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Masaki Arioka Last modified date:2021.08.11

Assistant Professor / Department of Clinical Pharmacology
Research Center for Human Disease Modeling
Faculty of Medical Sciences




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Homepage
https://kyushu-u.pure.elsevier.com/en/persons/masaki-arioka
 Reseacher Profiling Tool Kyushu University Pure
Phone
092-642-6082
Fax
092-642-6084
Academic Degree
Doctor of Philosophy
Country of degree conferring institution (Overseas)
No
Field of Specialization
pharmacology, Oral and maxillofacial surgery
Total Priod of education and research career in the foreign country
02years03months
Research
Research Interests
  • Restoration of masticatory function in patients with osteoporosis by promoting alveolar bone healing using Liposomal-Wnt3a
    keyword : WNT-responsive cells, cell proliferation, osteogenesis, alveolar bone healing, tooth extraction, preclinical study
    2017.07~2020.12.
  • Evaluation: the anti-tumor and anti-metastatic activities of differentiation-inducing factor-1 on breast cancer
    keyword : cell proliferation, migration, invasion, cyclin D1、STAT3、EMT
    2017.04~2019.03.
  • Acceleration of bone regeneration by topical application of GSK-3 inhibitors

    keyword : GSK-3, Wnt/β-catenin signaling pathway
    2011.04~2014.04.
Academic Activities
Papers
1. Fumi Seto-Tetsuo, Masaki Arioka1, Koichi Miura, Takeru Inoue, Kazunobu Igawa, Katsuhiko Tomooka, Fumi Takahashi-Yanaga, Toshiyuki Sasaguri, DIF-1 inhibits growth and metastasis of triple-negative breast cancer through AMPK-mediated inhibition of the mTORC1-S6K signaling pathway, Oncogene, 2021.07, We have previously reported that the differentiation-inducing factor-1 (DIF-1), a compound identified in Dictyostelium discoideum, suppresses the growth of MCF-7 breast cancer cells by inactivating p70 ribosomal protein S6 kinase (p70S6K). Therefore, we first examined whether the same mechanism operates in other breast cancer cells, especially triple-negative breast cancer (TNBC), the most aggressive and refractory phenotype of breast cancer. We also investigated the mechanism by which DIF-1 suppresses p70S6K by focusing on the AMPK-mTORC1 system. We found that DIF-1 induces phosphorylation of AMPK and Raptor and dephosphorylation of p70S6K in multiple TNBC cell lines. Next, we examined whether AMPK-mediated inhibition of p70S6K leads to the suppression of proliferation and migration/infiltration of TNBC cells. DIF-1 significantly reduced the expression levels of cyclin D1 by suppressing the translation of STAT3 and strongly suppressed the expression levels of Snail, which led to the suppression of growth and motility, respectively. Finally, we investigated whether DIF-1 exerts anticancer effects on TNBC in vivo. Intragastric administration of DIF-1 suppressed tumor growth and spontaneous lung metastasis of 4T1-Luc cells injected into the mammary fat pad of BALB/c mice. DIF-1 is expected to lead to the development of anticancer drugs, including anti-TNBC, by a novel mechanism..
2. Masaki Arioka, Isaiah M. Dawid, Pedro L. Cuevas, Benjamin R. Coyac, Brian Leahy, Liao Wang, Xue Yuan, Zhijun Li, Xiaohui Zhang, Bo Liu, Jill A. Helms, Accelerating Socket Repair via WNT3A Curtails Alveolar Ridge Resorption, Journal of Dental Research, 2021.07, Tooth extraction triggers alveolar ridge resorption, and when this resorption is extensive, it can complicate subsequent reconstructive procedures that use dental implants. Clinical data demonstrate that the most significant dimensional changes in the ridge occur soon after tooth extraction. Here, we sought to understand whether a correlation existed between the rate at which an extraction socket heals and the extent of alveolar ridge resorption. Maxillary molars were extracted from young and osteoporotic rodents, and quantitative micro–computed tomographic imaging, histology, and immunohistochemistry were used to simultaneously follow socket repair and alveolar ridge resorption. Extraction sockets rapidly filled with new bone via the proliferation and differentiation of Wnt-responsive osteoprogenitor cells and their progeny. At the same time that new bone was being deposited in the socket, tartrate-resistant acid phosphatase–expressing osteoclasts were resorbing the ridge. Significantly faster socket repair in young animals was associated with significantly more Wnt-responsive osteoprogenitor cells and their progeny as compared with osteoporotic animals. Delivery of WNT3A to the extraction sockets of osteoporotic animals restored the number of Wnt-responsive cells and their progeny back to levels seen in young healthy animals and accelerated socket repair in osteoporotic animals back to rates seen in the young. In cases where the extraction socket was treated with WNT3A, alveolar ridge resorption was significantly reduced. These data demonstrate a causal link between enhancing socket repair via WNT3A and preserving alveolar ridge dimensions following tooth extraction..
3. masaki arioka, X. Zhang, Z. Li, U. S. Tulu, Y. Liu, L. Wang, X. Yuan, J. A. Helms, Osteoporotic Changes in the Periodontium Impair Alveolar Bone Healing, Journal of Dental Research, 10.1177/0022034518818456, 98, 4, 450-458, 2019.04, Osteoporosis is associated with decreased bone density and increased bone fragility, but how this disease affects alveolar bone healing is not clear. The objective of this study was to determine the extent to which osteoporosis affects the jaw skeleton and then to evaluate possible mechanisms whereby an osteoporotic phenotype might affect the rate of alveolar bone healing following tooth extraction. Using an ovariectomized mouse model coupled with micro–computed tomographic imaging, histologic, molecular, and cellular assays, we first demonstrated that the appendicular and jaw skeletons both develop osteoporotic phenotypes. Next, we demonstrated that osteoporotic mice exhibit atrophy of the periodontal ligament (PDL) and that this atrophy was accompanied by a reduction in the pool of osteoprogenitor cells in the PDL. The paucity of PDL-derived osteoprogenitor cells in osteoporotic mice was associated with significantly slower extraction socket healing. Collectively, these analyses demonstrate that the jaw skeleton is susceptible to the untoward effects of osteoporosis that manifest as thinner, more porous alveolar bone, PDL thinning, and slower bone repair. These findings have potential clinical significance for older osteopenic patients undergoing reconstructive procedures..
4. Masaki Arioka, Fumi Takahashi-Yanaga, Momoko Kubo, Kazunobu Igawa, Katsuhiko Tomooka, Toshiyuki Sasaguri, Anti-tumor effects of differentiation-inducing factor-1 in malignant melanoma: GSK-3-mediated inhibition of cell proliferation and GSK-3-independent suppression of cell migration and invasion, Biochemical Pharmacology, in press, 2017.05, Differentiation-inducing factor-1 (DIF-1) isolated from Dictyostelium discoideum strongly inhibits the proliferation of various mammalian cells through the activation of glycogen synthase kinase-3 (GSK-3). To evaluate DIF-1 as a novel anti-cancer agent for malignant melanoma, we examined whether DIF-1 has anti-proliferative, anti-migratory, and anti-invasive effects on melanoma cells using in vitro and in vivo systems. DIF-1 reduced the expression levels of cyclin D1 and c-Myc by facilitating their degradation via GSK-3 in mouse (B16BL6) and human (A2058) malignant melanoma cells, and thereby strongly inhibited their proliferation. DIF-1 suppressed the canonical Wnt signaling pathway by lowering the expression levels of transcription factor 7-like 2 and β-catenin, key transcription factors in this pathway. DIF-1 also inhibited cell migration and invasion, reducing the expression of matrix metalloproteinase-2; however, this effect was not dependent on GSK-3 activity. In a mouse lung tumor formation model, repeated oral administrations of DIF-1 markedly reduced melanoma colony formation in the lung. These results suggest that DIF-1 inhibits cell proliferation by a GSK-3-dependent mechanism and suppresses cell migration and invasion by a GSK-3-independent mechanism. Therefore, DIF-1 may have a potential as a novel anti-cancer agent for the treatment of malignant melanoma..
Presentations
1. Masaki Arioka, Xiaohui Zhang, Zhijun Li, U. Serdar Tulu, Yindong Liu, Liao Wang, Xue Yuan, Jill A. Helms, Osteoporotic changes in the periodontium impair alveolar bone healing, 97th International Association Dental Research/48th American Association Dental Research/43rd Canadian Association Dental Research, 2019.06, Background: Osteoporosis is associated with decreased bone density and increased bone fragility but how this disease impacts alveolar bone healing is not clear. The objective of this study was to determine the extent to which osteoporosis affects the jaw skeleton, and to evaluate possible mechanisms whereby an osteoporotic phenotype might affect the rate of alveolar bone healing following tooth extraction.
Methods: In the young group, the mice underwent a maxillary first molar tooth (mxM1) extraction at 8 weeks of age. In the osteoporosis group, 6-week-old mice underwent an ovariectomy (OVX) surgery. Eight weeks later, the mice underwent mxM1 extraction and were then followed until PED 1, 3, or 7. Using the Axin2CreERT2/+;R26RmTmG/+ lineage-tracing strain of mice, we delivered tamoxifen for three days before extraction then examined the distribution of Wnt-responsive cells and their progeny.
Results: We first demonstrated that the appendicular and jaw skeletons both develop osteoporotic phenotypes. Next, we demonstrated that osteoporotic mice exhibit atrophy of the periodontal ligament (PDL), and that this atrophy was accompanied by a reduction in the pool of osteoprogenitor cells in the PDL. Extraction stimulated cell proliferation: one major difference was that the number of mitotically active cells was significantly reduced at PED3, relative to the young cohort. Subsequently, as a result of delayed transition from cell proliferation to differentiation, the paucity of osteoprogenitor cells in osteoporotic mice was associated with significantly slower extraction socket healing. This shift in the proliferation/differentiation program was attributable to the Wnt-responsive population: there were significantly fewer Wnt-responsive cells in the extraction socket compared to the young group.
Conclusion: Collectively, these analyses demonstrate that the jaw skeleton is susceptible to the untoward effects of osteoporosis that manifest as thinner, more porous alveolar bone, PDL thinning, and slower bone repair. These findings have potential clinical significance for older osteopenic patients undergoing reconstructive procedures..
Membership in Academic Society
  • International Association of Dental Research
  • Japanese Cancer Association
  • Japanese Society of Clinical Pharmacology and Therapeutics
  • Japanese Pharmacological Society
  • Japanese Society of Oral and Maxillofacial Surgery
  • Japanese Society of Oral Implantology
Educational
Other Educational Activities
  • 2019.07.
  • 2019.05.
  • 2018.08.