamamoto N, Naohisa Wada, Monnouchi Satoshi, Teramatsu Y, Hamano S, Koori K, Akifumi Akamine, Exposure to transforming growth factor-β1 after basic fibroblast growth factor promotes the fibroblastic differentiation of human periodontal ligament stem/progenitor cell lines., Cell Tissue Res, 352, 2, 249-263, 2013.05.
26. Teramachi J, Kukita A, Qu P, naohisa wada, Li YJ, Toshio Kukita, Adenosine blocks aminopterin-induced suppression of osteoclast differentiation., J Bone Miner Metab, 31, 1, 64-70, 2013.01.
27. Atsushi Tomokiyo, Hidefumi Maeda, Fujii Shinsuke, Monnouchi Satoshi, naohisa wada, Kono Kiyomi, Koori K, Yamamoto N, Teramatsu Y, Akifumi Akamine, Alternation of extracellular matrix remodeling and apoptosis by activation of the aryl hydrocarbon receptor pathway in human periodontal ligament cells., J Cell Biochem, 113, 10, 3093-3103, 2012.05.
28. Yamamoto N, Maeda H, Tomokiyo A, Fujii S, Wada N, Monnouchi S, Kono K, Koori K, Teramatsu Y, Akamine A, Expression and effects of glial cell line-derived neurotrophic factor on periodontal ligament cells., J Clin Periodontol, 39, 6, 556-564, 2012.06.
29. naohisa wada, Hidefumi Maeda, Kono Kiyomi, Atsushi Tomokiyo, Monnouchi Satoshi, Katsuaki Koori, Naohide Yamamoto, Yoko Teramatsu, Akifumi Akamine, A multipotent clonal human periodontal ligament cell line with neural crest cell phenotypes promotes neurocytic differentiation, migration, and survival., J Cell Physiol, 227, 5, 2040-2050, 2012.05.
30. Maeda H, Tomokiyo A, Koori K, Monnouchi S, Fujii S, Wada N, Kono K, Yamamoto N, Saito T, Akamine A, An in vitro evaluation of two resin-based sealers on proliferation and differentiation of human periodontal ligament cells., Int Endod J, 44, 5, 425-431, 2011.07.
31. 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.
32. Teramachi J, Kukita A, Li YJ, Ushijima Y, Ohkuma H, Wada N, Watanabe T, Nakamura S, Kukita T, Adenosine abolishes MTX-induced suppression of osteoclastogenesis and inflammatory bone destruction in adjuvant-induced arthritis, Lab Invest, 91, 5, 719-731, 2011.05.
33. 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.
34. Fujii S, Maeda H, Tomokiyo A, Monnouchi S, Hori K, Wada N, Akamine A, Effects of TGF-β1 on the proliferation and differentiation of human periodontal ligament cells and a human periodontal ligament stem/progenitor cell line, Cell Tissue Res, 2010.10.
35. Maeda H, Nakano T, Tomokiyo A, Fujii S, Wada N, Monnouchi S, Hori K, Akamine A, Mineral trioxide aggregate induces bone morphogenetic protein-2 expression and calcification in human periodontal ligament cells, J Endod, 36, 4, 647-652, 2010.04.
36. 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.
37. 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.
38. 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.
39. SEM images of root canal dentin irrigated with EDTA and NaOCl -Comparison with ultrasonic irrigation-.
40. Effects of root-end filling materials on the osteoblast-like differentiation of human periodontal ligament cells.
41. 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.
42. 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.
43. Watanabe T, Kukita T, Kukita A, Wada N, Toh K, Nagata K, Nomiyama H, Iijima T, Direct stimulation of osteoclastogenesis by MIP-1: evidence obtained from studies using RAW 264 cell clone highly responsive to RANKL., Journal of Endocrinology, 10.1677/joe.0.1800193, 180, 1, 193-201, vol.180: pp193-201, 2004.01.
44. 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.
45. 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.
46. Maeda H, Wada N, Fujii S, Akamine A, Fibroblastic cells from human periapical granulation tissue preferentially form calcified matrices in decalcified and boiled rat bone., Cell and Tissue Research, 10.1007/s00441-004-1052-x, 320, 1, 135-140, vol.320: pp135-140, 2005.01.
47. Maeda H, Wada N, Nakamuta H, Akamine A, Human periapical granulation tissue contains osteogenic cells., Cell and Tissue Research, 10.1007/s00441-003-0832-z, 315, 2, 203-208, vol.35: pp203-208, 2004.01.
48. Hashiguchi I, Yoshimine Y, Gotou Y, Maeda H, Wada N, Akamine A, Fukuyama H, Okumura H, An epidemiologic examination on the prevalence of the periodontal diseases and oral pigmentation in yusho patients in 2002. . 94: 81-86, 2003., Fukuoka Acta Medica, vol.94: pp81-86, 2003.01.
49. 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.
50. Maeda H, Hashiguchi I, Nakamuta H, Toriya Y, Wada N, Akamine A, Histological study of periapical tissue healing in the Rat Molar after retrofilling with various materials., Journal of Endodontics, 10.1016/S0099-2399(99)80397-5, 25, 1, 38-42, vol.25: pp38-42, 1999.01.