Regulation of osteoclastogenesis by protein phosphatase 2C

• Project/Area Number: 20580105
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Applied biochemistry
• Research Institution: Chubu University
• Principal Investigator: OHNISHI Motoko Chubu University, 応用生物学部, 教授 (00312653)
• Co-Investigator(Kenkyū-buntansha): WOO JaeーTae 中部大学, 応用生物学部, 教授 (20272693) ; NAGAI Kazuo 中部大学, 応用生物学部, 教授 (00011974)
• Project Period (FY): 2008 – 2010
• Project Status: Completed (Fiscal Year 2010)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2010: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2009: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2008: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: プロテインホスファターゼ / 破骨細胞 / 破骨細胞分化因子 / シグナル伝達 / RANKL / プロティンホスファターゼ2C / 発生・分化 / 酵素 / 生理活性 / 細胞・組織

Research Abstract

Bone continuously undergoes remodeling, in which bone resorption by osteoclasts is followed by bone formation by osteoblasts, and maintains its structure and function. An imbalance in the regulation of bone remodeling results in many metabolic bone diseases, such as osteoporosis. Here we show that a low molecular weight compound which specifically activates protein phosphatase 2C(PP2C)suppressed osteoclastogenesis, and how it acts on the RANKL induced osteoclast differentiation.

Research Products

• [Journal Article] a β-carboline alkaloid, inhibits osteoclast differentiation and bone resorption in vitro and in vivo. (2011)
  • Author(s): Yonezawa T, Hasegawa S, Asai M, Ninomiya T, Sasaki T, Cha BY, Teruya T, Ozawa H, Yagasaki K, Nagai K, Woo JT
  • Journal Title: Eur J Pharmacol. 650(2-3) Pages: 511-8
  • Peer Reviewed
• [Journal Article] Harmine, a β-carboline alkaloid, inhibits osteoclast differentiation and bone resorption in vitro and in vivo. (2011)
  • Author(s): Takayuki Yonezawa
  • Journal Title: Eur J Pharmacol. Volume: 650 Pages: 511-518
  • Peer Reviewed
• [Journal Article] Identification of oxytetracycline as a chondrogenic compound using a cell-based screening system. (2010)
  • Author(s): Hojo H, Yano F, Ohba S, Igawa K, Nakajima K, Komiyama Y, Kan A, Ikeda T, Yonezawa T, Woo JT, Takato T, Nakamura K, Kawaguchi H, Chung UI
  • Journal Title: J Bone Miner Metab. 28(6) Pages: 627-33
  • Peer Reviewed
• [Journal Article] Palmatine attenuates osteoclast differentiation and function through inhibition of receptor activator of nuclear factor-κb ligand expression in osteoblast cells. (2010)
  • Author(s): Lee JW, Mase N, Yonezawa T, Seo HJ, Jeon WB, Cha BY, Nagai K, Woo JT
  • Journal Title: Biol Pharm Bull. 33(10) Pages: 1733-9
  • Peer Reviewed
• [Journal Article] Alisol-B, a novel phyto-steroid, suppresses the RANKL-induced osteoclast formation and prevents bone loss in mice. (2010)
  • Author(s): Lee JW, Kobayashi Y, Nakamichi Y, Udagawa N, Takahashi N, Im NK, Seo HJ, Jeon WB, Yonezawa T, Cha BY, Woo JT
  • Journal Title: Biochem Pharmacol. 80 Pages: 352-361
  • Peer Reviewed
• [Journal Article] Pisiferdiol and pisiferic acid isolated from Chamaecyparispisifera activate protein phosphatase2C in vitro and induce caspase-3/7-dependentapoptosis via dephosphorylation of Bad in HL60 cells. (2010)
  • Author(s): Aburai N., Yoshida M., Ohnishi M., Kimura K.
  • Journal Title: Phytomedicine. 17(10) Pages: 782-788
  • Peer Reviewed
• [Journal Article] Honokiol increases ABCA1 expression level by activating retinoid X receptor beta. (2010)
  • Author(s): Jung CG, Horike H, Cha BY, Uhm KO, Yamauchi R, Yamaguchi T, Hosono T, Iida K, Woo JT, Michikawa M
  • Journal Title: Biol Pharm Bull. 33(7) Pages: 1105-11
  • Peer Reviewed
• [Journal Article] 植物由来のプロテインホスファターゼ2C活性制御物質 (2010)
  • Author(s): 油井信弘,大西素子,木村賢一
  • Journal Title: バイオサイエンスインダストリー 68(4) Pages: 256-256
  • NAID: 10026883285
• [Journal Article] Sanguinarine as a Potent and Specific Inhibitor of Protein Phosphatase 2C in Vitro and Induces Apoptosis via Phosphorylation of p38 in HL60 Cells. (2010)
  • Author(s): Aburai N, Yoshida M, Ohnishi M, Kimura K
  • Journal Title: Biosci Biotechnol Biochem. 74(3) Pages: 548-552
  • Peer Reviewed
• [Journal Article] Honokiol inhibits osteoclast differentiation and function in vitro. (2010)
  • Author(s): Hasegawa S, Yonezawa T, Ahn JY, Cha BY, Teruya T, Takami M, Yagasaki K, Nagai K, Woo JT
  • Journal Title: Biol Pharm Bull. 33(3) Pages: 487-92
  • NAID: 130000248103
  • Peer Reviewed
• [Journal Article] Phytochemicals that stimulate osteoblastic differentiation and bone formation. (2010)
  • Author(s): Woo JT , Yonezawa T, Nagai K
  • Journal Title: J Oral Biosci. 52(1) Pages: 15-21
  • NAID: 10027105179
  • Peer Reviewed
• [Journal Article] Pisiferdiol and pisiferic acid isolated from Chamaecyparispisifera activate protein phosphatase2C in vitro and induce caspase-3/7-dependentapoptosis via dephosphor ylation of Bad in HL60 cells. (2010)
  • Author(s): Nobuhiro Aburai
  • Journal Title: Phytomedicine Volume: 17 Pages: 782-788
  • Peer Reviewed
• [Journal Article] Sanguinarine as a Potent and Specific Inhibitor of Protein Phosphatase 2C in vitro and Induces Apoptosis via Phosphorylation of p38 in HL60 Cells. (2010)
  • Author(s): Nobuhiro Aburai
  • Journal Title: Biosci Biotechnol Biochem Volume: 74 Pages: 548-552
  • Peer Reviewed
• [Journal Article] 植物由来のプロテインホスファターゼ2C活性制御物質 (2010)
  • Author(s): 油井信弘
  • Journal Title: バイオサイエンスインダストリー Volume: 68 Pages: 256-258
• [Journal Article] Palmatine attenuates osteoclast differentiation and function through inhibition of receptor activator of nucleaz factor-κb ligand exression in osteoblast cells. (2010)
  • Author(s): Ji-Won Lee
  • Journal Title: Biol Pharm Bull. Volume: 33 Pages: 1733-1739
  • Peer Reviewed
• [Journal Article] Honokiol increases ABCA1 expression level by activating retinoid X receptor beta. (2010)
  • Author(s): Cha-Gyun Jung
  • Journal Title: Biol Pharm Bull. Volume: 33 Pages: 1105-1111
  • Peer Reviewed
• [Journal Article] Alisol-B, a novel phyto-steroid, suppresses the RANKL-induced osteoclast formation and prevents bone loss in mice. (2010)
  • Author(s): Ji-Won Lee
  • Journal Title: Biochem Pharmacol. Volume: 80 Pages: 352-361
  • Peer Reviewed
• [Journal Article] Identification of oxytetracycline as a chondrogenic compound using a cell-based screening system. (2010)
  • Author(s): Hironori Hojo
  • Journal Title: J Bone Miner Metab. Volume: 28 Pages: 627-633
  • Peer Reviewed
• [Journal Article] Phytochemicals that stimulate osteoblastic differentiation and bone formation. (2010)
  • Author(s): Je-Tae Woo
  • Journal Title: J Oral Biosci. Volume: 52 Pages: 15-21
  • Peer Reviewed
• [Journal Article] Pisiferdiol and pisiferic acid isolated from Chamaecyparis pisifera activate protein phosphatase 2C in vitro and induce caspase-3/7-dependent apoptosis via dephosp horylation of Bad in HL60 cells (2010)
  • Author(s): Aburai N.
  • Journal Title: Phytomedicine (in press)
  • Peer Reviewed
• [Journal Article] Sanguinarine as a potent and specific inhibitor of protein phosphatase 2C in vitro and induces apoptosis via phosphorylation of p38 in HL60 cells (2010)
  • Author(s): Aburai N.
  • Journal Title: Biosci Biotechnol Biochem 74 Pages: 548-552
  • Peer Reviewed
• [Journal Article] Honokiol inhibits osteoclast differentiation and function in vitro (2010)
  • Author(s): Hasegawa S.
  • Journal Title: Biol Pharm Bull 51 Pages: 487-492
  • Peer Reviewed
• [Journal Article] Magnolol enhances adipocyte differentiation and glucose uptake in 3T3-L1 cells. (2009)
  • Author(s): Choi SS, Cha BY, Lee YS, Yonezawa T, Teruya T, Nagai K, Woo JT
  • Journal Title: Life Sci. 84(25-26) Pages: 908-14
  • Peer Reviewed
• [Journal Article] An inhibitory effect of chrysoeriol on platelet-derived growth factor (PDGF)-induced proliferation and PDGF receptor signaling in human aortic smooth muscle cells. (2009)
  • Author(s): Cha BY, Shi WL, Yonezawa T, Teruya T, Nagai K, Woo JT
  • Journal Title: J Pharmacol Sci. 110(1) Pages: 105-10
  • NAID: 10025736841
  • Peer Reviewed
• [Journal Article] Inhibitory effect of luteolin on osteoclast differentiation and function (2009)
  • Author(s): Lee JW.
  • Journal Title: Cytotechnology 61 Pages: 125-134
  • Peer Reviewed
• [Journal Article] プロテインチップを用いた朝刊出血性大腸菌O-157:H7由来べろ毒素の高感度検出法 (2009)
  • Author(s): 田辺りま
  • Journal Title: 食品衛生学雑誌 51 Pages: 28-31
  • Peer Reviewed
• [Journal Article] Magnolol enhances adipocyte differentiation and glucose uptake in 3T3-L1 cells (2009)
  • Author(s): Choi SS.
  • Journal Title: Life Sci. 84 Pages: 908-914
  • Peer Reviewed
• [Journal Article] An inhibitory effect of chrysoeriol on platelet-derived growth factor(PDGF)-induced proliferation and PDGF receptor signaling in human aortic smooth muscle cells (2009)
  • Author(s): Cha BY.
  • Journal Title: J Pharmacol Sci 110 Pages: 105-110
  • Peer Reviewed
• [Journal Article] Development of high-throughput screening system for osteogenic drugs using a cell-based sensor. (2008)
  • Author(s): Hojo H, Igawa K, Ohba S, Yano F, Nakajima K, Komiyama Y, Ikeda T, Lichtler AC, Woo JT, Yonezawa T, Takato T, Chung UI
  • Journal Title: Biochem Biophys Res Commun. 376(2) Pages: 375-9
  • Peer Reviewed
• [Journal Article] Antiresorptive microbial compounds that inhibit osteoclast differentiation, function and survival. (2008)
  • Author(s): Woo JT, Yonezawa T, Cha BY, Teruya T, Nagai K
  • Journal Title: J Pharmacol Sci. 106(4) Pages: 547-554
  • Peer Reviewed
• [Journal Article] Antiresorptive microbial compounds that inhibit osteoclastdifferentiation, function and survival. (2008)
  • Author(s): Woo JT
  • Journal Title: J Pharmacol Sci. 106 Pages: 547-554
  • Peer Reviewed
• [Journal Article] Safety and effectiveness studies of propolis. (2008)
  • Author(s): Lee YS
  • Journal Title: Assoc J Jpn Soc Med Use Func Food 5 Pages: 135-142
  • Peer Reviewed
• [Journal Article] Development of high-throughput screening system for osteogenicdrugs using a cell-based sensor. (2008)
  • Author(s): Hojo H
  • Journal Title: Biochem Biophys Res Commun. 376 Pages: 375-379
  • Peer Reviewed
• [Presentation] PP2C活性化物質pisiferdiolのCa2+シグナル伝達に関わる遺伝子変異酵母に対する作用メカニズムの解析 (2010)
  • Author(s): 油井信弘
  • Organizer: 第5回ケミカルバイオロジー学会
  • Place of Presentation: 慶応義塾大学
  • Year and Date: 2010-05-19
• [Presentation] PP2C活性化物質PisiferdiolのCa^<2+>シグナル伝達に関わる遺伝子変異酵母に対する作用メカニズムの解析 (2010)
  • Author(s): 油井信弘
  • Organizer: 日本ケミカルバイオロジー学会 第5回年会
  • Place of Presentation: 慶応義塾大学(神奈川県)
  • Year and Date: 2010-05-19
• [Presentation] 破骨細胞分化におけるプロテインホスファターゼ2Cεの機能 (2010)
  • Author(s): 倉地建始
  • Organizer: 日本農芸化学会2010年度大会
  • Place of Presentation: 東京大学
  • Year and Date: 2010-03-29
• [Presentation] 破骨細胞分化におけるプロテインボスファターゼ2Cεの機能 (2010)
  • Author(s): 倉地建始
  • Organizer: 日本農芸化学会2010年度大会
  • Place of Presentation: 東京大学(東京)
  • Year and Date: 2010-03-29
• [Presentation] 卵巣摘出マウスの骨密度低下に対するホノキオールの抑制効果 (2010)
  • Author(s): 浅井みどり
  • Organizer: 日本農芸化学会2010年度大会
  • Place of Presentation: 東京大学(東京)
  • Year and Date: 2010-03-29
• [Presentation] PP2C活性化物質Pisiferdiolと阻害物質Sanguinarineの癌細胞と遺伝子変異酵母に対する生物活性 (2009)
  • Author(s): 油井信弘
  • Organizer: The 25th NAITO CONFERENCE ON Chemical Biology [II]-An Emerging Field Inspired by Natural Product Chemistry-
  • Place of Presentation: シャトレーゼガトーキングダム札幌
  • Year and Date: 2009-09-10
• [Presentation] PP2C活性化物質 Pisiferdiol と阻害物質 Sanguinarine の癌細胞と遺伝子変異酵母に対する生物活 (2009)
  • Author(s): 油井信弘
  • Organizer: 第25回内藤コンファレンス
  • Place of Presentation: シャトレーゼガトーキングダム札幌(札幌)
  • Year and Date: 2009-09-10
• [Presentation] 破骨細胞分化に対する Pisiferdiol の作用 (2009)
  • Author(s): 倉知建始
  • Organizer: 第27回日本骨代謝学会
  • Place of Presentation: 大阪国際会議場(大阪)
  • Year and Date: 2009-07-25
• [Presentation] プロテインホスファターゼ2C活性化化合物の破骨細胞分化抑制機構の解析 (2009)
  • Author(s): 吉田真実
  • Organizer: 日本農芸化学会2009年度大会
  • Place of Presentation: 福岡・マリンメッセ福岡
  • Year and Date: 2009-03-28
• [Presentation] Pisiferdiol and Pisiferic Acid Isolated from Chamaecyparis pisiferaare Activators of Protein Phosphatase 2C. (2009)
  • Author(s): 油井信弘
  • Organizer: 日本農芸化学会2009年度大会
  • Place of Presentation: 福岡・マリンメッセ福岡
  • Year and Date: 2009-03-28
• [Presentation] プロテインホスフアターゼ2C活性化化合物の破骨細胞分化抑制機構の解析 (2009)
  • Author(s): 吉田真実
  • Organizer: 日本農芸化学会2009年度大会
  • Place of Presentation: 福岡・マリンメッセ福岡
  • Year and Date: 2009-03-28
• [Presentation] プロテインホスファターゼ2C活性化化合物による破骨細胞分化の抑制 (2008)
  • Author(s): 吉田真実
  • Organizer: 第31回年会
  • Place of Presentation: 兵庫・神戸ポートアイランド
  • Year and Date: 2008-12-11
• [Presentation] プロテインホスフアターゼ2C活性化化合物による破骨細胞分化の抑制 (2008)
  • Author(s): 吉田真実
  • Organizer: 日本分子生物学会第31回年会
  • Place of Presentation: 兵庫・神戸ポートアイラン
  • Year and Date: 2008-12-11
• [Presentation] Suppression of osteoclast differentiation by pisiferdiol, an activator of protein phosphatase 2C. (2008)
  • Author(s): 吉田真実
  • Organizer: 8th International Conference on Protein Phosphatases.
  • Place of Presentation: GUNMA・MAEBASHI TERRSA
  • Year and Date: 2008-11-13
• [Presentation] Suppression of osteoclast differentiation by pisiferdiol, an activatorof protein phosphatase 2C. (2008)
  • Author(s): Mami Yoshida
  • Organizer: 8th International Conference on Protein Phosphatases.
  • Place of Presentation: Gunma・Maebashi Terusa.
  • Year and Date: 2008-11-13
• [Presentation] Pisiferdiol and Pisiferic Acid Isolated from Chamaecyparis pisiferaare Activators of Protein Phosphatase 2C. (2008)
  • Author(s): Nobuhiro Aburai
  • Organizer: 2008 IU-UGAS/IU-GSA/IU-COE Joint Symposium
  • Place of Presentation: Iwate・Aiina Center
  • Year and Date: 2008-10-27
• [Presentation] PP2C活性化作用を有する化合物の構造と機能性 (2008)
  • Author(s): 油井信弘
  • Organizer: 日本ケミカルバイオロジー学会第3回年会
  • Place of Presentation: 東京・学術総合センター
  • Year and Date: 2008-05-19
• [Remarks] ホームページ等
  • URL: http://www3.chubu.ac.jp/faculty/ohnishi_motoko
• [Patent(Industrial Property Rights)] 破骨細胞分化抑制剤 (2008)
  • Inventor(s): 大西素子、永井和夫、禹済泰、木村賢一
  • Industrial Property Rights Holder: 学校法人中部大学、国立大学法人岩手大学
  • Industrial Property Number: 2008-219666
  • Filing Date: 2008-08-28
• [Patent(Industrial Property Rights)] 骨吸収抑制剤 (2008)
  • Inventor(s): 大西素子, 木村賢一, 萬済泰, 永井和夫.
  • Industrial Property Rights Holder: 中部大学, 岩手大学
  • Industrial Property Number: 2008-219666
  • Filing Date: 2008-08-28