Kyushu University Academic Staff Educational and Research Activities Database
List of Papers
Kyumoto Yukari Last modified date:2020.06.01

Assistant Professor / Oral Biological Science / Department of Dental Science / Faculty of Dental Science

1. Yosuke Tanaka, Soichiro Sonoda, Haruyoshi Yamaza, Sara Murata, Kento Nishida, Shion Hama, Yukari Kyumoto-Nakamura, Norihisa Uehara, Kazuaki Nonaka, Toshio Kukita, Takayoshi Yamaza, Suppression of AKT-mTOR signal pathway enhances osteogenic/dentinogenic capacity of stem cells from apical papilla, Stem Cell Research and Therapy, 10.1186/s13287-018-1077-9, 9, 1, 2018.11, Background: Stem cells from apical papilla (SCAP) are a subpopulation of mesenchymal stem cells (MSCs) isolated from the apical papilla of the developing tooth root apex of human teeth. Because of their osteogenic/dentinogenic capacity, SCAP are considered as a source for bone and dentin regeneration. However, little is understood about the molecular mechanism of osteogenic/dentinogenic differentiation of SCAP. Phosphoinositide 3 kinase (PI3K)-AKT-mammalian target of rapamycin (mTOR) signal pathway participates in regulating the differentiation of various cell types, such as MSCs. In this study, we examined the role of the PI3K-AKT-mTOR signal pathway in the osteogenic/dentinogenic differentiation of SCAP. Moreover, we challenge to fabricate scaffold-free SCAP-based spheroidal calcified constructs. Methods: SCAP were pretreated with or without small interfering RNA for AKT (AKT siRNA), PI3K inhibitor LY294402, and mTOR inhibitor rapamycin and were cultured under osteogenic/dentinogenic differentiation to examine in vitro and in vivo calcified tissue formation. Moreover, SCAP-based cell aggregates were pretreated with or without LY294402 and rapamycin. The cell aggregates were cultured under osteogenic/dentinogenic condition and were analyzed the calcification of the aggregates. Results: Pretreatment with AKT siRNA, LY294402, and rapamycin enhances the in vitro and in vivo calcified tissue-forming capacity of SCAP. SCAP were fabricated as scaffold-free spheroids and were induced into forming calcified 3D constructs. The calcified density of the spheroidal constructs was enhanced when the spheroids were pretreated with LY294402 and rapamycin. Conclusions: Our findings indicate that the suppression of PI3K-AKT-mTOR signal pathway plays a role in not only enhancing the in vivo and in vitro osteogenic/dentinogenic differentiation of SCAP, but also promoting the calcification of scaffold-free SCAP-based calcified constructs. These findings suggest that a suppressive regulation of PI3K-AKT-mTOR signal pathway is a novel approach for SCAP-based bone and dentin regeneration..
2. Tamer Badawy, Yukari Kyumoto-Nakamura, Norihisa Uehara, Jingqi Zhang, Soichiro Sonoda, Hidenobu Hiura, Takayoshi Yamaza, Akiko Kukita, Toshio Kukita, Osteoblast lineage-specific cell-surface antigen (A7) regulates osteoclast recruitment and calcification during bone remodeling, Laboratory Investigation, 10.1038/s41374-018-0179-4, 2019.01, Bone remodeling is a continuous process characterized by highly coordinated cell-cell interactions in distinct multi-cellular units. Osteoclasts, which are specialized bone resorbing cells, play a central role in bone remodeling. Although the RANKL/RANK axis determines the gross number of osteoclasts present in bone tissue, detailed molecular events regulating bone remodeling related to osteoclast recruitment, initiation of bone remodeling, and coupling of bone resorption and bone formation are still ambiguous. We hypothesized that osteoblast-specific cell-surface molecules contribute to the molecular modulation of bone remodeling. Therefore, we searched for regulatory cell-surface molecules expressed on osteoblasts by use of B-cell hybridoma technology. We obtained a monoclonal antibody A7 (A7 MAb) highly specific to cells of osteoblast-lineage. Here we describe the expression pattern and possible role of A7 antigen specifically recognized by A7 MAb. In vitro, A7 antigen was expressed on cell-surface of osteoblasts and osteoblast-like bone marrow stromal cells. In vivo, A7 antigen was detected in a subset of bone surface osteoblasts and in osteocytes, with a typical cell membrane expression pattern. Tissue array analysis showed only a limited expression of A7 antigen in osteocytes close to the bone surface. Immunoblotting and immunoprecipitation analysis showed that A7 antigen is a lineage-specific cell-surface protein with an approximate molecular weight of 45 KDa. Cross-linking of cell-surface A7 antigen in cultures of osteoclastogenesis showed stimulation of osteoclast formation. Marked suppression of calcification in primary osteoblast cultures was observed when A7 antigen was cross-linked with anti-A7 antigen MAb, A7 MAb. These data suggest that A7 antigen regulates recruitment of osteoclasts and triggering of calcification. A7 antigen may be an important molecule involved in the precise regulation of bone remodeling..
3. Yosuke Tanaka, Soichiro Sonoda, Haruyoshi Yamaza, Sara Murata, Kento Nishida, Yukari Kyumoto-Nakamura, Norihisa Uehara, Kazuaki Nonaka, Toshio Kukita, Takayoshi Yamaza, Acetylsalicylic Acid Treatment and Suppressive Regulation of AKT Accelerate Odontogenic Differentiation of Stem Cells from the Apical Papilla, Journal of Endodontics, 10.1016/j.joen.2019.01.016, 45, 5, 591-598.e6, 2019.05, Introduction: Stem cells isolated from the root apical papilla of human teeth (stem cells from the apical papilla [SCAPs])are capable of forming tooth root dentin and are a feasible source for bioengineered tooth root regeneration. In this study, we examined the effect of acetylsalicylic acid (ASA)on odontogenic differentiation of SCAPs in vitro and in vivo. Methods: SCAPs were cultured under odontogenic conditions supplemented with or without ASA. ASA-treated SCAPs were also subcutaneously transplanted into immunocompromised mice. Results: ASA accelerates in vitro and in vivo odontogenic differentiation of SCAPs associated with down-regulation of runt-related nuclear factor 2 and up-regulation of specificity protein 7, nuclear factor I C, and dentin phosphoprotein. ASA up-regulated the phosphorylation of AKT in the odontogenic SCAPs. Of interest, pretreatments with phosphoinositide 3-kinase inhibitor LY294402 and small interfering RNA for AKT promoted ASA-induced in vitro and in vivo odontogenic differentiation of SCAPs. LY294402 and small interfering RNA for AKT also suppressed the ASA-induced expression of runt-related nuclear factor 2 and enhanced ASA-induced expression of specificity protein 7, nuclear factor I C, and dentin phosphoprotein in SCAPs. Conclusions: These findings suggest that a combination of ASA treatment and suppressive regulation of the phosphoinositide 3-kinase–AKT signaling pathway is a novel approach for SCAP-based tooth root regeneration..
4. Sonoda S., Mei Y. F., Atsuta I., Danjo A., Yamaza H., Hama S., Nishida K., Tang R., Kyumoto-Nakamura Y., Uehara N., Kukita T., Nishimura F., Yamaza T., Exogenous nitric oxide stimulates the odontogenic differentiation of rat dental pulp stem cells, SCIENTIFIC REPORTS, 10.1038/s41598-018-21183-6, 8, 2018.02.
5. Takuma Shiratori, Yukari Kyumoto-Nakamura, Akiko Kukita, Norihisa Uehara, Jingqi Zhang, Kinuko Koda, Mako Kamiya, Tamer Badawy, Erika Tomoda, Xianghe Xu, Takayoshi Yamaza, Yasuteru Urano, Kiyoshi Koyano and Toshio Kukita, IL-1β Induces Pathologically Activated Osteoclasts Bearing Extremely High Levels of Resorbing Activity: A Possible Pathological Subpopulation of Osteoclasts, Accompanied by Suppressed Expression of Kindlin-3 and Talin-1, The Journal of Immunology, 2018.01.
6. Uehara N., Kukita A., Kyumoto-Nakamura Y., Yamaza T., Yasuda H., Kukita T. , Osteoblast-derived Laminin-332 is a novel negative regulator of osteoclastogenesis in bone microenvironments, LABORATORY INVESTIGATION, 10.1038/labinvest.2017.55, 97, 10, 1235-1244, 2017.10.
7. Hinoi E., Nakamura Y., Takada S., Fujita H., Iezaki T., Hashizume S., Takahashi S., Odaka Y., Watanabe T., Yoneda Y., Growth differentiation factor-5 promotes brown adipogenesis in systemic energy expenditure., Diabetes, 63, 1, 162-175, 2014.01, Although growth differentiation factor-5 (GDF5) has been implicated in skeletal development and joint morphogenesis in mammals, little is known about its functionality in adipogenesis and energy homeostasis. Here, we show a critical role of GDF5 in regulating brown adipogenesis for systemic energy expenditure in mice. GDF5 expression was preferentially upregulated in brown adipose tissues from inborn and acquired obesity mice. Transgenic overexpression of GDF5 in adipose tissues led to a lean phenotype and reduced susceptibility to diet-induced obesity through increased systemic energy expenditure. Overexpression of GDF5 facilitated the development of brown fat-like cells, called brite or beige cells, along with the expression of uncoupling protein-1 in inguinal subcutaneous white adipose tissue. In mutant mice harboring the dominant-negative GDF5, marked impairment in energy expenditure and thermogenesis was seen under obesogenic conditions. Recombinant GDF5 promoted brown adipogenesis through the mothers against decapentaplegic homolog (Smad) and peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α) pathways after activation of bone morphogenetic protein receptor (BMPR). These results suggest that brown adipogenesis and energy homeostasis are both positively regulated by the GDF5/BMPR/Smad/PGC-1α signaling pathway in adipose tissues. Modulation of these pathways might be an effective therapeutic strategy for obesity and type 2 diabetes..
8. Nakamura Y.*, Hinoi E.*, Iezaki T., Takada S., Hashizume S., Takahata Y., Tsuruta E., Takahashi S., Yoneda Y. , Repression of adipogenesis through promotion of Wnt/ß-catenin signaling by TIS7 up-regulated in adipocytes under hypoxia. , BBA Mol. Basis Dis., 1832, 1117-1128, 2013.08.
9. Takahata Y., Hinoi E., Takarada T., Nakamura Y., Ogawa S., Yoneda Y., Positive regulation by GABA(B) receptor subunit-1 of chondrogenesis through acceleration of nuclear translocation of activating transcription factor-4., J. Biol. Chem., 287, 33293-33303, 2012.09.
10. Takarada T., Takarada-Iemata M., Takahata Y., Yamada D., Yamamoto T., Nakamura Y., Hinoi E., Yoneda Y. , Osteoclastogenesis is negatively regulated by D-serine produced by osteoblasts. , J. Cell. Physiol., 227, 3477-3487, 2012.10.
11. Takahata Y., Takarada T., Hinoi E., Nakamura Y., Fujita H., Yoneda Y. , Osteoblastic GABAB receptors negatively regulate osteoblastogenesis toward disturbance of osteoclastogenesis mediated by receptor activator of nuclear factor-kB ligand in mouse bone. , J. Biol. Chem., 286, 32906-32917, 2011.09.
12. Nakamura Y.*, Hinoi E.*, Takarada T., Takahata Y., Yamamoto T., Fujita H., Takada S., Hashizume S., Yoneda Y., Positive regulation by GABABR1 subunit of leptin expression through gene transactivation in adipocytes., PLoS ONE. , 6, e20167, 2011.03.
13. Uno K., Takarada T., Takarada-Iemata M., Nakamura Y., Fujita H., Hinoi E., Yoneda Y. , Negative regulation of osteoblastogenesis through downregulation of runt-related transcription factor-2 in osteoblastic MC3T3-E1 cells with stable overexpression of the cystine/glutamate antiporter xCT subunit. , J. Cell. Physiol. , 226, 2953-2964, 2011.11.
14. Uno K., Takarada T., Nakamura Y., Fujita H., Hinoi E., Yoneda Y., A negative correlation between expression profiles of runt-related transcription factor-2 and cystine/glutamate antiporter xCT subunit in ovariectomized mouse bone. , J. Pharmacol. Sci. , 115, 309-319, 2011.02.
15. Takarada-Iemata M., Takarada T., Nakamura Y. Nakatani E., Hori O., Yoneda Y. , Glutamate preferentially suppresses osteoblastogenesis than adipogenesis through the cystine/glutamate antiporter in mesenchymal stem cells. , J. Cell. Physiol. , 226, 652-665, 2011.03.
16. Takahata Y., Takarada T., Osawa M., Hinoi E., Nakamura Y., Yoneda Y., Differential regulation of cellular maturation in chondrocytes and osteoblasts by glycine. , Cell Tissue Res. , 333, 91-103, 2008.07.
17. Nakamura Y.*, Takarada T.*, Kodama A., Hinoi E., Yoneda Y. , Predominant promotion by tacrolimus of chondrogenic differentiation to proliferating chondrocytes., J. Pharmacol. Sci. , 109, 413-423, 2009.03.