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

基于吞噬细胞功能调节的含磷脂酰丝氨酸脂质体抑制骨破坏

• 批准号: 20390472
• 负责人: HIROSHI Nakanishi
• 金额: $ 12.4万
• 依托单位: Kyushu University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2008
• 资助国家: 日本
• 起止时间: 2008 至 2010
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-20390472/
• 关键词: 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; 炎症生骨吸収; アルカリフォスファターゼ; リン質リポソーム; アジュバント関節炎; プロスタグランジンE2; TGF-β1; RANKL; ICAM-1; CD44

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.

这项研究研究了含磷脂酰丝氨酸的脂质体（PSL）对破骨细胞生成的影响。在大鼠骨髓培养系统中，破骨细胞前体将PSL吞噬了秘密的TGF-β1和PGE2，这又通过NF-κB配体的下调受体激活剂的下调抑制了破骨细胞生成，NF-κB配体，NF-κB的受体激活剂。与这些体外观察一致，I.M。 PSL的注射显着提高了TGF-β1和PGE2的血浆水平，并降低了NF-κB配体的受体激活剂的表达，NF-κB配体是NF-κB的受体激活剂，NF-κB的受体激活剂具有可调节性关节炎的大鼠的骨骼关节。加上对破骨细胞基因的抑制作用，PSL参与了骨重塑的调节。由于PS是细胞膜的组成部分，因此PSL可以是针对异常骨质流失的潜在有效的药物干预，例如骨质疏松症而没有有害的副作用。

项目成果

Acute p38-mediated inhibition of NMDA-induced outward currents in hippocampal CA1 neurons by interleukin-1β

• DOI: 10.1016/j.nbd.2009.12.028
• 发表时间: 2010-04-01
• 期刊: NEUROBIOLOGY OF DISEASE
• 影响因子: 6.1
• 作者: Zhang, Ruoyu;Sun, Li;Nakanishi, Hiroshi
• 通讯作者: Nakanishi, Hiroshi

Differebtial inolvement of astrocytes and microglia in neuronal survival after hypoglossal nerve injury.

舌下神经损伤后星形胶质细胞和小胶质细胞在神经元存活中的差异参与。

• 发表时间: 2010
• 作者: Yamada J;Jinno S;Nakanishi H
• 通讯作者: Nakanishi H

Inhibition of NMDA-induced outward currents by interleukin-1β in hippocampal neurons. Biochem.

Biochem 抑制海马神经元中白细胞介素 1β 诱导的外向电流。

• 发表时间: 2008
• 期刊: Biophys.Res.Commun. 372
• 作者: Zhang R;Yamada J;Hayashi Y;Wu Z;Koyama S;Nakanishi H.
• 通讯作者: Nakanishi H.

Possible involvement of cathepsin B released by microglia in methylmercury-induced cerebellar pathological changes in the adult rats.

小胶质细胞释放的组织蛋白酶 B 可能参与甲基汞诱导的成年大鼠小脑病理变化。

• 发表时间: 2008
• 期刊: Neurosci. Lett. 442
• 作者: Sakamoto M.;et al.
• 通讯作者: et al.

Involvement of cathepsin B in the processing and secretion of interleukin-1b in c chromogranin A-stimulated microglia

组织蛋白酶 B 参与 c 嗜铬粒蛋白 A 刺激的小胶质细胞中白细胞介素 1b 的加工和分泌

• 发表时间: 2010
• 期刊: Glia
• 影响因子: 6.2
• 作者: Terada;et al.
• 通讯作者: et al.