磷脂酰丝氨酸脂质体对大鼠成骨细胞及骨生成影响的实验研究

It was well known that exposure of phosphatidylserine (PS) play a central role in the recognition and phagocytosis of apoptotic cells by phagocytes. PS containing liposomes (PSL) can mimic the effects of apoptotic cells on phagocytes. We have recently reported that PSL strongly inhibit inflammatory bone loss in adjuvant arthritic (AA) rats. This effect was considered to attribute to the inhibition of osteoclastogenesis through the secretion of prostaglandin E2 (PGE2) and transforming growth factor-b1 （TGF-b1）by osteoclast precursors and ameliorating the cytokine imbalance in the ankle joints of adjuvant arthritic rats after the phagocytosis of PSL. Both the production of receptor activator of NF-kB ligand（RANKL） and the expression of its receptor RANK（receptor activator of NF-kB） were down regulated during these processes. As another main member cell of bone remodeling, osteoblast plays an important role in regulating osteoclastogenesis and maintaining the function of osteoclasts. At the same time, our latest datas have shown that Class scavenger receptor type I (SR-BI), which was considered to be a receptor that can bind to PS directly, also expresses on the surface of rat calvaria osteoblasts. This makes us wandering whether PSL can directly affect the proliferation or differentiation of osteoblasts and consequently promote bone formation. In present study, to overall demonstrate the role of PSL on bone remodeling, we are trying to detect the effects of PSL on osteoblasts by using rat calvaria osteoblasts and a bone formation model. In vitro, PSL will be applied to the cell culture system of rat calvaria osteoblasts and the change of osteoblast proliferation, differentiation and bone nodules formation will be detected. Different signal molecule inhibitors will be used to detect the signal path way by which PSL affect rat calvaria osteoblasts. In vivo, the rat incisor was extracted to establish a bone formation model, by which the bone formation of the tooth socket after the tooth extraction will be detected with or without the effect of PSL. Together with the previous reports, the results of this study will provide us a new thought and a scientific base of the therapies for bone destruction diseases.

磷脂酰丝氨酸（PS）外露在吞噬细胞识别和吞噬凋亡细胞过程中起着重要的作用。含有PS的脂质体（PSL）能够模拟凋亡细胞的这一效应而被吞噬细胞识别、吞噬并参与免疫调节。最近我们报道了，PSL能够抑制破骨细胞分化，抑制大鼠关节炎引起的关节骨破坏。我们最新的研究结果显示，在大鼠颅骨来源的成骨细胞的表面也有PS相关的受体的表达。由此我们设想PSL很有可能对成骨细胞也具有一定的调节作用。本研究中，我们希望通过对颅骨来源的成骨细胞的研究，检测PSL对成骨细胞的增殖，分化和功能的影响，并通过信号分子抑制剂对产生这一影响所经过的信号通路进行检测；同时利用拔牙大鼠动物模型检测PSL对大鼠拔牙窝内新骨生成的影响。结合以往的研究成果，本项目的结果，将全面地揭示PSL对骨重建的作用，从而为临床上骨破坏性疾病的治疗提供一个新的思路和科学依据。

磷脂酰丝氨酸脂质体（phosphatidylserine-containing liposome PSL）能够通过促进破骨细胞前驱细胞分泌TGF- 1和PGE2，下调RANK和RANKL的表达，从而抑制破骨细胞分化；同时PSL通过调节关节内浸润巨噬细胞释放抗/促炎因子的平衡，下调RANK和RANKL的表达，而抑制大鼠药物性关节炎引起的关节骨破坏。同时，TGF- 1是促进成骨细胞增殖分化和骨再生的重要因子，而成骨细胞对RANK及RANKL的表达具有重要的调节作用。那么PSL是否可能通过直接促进成骨细胞功能而促进骨再生呢？本研究中，通过对大鼠颅骨来源的成骨细胞及大鼠拔牙后牙槽窝内骨再生的研究，检测PSL对成骨细胞的调节作用，全面揭示了PSL对骨重建的影响，为临床上寻找骨破坏性疾病的治疗方法提供新的思路和科学依据。