糖皮质激素促间充质干细胞的成骨效应

背景：糖皮质激素是有效的免疫抑制和抗炎症药物而广泛应用于临床,然而长期服用后也会引起一些不良反应如骨质疏松症。糖皮质激素通过促进成骨细胞与骨细胞的凋亡,同时抑制间充质干细胞向成骨细胞分化,导致成骨细胞数量减少;然而在一定的条件下,糖皮质激素又能够促进间充质干细胞表达成骨细胞标志基因诱导其向成骨方向分化。 目的：对以地塞米松为代表的糖皮质激素在间充质干细胞成骨分化中发挥的作用以及可能的分子机制进行综述。 方法：由第一作者检索PubMed数据库1978至2012年有关地塞米松和间充质干细胞成骨分化的文献,英文关键词“Mesenchymal stem cell,dexamethasone,osteogenesis,osteoporosis,Runx2,BMP,Noggin,GILZ,glucocorticoid receptor”以不同的组合方式查找,排除重复性的研究,最终保留55篇进行归纳综述。 结果与结论：地塞米松能够调节Runx2,Noggin以及亮氨酸拉链蛋白等基因调控间充质干细胞成骨分化。当糖皮质激素作用于间充质干细胞时,可能由糖皮质激素受体介导其生理作用,也可能在糖皮质激素与其受体结合之前就受到11β-羟甾类脱氢酶的调节。另外,生理剂量(10^-8 mol/L)的地塞米松能促进间充质干细胞成骨分化,药理剂量(≥10^-7 mol/L)有抑制作用。

Glucocorticoids promote osteogenic differentiation of mesenchymal stem cells

BACKGROUND:Glucocorticoids are immunosuppressive and anti-inflammatory drugs which are widely used in the clinic. However, long-term use of these drugs may cause several side effects, such as osteoporosis. It has been demonstrated that glucocorticoids promote the apoptosis of osteoblasts and osteocytes, and thus inhibit the differentiation of mesenchymal stem cells into osteoblasts, resulting in a decrease number of osteoblasts. However, glucocorticoids can stimulate osteogenic differentiation of mesenchymal stem cells by enhancing the expression of osteoblastic markers under appropriate induction conditions. OBJECTIVE:To review the effect of dexamethasone on the osteogenic differentiation of mesenchymal stem cells and the possible molecular mechanism. METHODS:The PubMed database was retrieved for articles regarding dexamethasone and osteogenic differentiation of mesenchymal stem cells published from 1978 to 2012. The English key words were “mesenchymal stem cell, dexamethasone, osteogenesis, osteoporosis, Runx2, BMP, Noggin, GILZ, glucocorticoid receptor”. A total of 55 articles were suitable for final analysis after repetitive articles were excluded. RESULTS AND CONCLUSION:Dexamethasone controls the osteogenic differentiation of mesenchymal stem cells by regulating the expression of Runx2, Noggin and glucocorticoid-induced leucine zipper. Glucocorticoid receptor may mediate the effect of glucocorticoids, or 11β-hydroxysteroid dehydrogenase interconverts the activity of glucocorticoids before it binds to glucocorticoid receptor. In addition, glucocorticoids can promote the osteogenic differentiation of mesenchymal stem cells at a physiological dose of 10^-8 mol/L while it inhibits the osteogenic differentiation at a pharmacological dose of ≥10^-7 mol/L.