丙二醛通过激活p38和JNK通路抑制间充质干细胞成骨分化

为了探索丙二醛（malonaldehyde, MDA）抑制间充质干细胞（mesenchymal stem cells，MSCs）成骨分化的作用机制，用不同浓度的丙二醛孵育MSCs，进行成骨诱导培养，检测碱性磷酸酶活性和钙结节形成|并检测p38和JNK表达水平和磷酸化程度，用这两种信号分子的特异性阻断剂进行验证. 结果发现，丙二醛浓度依赖性地降低MSCs碱性磷酸酶的活性,抑制钙结节的形成|并引起p38和JNK的表达上调和磷酸化增强，诱导JNK由胞浆向胞核转位| p38和JNK阻断剂对丙二醛的上述效应有拮抗作用. 结果表明，丙二醛可抑制MSCs的成骨诱导分化，其作用机制涉及p38和JNK信号通路的参与.

Malonaldehyde Suppresses Osteogenic Differentiation of Mesenchymal Stem Cells by Activating p38 and JNK

This study was to explore the effects of malonaldehyde (MDA) on the osteogenic differentiation of mesenchymal stem cells (MSCs) and the related signaling. The activity of alkaline phosphatase and the formation of mineralized nodule were examined after osteogenic differentiations of MSCs with or without pretreatment of MDA in vitro. Furthermore, the p38 and JNK expression and phosphorylation were measured following MDA pretreatment with and without the addition of p38 MAPK inhibitor or JNK inhibitors. The results showed that MDA treatments induced a concentration dependent suppression of alkaline phosphatase activity, as well as the formation of mineralized nodule, with the increase of the expression and phosphorylation of both p38 and JNK, and translocation of JNK from the cytoplasm to the nucleus. Specific inhibitors of p38 and JNK antagonized MDA in MSC osteogenic differentiations. These findings indicated that malonaldehyde suppressed osteogenic differentiation of MSCs involving the suppression of p38 and JNK signaling pathways.