Inhibition of bone destruction by phosphatidylserine-containing liposomes based on t he regulation of phagocytes functions

2010 Fiscal Year Final Research Report

• Project/Area Number: 20390472
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Functional basic dentistry
• Research Institution: Kyushu University
• Principal Investigator: HIROSHI Nakanishi Kyushu University, 大学院・歯学研究院, 教授 (20155774)
• Co-Investigator(Kenkyū-buntansha): TAKE Hiro 九州大学, 大学院・歯学研究院, 准教授 (10420598)
• Project Period (FY): 2008 – 2010
• Keywords: リポソーム / 炎症性骨吸収 / 骨芽細胞 / 破骨細胞 / ホスファチジルセリン

Research Abstract

This study investigated the effects of phosphatidylserine-containing liposomes (PSLs) on the osteoclastogenesis. In the rat bone marrow culture system, osteoclast precursors phagocytosed PSLs to secrete TGF-β1and PGE2, which in turn inhibited osteoclastogenesis through the downregulation of receptor activator for NF-κB ligand, receptor activator of NF-κB. Consistent with these in vitro observations, i.m. injection of PSLs significantly increased the plasma level of TGF-β1 and PGE2 and decreased the expression of receptor activator for NF-κB ligand, receptor activator of NF-κB the skeletal tissues of ankle joints of rats with adjuvant arthritis. Together with the inhibitory effects on osteoclastogenes, PSLs are involved in regulation of bone remodeling. Because PS is a component of the cell membrane, PSLs therefore can be a potentially effective pharmacological intervention against abnormal bone loss, such as osteoporosis without deleterious side effects.

Research Products

• [Journal Article] Phosphatidylserine-containing liposomes : potential pharmacological interventions against inflammatory and immune diseases through the production of prostaglandin E_2 after uptake by myeloid derived phagocytes (2011)
  • Author(s): Wu Z, Nakanishi H
  • Journal Title: Ach.Immunol.Therap.Exp. 59 Pages: 196-201
• [Journal Article] Phosphatidylserine-containing liposomes inhibit the differentiation of osteoclasts and trabecular bone loss. (2010)
  • Author(s): Wu Z, Ma HM, Kukita T, Nakanishi Y, Nakanishi H.
  • Journal Title: J Immunol. 15;184(6) Pages: 3191-3201
• [Journal Article] Involvement of cathepsin B in the processing and secretion of interleukin-1β in chromogranin A-stimulated microglia. (2010)
  • Author(s): Terada K, Yamada J, Hayashi Y, Wu Z, Uchiyama Y, Peters C, Nakanishi H.
  • Journal Title: Glia. 58(1) Pages: 114-124
• [Journal Article] Acute p38-mediated inhibition of NMDA-induced outward currents in hippocampal CA1 neurons by interleukin-1β. (2010)
  • Author(s): Zhang R, Sun L, Hayashi Y, Liu X, Koyama S, Wu Z, Nakanishi H.
  • Journal Title: Neurobiol Dis. 38(1) Pages: 68-77
• [Journal Article] Cathepsin B-dependent motor neuron death after nerve injury in the adult mouse. (2010)
  • Author(s): Sun L, Wu Z, Baba M, Peters C, Uchiyama Y, Nakanishi H.
  • Journal Title: Biochem Biophys Res Commun. 399(3) Pages: 391-395
• [Journal Article] Age-dependent responses of glial cells and leptomeninges during systemic inflammation. (2008)
  • Author(s): Wu Z, Tokuda Y, Zhang XW, Nakanishi H.
  • Journal Title: Neurobiol.Disease 32 Pages: 543-551
• [Journal Article] Reverse of brain aging by an overexpression of human mitochondrial transcription factor A in mice. (2008)
  • Author(s): Hayashi Y, Yoshida M, Yamato M, Ide T, Wu Z, Ochi-Shindou M, Kanki T, Kang D, Sunagawa K, Tsutsui H, Nakanishi H.
  • Journal Title: J.Neurosci. 28 Pages: 8624-8634
• [Journal Article] Possible involvement of cathepsin B released by microglia in methylmercury -induced cerebellar pathological changes in the adult rats. (2008)
  • Author(s): Sakamoto M, Miyamoto KI, Wu Z, Nakanishi H.
  • Journal Title: Neurosci.Lett. 442 Pages: 292-296
• [Journal Article] Inhibition of NMDA-induced outward currents by interleukin-1β in hippocampal neurons. Biochem. (2008)
  • Author(s): Zhang R, Yamada J, Hayashi Y, Wu Z, Koyama S, Nakanishi H.
  • Journal Title: Biophys.Res.Commun. 372 Pages: 816-820
• [Journal Article] Reduced synaptic acticity precedes synaptic stripping in vagal motoneurons after axotomy. (2008)
  • Author(s): Yamada J, Hayashi Y, Jinno S, Wu Z, Inoue K, Kohsaka S, Nakanishi H.
  • Journal Title: Glia 56 Pages: 1148-1462
• [Journal Article] Microglia-aging : Roles of microglial lysosome- and mitochondria-derived reactive oxygen species in brain aging. Behav.
  • Author(s): Nakanishi H, Wu Z.
  • Journal Title: Brain Res.
• [Presentation] 中年ルイスラットにおけるアジュバント関節炎に伴うミクログリア活性化と海馬長期増強の障害 (2010)
  • Author(s): 武洲、劉霞、中西博
  • Organizer: 第63回日本薬理学会西南部会
  • Place of Presentation: 鹿児島
  • Year and Date: 2010-11-26
• [Presentation] S-ケタミンのNMDA電流ならびにミクログリア活性化の優位阻害による神経障害性疼痛に対する抑制作用 (2010)
  • Author(s): 林良憲、河路広大、中西博
  • Organizer: 第63 回日本薬理学会西南部会
  • Place of Presentation: 鹿児島
  • Year and Date: 2010-11-26
• [Presentation] A possible involvement of cathepsin B in nociceptive processing through the processing and secretion of interleukin-1 family from microglia. (2010)
  • Author(s): Sun L, Wu Z, Hayashi Y, Nakanishi H
  • Organizer: Neuroscience 2010
  • Place of Presentation: サンジエゴ
  • Year and Date: 2010-11-14
• [Presentation] Acute p38-mediated inhibition of K_Ca channels activated by Ca^<2+> influx through both NMDA receptor and voltage-gated Ca^<2+> channels by interleukin-1β (2010)
  • Author(s): Hayashi Y, Zhang R, Sun L, Wu Z, Nakanishi H
  • Organizer: Neuroscience 2010
  • Place of Presentation: サンジエゴ
  • Year and Date: 2010-11-14
• [Presentation] S-ketamine preferentially inhibits neuropathic pain through the neuronal-based and microglia-related mechanisms. (2010)
  • Author(s): Kawaji K, Hayashi Y, Nakanishi H
  • Organizer: Neuroscience 2010
  • Place of Presentation: サンジエゴ
  • Year and Date: 2010-11-14
• [Presentation] ミクログリアの産生するカテプシンS の神経障害性疼痛発症における役割 (2010)
  • Author(s): 張馨文、林良憲、武洲、中西 博
  • Organizer: 第15回グリア研究会
  • Place of Presentation: 福岡
  • Year and Date: 2010-10-23
• [Presentation] ミクログリアの産生するカテプシンBの炎症性疼痛発症における役割 (2010)
  • Author(s): 孫麗、武洲、中西博
  • Organizer: 第15回グリア研究会
  • Place of Presentation: 福岡
  • Year and Date: 2010-10-23
• [Presentation] Differebtial inolvement of astrocytes and microglia in neuronal survival after hypoglossal nerve injury. (2010)
  • Author(s): Yamada J, Jinno S, Nakanishi H
  • Organizer: The 29^<th> Naito Conference : Glia World.
  • Place of Presentation: 湘南村
  • Year and Date: 2010-10-05
• [Presentation] Preferential inhibitory effects of S-ketamine on neuropatic pain through both the neuronal based and microglia related mechanisms. (2010)
  • Author(s): Hayashi Y, Kawaji K, Nakanishi H
  • Organizer: The 29^<th> Naito Conference : Glia World.
  • Place of Presentation: 湘南村
  • Year and Date: 2010-10-05
• [Presentation] 炎症性疼痛発症におけるミクログリアのカテプシンBの関与 (2010)
  • Author(s): 孫麗、武洲、中西博
  • Organizer: 第52回歯科基礎医学会学術大会
  • Place of Presentation: 東京
  • Year and Date: 2010-09-20
• [Presentation] 神経障害性疼痛におけるミクログリアのカテプシンSの関与 (2010)
  • Author(s): 張馨文、孫麗、武洲、中西博
  • Organizer: 第52回歯科基礎医学会学術大会
  • Place of Presentation: 東京
  • Year and Date: 2010-09-20
• [Presentation] 慢性末梢炎症によるミクログリア活性化と海馬LTP障害 (2010)
  • Author(s): 劉霞、武洲、中西博
  • Organizer: 第52回歯科基礎医学会学術大会
  • Place of Presentation: 東京
  • Year and Date: 2010-09-20
• [Presentation] ホスファチジルセリンリポソームによる炎症性骨破壊抑制メカニズムの解析 (2010)
  • Author(s): 武洲、馬紅梅、久木田敏夫、中西博
  • Organizer: 第52回歯科基礎医学会学術大会
  • Place of Presentation: 東京
  • Year and Date: 2010-09-20
• [Presentation] ホスファチジルセリンリポソームによる骨形成の促進 (2010)
  • Author(s): 馬紅梅、武洲、李銀姫、久木田敏夫、中西博
  • Organizer: 第52回歯科基礎医学会学術大会
  • Place of Presentation: 東京
  • Year and Date: 2010-09-20
• [Presentation] Protective effects of microglia-conditioned medium against NMDA-induced dendritic injury through an inhibition of non-selective cation conductance. (2010)
  • Author(s): Hayashi Y, Fujita S, Odagaki Y, Shinagawa R, Kagamiishi Y, Nakanishi H
  • Organizer: Neuro2010
  • Place of Presentation: 神戸
  • Year and Date: 2010-09-02
• [Presentation] Preferential inhibitory effects of S-ketamine on both NMDA receptor currents and neuropathic pain. (2010)
  • Author(s): Kawaji K, Hayshi Y, Koyano K, Yokoyama T, Nakanishi H
  • Organizer: Neuro2010
  • Place of Presentation: 神戸
  • Year and Date: 2010-09-02
• [Presentation] Reverse of the rheumatoid arthritis-induced acceleration of brain aging in the middle age by minocycline. (2010)
  • Author(s): 武洲, 劉霞, 中西博
  • Organizer: The 1^<st> International Congress on Controversies in Longevity, Health and Aging.
  • Place of Presentation: バルセロナ
  • Year and Date: 2010-06-24
• [Presentation] Microglial cathepsin B : A strategic target for neuroprotective agents. (2010)
  • Author(s): 武洲, 中西博
  • Organizer: BIT's Inaugural Symposium on Enzyme & Biocatalysis-2010.
  • Place of Presentation: 上海
  • Year and Date: 2010-04-22
• [Presentation] ミクログリアのリソソーム・ミトコンドリア系を標的としたグリア創薬に可能性 (2010)
  • Author(s): 中西博
  • Organizer: 第130回日本薬学会年会、130回年会祈念融合型シンポジウム「グリア創薬の最前線と可能性」
  • Place of Presentation: 岡山
  • Year and Date: 2010-03-29
• [Presentation] Neuroprotection of microglia-conditioned medium on excitotoxic neuronal injury through inhibition of large cation conductance. (2010)
  • Author(s): Hayashi Y, Fujita S, Odagaki Y, Shinagawa R, Kagamiishi Y, Nakanishi H
  • Organizer: 第83回日本薬理学会年会
  • Place of Presentation: 大阪
  • Year and Date: 2010-03-16
• [Presentation] カテプシンB阻害による疼痛制御 (2010)
  • Author(s): 中西博
  • Organizer: 第5回九大痛みの研究会
  • Place of Presentation: 福岡
  • Year and Date: 2010-02-19
• [Presentation] Involvement of cathepsin B in the processing and secretion of interleukin-1β in chromogranin A-stimulated microglia. (2009)
  • Author(s): Nakanishi H, Terada K, Yamada J, Hayashi Y, Wu Z
  • Organizer: 第82回日本薬理学会年会
  • Place of Presentation: 横浜
  • Year and Date: 20090300
• [Presentation] ミクログリアのニューロン保護作用:NMDA誘発こうフィン毒性に対するミクログリア培養上清の保護メカニズムの解析 (2009)
  • Author(s): 林良憲、中西博
  • Organizer: 第62回日本薬理学会西南部会
  • Place of Presentation: 愛媛
  • Year and Date: 2009-11-27
• [Presentation] インターロイキン-1βのp38MAPキナーゼの活性化を介したNMDAにより惹起されるCa^<2+>活性化K^+電流の抑制作用 (2009)
  • Author(s): Zhang R, 劉霞、孫麗、林良憲、武洲、中西博
  • Organizer: 第62回日本薬理学会西南部会
  • Place of Presentation: 愛媛
  • Year and Date: 2009-11-27
• [Presentation] 末梢炎症によるミクログリア活性化と脳老化の促進 (2009)
  • Author(s): 武洲、劉霞、中西博
  • Organizer: 第14回グリア研究会
  • Place of Presentation: 大阪
  • Year and Date: 2009-11-14
• [Presentation] 運動神経軸索切断後のアストロサイト形態・ミクログリアの形態の比較検討 (2009)
  • Author(s): 山田純、神野尚三、中西博
  • Organizer: 第14回グリア研究会
  • Place of Presentation: 大阪
  • Year and Date: 2009-11-14
• [Presentation] 末梢炎症により惹起される脳炎症の老化による増悪:鍵を握る脳の免疫担当細胞ミクリグリアの動態について (2009)
  • Author(s): 中西博
  • Organizer: 第52回秋期日本歯周病学術大会、シンポジウム「歯周組織の免疫応答から考える全身への影響」
  • Place of Presentation: 宮崎
  • Year and Date: 2009-10-11
• [Presentation] Age-dependent differential phenotypic changes of glial cells by systemic inflammation. (2009)
  • Author(s): 武洲, 中西博
  • Organizer: 9^<th> European Meeting on Glial Cells in Health and Disease.
  • Place of Presentation: パリ
  • Year and Date: 2009-09-10
• [Presentation] Extracellular nucleotide-mediated reduced synaptic activity precedes microglial synaptic stripping after an axotomy. International Symposium on Purinergic Signalling in New Strategy of Drig Discovery (2009)
  • Author(s): 中西博, 山田純
  • Organizer: Fukuoka Purine 2009
  • Place of Presentation: 福岡
  • Year and Date: 2009-07-24
• [Presentation] Microglia-aging : Roles of microglial lysosome-and mitochondria-derived reactive oxygen species in brain aging. (2009)
  • Author(s): 中西博
  • Organizer: 第52回日本神経化学会、シンポジウム「ミクログリアの機能と病態-最近の研究動向と将来の展望-」
  • Place of Presentation: 群馬県伊香保
  • Year and Date: 2009-06-24
• [Presentation] Age-dependent differential microglial and astrocytic responses through leptomeninges during systemic inflammation. (2009)
  • Author(s): Wu Z, Tokuda Y, Zhang XW, Nakanishi H
  • Organizer: 第82回日本薬理学会年会
  • Place of Presentation: 横浜
  • Year and Date: 2009-03-16
• [Presentation] Involvement of p38 MAPK in interleukin-1β-induced inhibition of NMDA-induced outward currents in hippocampal neurons. (2008)
  • Author(s): Zhang R, Nakanshi H.
  • Organizer: Berlin Brain Days
  • Place of Presentation: ベルリン
  • Year and Date: 2008-12-10
• [Presentation] ミトコンドリア転写因子Aの過剰発現によるミトコンドリア内レドックス制御ならびに老化に伴う脳機能低下の制御 (2008)
  • Author(s): 中西博、林良憲、井手友美、武洲
  • Organizer: 第61回日本薬理学会西南部会
  • Place of Presentation: 米子
  • Year and Date: 2008-11-28
• [Presentation] 末梢炎症に対する髄膜-グリア連関の汎脳性の老化に伴う変容 (2008)
  • Author(s): 武洲、中西博
  • Organizer: 第61回日本薬理学会西南部会
  • Place of Presentation: 米子
  • Year and Date: 2008-11-28
• [Presentation] Age-dependent differentiatial regulation of tight junction proteins in the leptomeninges by glial cells during systemic inflammation. (2008)
  • Author(s): 武洲, 中西博
  • Organizer: Neuroscience 2008
  • Place of Presentation: ワシントンDC
  • Year and Date: 2008-11-23
• [Presentation] Involvement of cathepsin B in the processing and secretion of interleukin-1β in chromogranin A-stimulated microglia. (2008)
  • Author(s): Nakanishi H, Terada K, Yamada J, Hayashi Y, Wu Z
  • Organizer: Neuroscience 2008
  • Place of Presentation: ワシントンDC
  • Year and Date: 2008-11-23
• [Presentation] Reduced synaptic activity mediated by extracellular nucleotides precedes synaptic stripping after an axotomy. (2008)
  • Author(s): Yamada J, Jinno S, Nakanishi H
  • Organizer: Neuroscience 2008
  • Place of Presentation: ワシントンDC
  • Year and Date: 2008-11-23
• [Presentation] Overexpression of human TFAM prevents age-dependent memory impairement in mice by suppression of mitochondrial oxidative stress. (2008)
  • Author(s): Hayashi Y, Yoshida M, Yamato M, Ide T, Wu Z, Nakanishi H
  • Organizer: Neuroscience 2008
  • Place of Presentation: ワシントンDC
  • Year and Date: 2008-11-23
• [Presentation] TFAM過剰発現によるミクログリア内レドックス制御と老化に伴う脳機能低下の防止 (2008)
  • Author(s): 林良憲、井手友美、中西博
  • Organizer: 第13回グリア研究会
  • Place of Presentation: 東京
  • Year and Date: 2008-11-08
• [Presentation] 細胞内標識法を用いたミクログリアならびにアストロサイト突起の微細構造の解析 (2008)
  • Author(s): 山田純、神野尚三、中西博
  • Organizer: 第13回グリア研究会
  • Place of Presentation: 東京
  • Year and Date: 2008-11-08
• [Presentation] 破骨前駆細胞の貪食機能に着目した新たな骨破壊抑制法 (2008)
  • Author(s): 武洲、馬紅梅、中西博
  • Organizer: 第50基礎歯科医学会
  • Place of Presentation: 東京
  • Year and Date: 2008-09-25
• [Presentation] Phospathidylserine-containing liposomes ameliorates the cytokine imbalance in the ankle joints of adjuvant arthritic rats. (2008)
  • Author(s): 馬紅梅、武洲、中西博
  • Organizer: 第50基礎歯科医学会
  • Place of Presentation: 東京
  • Year and Date: 2008-09-25
• [Presentation] Inhibition of NMDA-induced outward currents by interleukin-1β in hippocampal neurons. (2008)
  • Author(s): 張馨文, 武洲, 中西博
  • Organizer: 第50基礎歯科医学会
  • Place of Presentation: 東京
  • Year and Date: 2008-09-25
• [Presentation] 中高年における慢性末梢炎症は深刻な脳炎症を引き起こす (2008)
  • Author(s): 徳田幸恵、張馨文、武洲、中西博
  • Organizer: 第50基礎歯科医学会
  • Place of Presentation: 東京
  • Year and Date: 2008-09-25
• [Presentation] Age-dependent differentiation of the barrier function of the leptomeninges in the cerebral cortex by activated glial cells during the systemic inflammation. (2008)
  • Author(s): Wu Z, Tokuda Y, Zhang XW, Nakanishi H
  • Organizer: 第26回CINP
  • Place of Presentation: ミュンヘン
  • Year and Date: 2008-07-13
• [Presentation] Involvement of extracellular nucleotides in microglial synaptic strippingresponse. (2008)
  • Author(s): 中西博
  • Organizer: 第81回日本薬理学会年会、シンポジウム「細胞外ヌクレオチドによる脳機能制御-分子ダイナミクスと疾病への関与」
  • Place of Presentation: 横浜
  • Year and Date: 2008-03-17
• [Presentation] Novel therapeutuc intervention with overexpression of TFAM against the age-dependent memory impairement. (2008)
  • Author(s): Hayshi Y, Yoshida M, Yamamto M, Ide T, Kang D, Nakanishi H
  • Organizer: 第81回日本薬理学会年会
  • Place of Presentation: 横浜
  • Year and Date: 2008-03-17
• [Book] Regulation of myeloid phagocytes by phosphatidylserine-containing liposomes : possible incolvement of prostaglandin E_2 and the potential terapeutic application.(Ed., GM Goodwin)(In : Prostaglandins : Biochemistry, Functions, Types and Roles) (2010)
  • Author(s): Wu Z, Nakanishi H.
  • Total Pages: 81-92
  • Publisher: Nova Science Publisher Inc., New York
• [Book] Cathepsin-dependent neuronal death pathways induced by methylmercury.(Ed. AP Clampet)(In : Methylmercury : Formation, Sources and Health Effects)
  • Author(s): Nakanishi H, Wu Z.
  • Publisher: Nova Science Publisher Inc., New York, in press
• [Remarks] ホームページ等 なし