Effects of arachidonic acid metabolites on the bone metabolism

从小鼠颅骨分离的培养成骨细胞样细胞（MC 3 T3-E1）已被确认保留其独特的启动矿化的特性。因此，该细胞已被用作体外研究骨形成的良好模型。由于3 T3-E1细胞具有较高的前列腺素E_2（PGE_2）合成能力，我们研究了PGE_2对成骨细胞表型的影响。在培养早期，消炎痛抑制细胞增殖，而PGE_2则促进细胞增殖，在培养后期，细胞向骨细胞分化并矿化。PGE_2的合成较早期下降了10%。如果PGE_2的合成被吲哚美辛阻断，则矿物质存款的出现被刺激。其次，我们利用小鼠骨髓培养系统研究了PGE_2对破骨细胞样细胞形成的影响。PGE_2可促进多核破骨细胞的形成。认为PGE_2的刺激部位是在PGE_2分步处理中促进单核细胞向抗酒石酸酸性磷酸酶染色细胞的分化。众所周知，PGE_2是一种强有力的骨吸收因子，但也有报道称PGE_2可诱导破骨细胞收缩，从而抑制骨吸收。在我们的实验中，我们证明了由成骨细胞产生的PGE_2刺激破骨细胞的增殖和募集。而在骨补充的最后阶段，PGE_2对矿化和骨吸收均有抑制作用，提示PGE_2在骨代谢中起重要作用。

Cultured osteoblast-like cells (MC3T3-E1) isolated from mouse calvaria have been recognized to retain their unique properties of initiating mineralization. Therefore, the cells have been used as a good model for studing bone formation in vitro. Since 3T3-E1 cells have a high capacity for prostaglandin E_2 (PGE_2) synthesis, we studied the effects of PGE_2 on the phenotype of osteoblasts. in the early stage of culture, indomethacin suppressed the proliferation and an addition of PGE_2 stimultes it. In the lasts stage of the culture, the cells were differentiated to osteocytes and mineralized. In this stage, PGE_2 synthesis was down to 10% compared with that in the early stage. If the PGE_2 synthesis was blocked by indomethacin, the appearance of the mineral deposit was stimulated. On the contrary, the addition of PGE_2 suppressed the mineralization completely.Next, we examined the effect of PGE_2 on osteoclast-like cell formation using mouse bone marrow culture system. PGE_2 stimulated the formation of multi-nucleated osteoclasts in this system. The site of the stimulation by PGE_2 is thought to be promoting the differentiation from monocytes to tartrate-resistant acid phosphatase stained cells in the step-wise treatment of PGE_2. It is well-known that PGE_2 is a potent bone resobing factor, while there are reports that PGE_2 induced contraction in isolated osteoclasts, resulting in suppression of bone resorption. In our experiment, we demonstrate that PGE_2 produced by osteoblasts stimulated both proliferation and the recruitment of osteoclasts. however, in the last stage of bone recruitment PGE_2 inhibited both mineralization and bone resorption.These data suggest that PGE_2 is the very important autacoid in bone metabolism.