Phosphatidylserine-Containing Liposomes Inhibit the Differentiation of Osteoclasts and Trabecular Bone Loss
Phosphatidylserine-Containing Liposomes Inhibit the Differentiation of Osteoclasts and Trabecular Bone Loss
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DOI：
10.4049/jimmunol.0803609
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发表时间：
2010-03
期刊：
影响因子：
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通讯作者：
Zhou Wu;Hong-Mei Ma;T. Kukita;Y. Nakanishi;H. Nakanishi
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文献类型：
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作者：
Zhou Wu;Hong-Mei Ma;T. Kukita;Y. Nakanishi;H. Nakanishi
含有磷脂酰丝氨酸（PS）的脂质体被包括巨噬细胞、小胶质细胞和树突细胞的吞噬细胞吞噬。PS脂质体（PSLs）模拟凋亡细胞对这些吞噬细胞的作用，以诱导抗炎分子的分泌并抑制树突状细胞的成熟。然而，PSL对破骨细胞（也与普通骨髓前体细胞不同）的影响仍有待确定。本研究探讨了PSLs对破骨细胞生成的影响。在大鼠骨髓培养体系中，破骨细胞前体吞噬PSL分泌TGF-β1和PGE 2，反过来通过下调NF-κB配体受体激活剂、NF-κB受体激活剂、ICAM-1和CD 44抑制破骨细胞的生成。与这些体外观察结果一致，i.m. PSLs可显著升高佐剂性关节炎大鼠踝关节骨组织中TGF-β1和PGE 2的水平，降低NF-κB配体受体激活剂、NF-κB受体激活剂和ICAM-1的表达。使用显微计算机断层扫描的定量分析显示，PSLs以及TGF-β1与PGE 2一起显著抑制AA诱导的松质骨丢失。这些观察结果强烈表明，PSL产生TGF-β1和PGE 2释放，导致抑制破骨细胞生成和AA诱导的小梁骨丢失。由于PS是细胞膜的组分，因此PSLs可以是针对异常骨丢失（例如骨质疏松症）的潜在有效的药理学干预，而没有有害的副作用。
Liposomes containing phosphatidylserine (PS) are engulfed by phagocytes including macrophages, microglia, and dendritic cells. PS liposomes (PSLs) mimic the effects of apoptotic cells on these phagocytes to induce the secretion of anti-inflammatory molecules and to inhibit the maturation of dendritic cells. However, the effects of PSLs on osteoclasts, which are also differentiated from the common myeloid precursors, remain to be determined. This study investigated the effects of PSLs on the osteoclastogenesis. In the rat bone marrow culture system, osteoclast precursors phagocytosed PSLs to secrete TGF-β1 and PGE2, which in turn inhibited osteoclastogenesis through the downregulation of receptor activator for NF-κB ligand, receptor activator of NF-κB, ICAM-1, and CD44. 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, and ICAM-1 in the skeletal tissues of ankle joints of rats with adjuvant arthritis (AA). A quantitative analysis using microcomputed tomography revealed that PSLs as well as TGF-β1 together with PGE2 significantly inhibited AA-induced trabecular bone loss. These observations strongly suggest that PSLs generate TGF-β1 and PGE2 release, leading to inhibit osteoclastogenesis and AA-induced trabecular bone loss. 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.