Effects of arachidonic acid metabolites on the bone metabolism

从小鼠颅骨中分离的成骨细胞样细胞（MC3T3-E1）已被认为保留了其启动矿化的独特特性。因此，这些细胞已被用作体外研究骨形成的良好模型。由于3T3-E1细胞具有较高的前列腺素e2 （PGE_2）合成能力，我们研究了PGE_2对成骨细胞表型的影响。在培养初期，吲哚美辛抑制了细胞的增殖，PGE_2的加入促进了细胞的增殖。在培养的最后阶段，细胞分化为骨细胞并矿化。在此阶段，PGE_2的合成比前期下降了10%。如果吲哚美辛阻断PGE_2的合成，则刺激矿床的出现。相反，PGE_2的加入完全抑制了成矿作用。接下来，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刺激了多核破骨细胞的形成。PGE_2刺激的部位被认为在PGE_2的分步处理中促进了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是一种有效的骨吸收因子，但有报道称PGE_2可诱导离体破骨细胞收缩，从而抑制骨吸收。在我们的实验中，我们证明了成骨细胞产生的PGE_2刺激了破骨细胞的增殖和招募。然而，在骨重建的最后阶段，PGE_2抑制矿化和骨吸收。提示PGE_2在骨代谢中起着重要的作用。

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.