Search for bone regeneration therapy by local administration of GSK-3 inhibitors

• Project/Area Number: 15K18990
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: General pharmacology
• Research Institution: Kyushu University
• Principal Investigator: ARIOKA Masaki 九州大学, 医学研究院, 助教 (20733554)
• Project Period (FY): 2015-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000); Fiscal Year 2016: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000); Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: GSK3 / GSK3阻害薬 / 炎症 / 骨再生 / 腎不全 / GSK阻害薬 / 破骨細胞

Outline of Final Research Achievements

SB216763 inhibited the strongest osteoclast differentiation. Moreover, the GSK3 inhibitors might inhibit osteoclast differentiation by suppressing the production of PBE2 through inhibition of COX-2 and mPGES-1. In response to the effect on osteoblasts, SB216763 resulted in promoting the most calcification.Although systemic administration of GSK3 inhibitors promotes bone formation, it was not known whether it is effective in patients with renal failure. Oral administration of lithium increases trabecular bone mass using adenine-induced uremic mice. It would be necessary to investigate the effect of other specific GSK3 inhibitors and study of the drug delivery system for local administration.Inhibiting activation of GSK3 would promote bone regeneration. On the other hand, we must also be concerned about the risk of cancer progression. Differentiation inducing factor-1, GSK3 activator, suppressed cancer proliferation / infiltration.

Research Products

• [Journal Article] Celecoxib inhibits osteoblast maturation by suppressing the expression of Wnt target genes (2017)
  • Author(s): Akihiro Nagano, Masaki Arioka, Fumi Takahashi, Etsuko Matsuzaki, Toshiyuki Sasaguri
  • Journal Title: Journal of Pharmacological Sciences Volume: 133 Issue: 1 Pages: 18-24
  • DOI: 10.1016/j.jphs.2016.11.003
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Celecoxib and 2,5-dimethylcelecoxib inhibit intestinal cancer growth by suppressing the Wnt/β-catenin signaling pathway (2017)
  • Author(s): I. Egashira, F. Takahashi-Yanaga, R. Nishida, M. Arioka, K. Igawa, K. Tomooka, Y. Nakatsu, T. Tsuzuki, Y. Nakabeppu, T. Kitazono, T. Sasaguri,
  • Journal Title: Cancer Science Volume: 108 Issue: 1 Pages: 108-115
  • DOI: 10.1111/cas.13106
  • Peer Reviewed / Open Access
• [Journal Article] 12,5-Dimethylcelecoxib prevents pressure-induced left ventricular remodeling through activation of GSK-3 (2017)
  • Author(s): Ai Fujita, Fumi Takahashi-Yanaga, Sachio Morimoto, Tatsuya Yoshihara, Masaki Arioka, Kazunobu Igawa, Katsuhiko Tomooka, Sumio Hoka, Toshiyuki Sasaguri
  • Journal Title: Hypertension Research Volume: 40 Issue: 2 Pages: 130-139
  • DOI: 10.1038/hr.2016.122
  • Peer Reviewed
• [Journal Article] A case of pediatric mandibular osteonecrosis caused by leakage of arsenic trioxide (2017)
  • Author(s): Masaki Arioka, Masanori Sasaki, Kotaro Ishii, Masaki Kanamoto, Takahiro Yamashiro, Yoshihide Mori
  • Journal Title: Japanese Journal of Oral and Maxillofacial Surgery Volume: 63 Issue: 1 Pages: 15-20
  • DOI: 10.5794/jjoms.63.15
  • NAID: 130005464698
  • ISSN: 0021-5163, 2186-1579
  • Peer Reviewed
• [Journal Article] Inhibition of GSK-3β increases trabecular bone volume but not cortical bone volume in adenine-induced uremic mice with severe hyperparathyroidism (2016)
  • Author(s): Narihito Tatsumoto, Masaki Arioka, Shunsuke Yamada, Fumi Takahashi-Yanaga, Masanori Tokumoto, Kazuhiko Tsuruya, Takanari Kitazono, Toshiyuki Sasaguri
  • Journal Title: Physiological Reports Volume: 4 Issue: 21
  • DOI: 10.14814/phy2.13010
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Inhibition of GSK-3 reduces prostaglandin E2 production by decreasing the expression levels of COX-2 and mPGES-1 in monocyte/macrophage lineage cells (2016)
  • Author(s): Toshihiro Noma, Fumi Takahashi, Masaki Arioka, Yoshihide Mori, Toshiyuki Sasaguri,
  • Journal Title: Biochemical Pharmacology Volume: 116 Pages: 121-129
  • DOI: 10.1016/j.bcp.2016.07.014
  • Peer Reviewed
• [Presentation] DIF-1 suppresses proliferation, migration and metastasis of malignant melanoma (2017)
  • Author(s): 有岡 将基, 高橋 富美, 笹栗 俊之
  • Organizer: 第90回日本薬理学会年会
  • Place of Presentation: 長崎
  • Year and Date: 2017-03-17
• [Presentation] 歯科インプラント埋入のための抜歯窩への炭酸リチウム局所単回投与の安全性および骨形成促進作用の評価 (2016)
  • Author(s): 有岡 将基, 高橋 富美, 佐々木匡理, 杉 友貴, 森 悦秀, 笹栗 俊之
  • Organizer: 第37回 日本臨床薬理学会学術総会
  • Place of Presentation: 米子
  • Year and Date: 2016-12-02
• [Presentation] The Anti-Calcific And Anti-Apoptotic Effects of GSK-3 Inhibitors In Cultured Human Aortic Smooth Muscle Cells (2016)
  • Author(s): Narihito Tatsumoto, Masaki Arioka, ShunsukeYamada, Masanori Tokumoto, Kazuhiko Tsuruya, Takanari Kitazono, Toshiyuki Sasaguri
  • Organizer: ASN kidney week 2016
  • Place of Presentation: Chicago
  • Year and Date: 2016-11-18
  • Int'l Joint Research
• [Presentation] DIF-1 suppresses proliferation, migration and metastasis of malignant melanoma (2016)
  • Author(s): Masaki Arioka, Fumi Takahashi-Yanaga, Toshiyuki Sasaguri
  • Organizer: 第75回日本癌学会学術総会
  • Place of Presentation: 横浜
  • Year and Date: 2016-10-07
• [Presentation] Increase in trabecular bone volume by inhibition of GSK-3beta in uremic mice (2016)
  • Author(s): 辰元為仁, 有岡将基, 山田俊輔, 徳本正憲, 鶴屋和彦, 北園孝成, 笹栗俊之
  • Organizer: 第89回 日本薬理学会年会
  • Place of Presentation: 横浜
  • Year and Date: 2016-03-09
• [Presentation] DIF-1はGSK-3βの活性化を介して悪性黒色腫に抗腫瘍効果をもたらす (2015)
  • Author(s): 有岡将基, 高橋富美, 笹栗俊之
  • Organizer: 第36回 日本臨床薬理学会学術総会
  • Place of Presentation: 東京
  • Year and Date: 2015-12-09
• [Presentation] GSK-3 阻害薬の NF- κ B を介した抗炎症薬としての可能性 (2015)
  • Author(s): 野間俊宏, 高橋富美, 有岡将基, 佐々木匡理, 笹栗俊之, 森悦秀
  • Organizer: 第69回日本口腔科学会学術集会
  • Place of Presentation: 大阪
  • Year and Date: 2015-05-13