四环素-哌嗪雌酚酮上调骺板c-fos,c-jun的mRNA及其表达产物水平

EFFECTS OF 2-(3- ESTRONE-n- ETHYL-PIPERAZINE METHYL) TETRACYCLINE ON THE LEVELS OF C-FOS AND C-JUN mRNAs AND THEIR PRODUCT PROTEINS IN EPIPHYSEAL PLATE

目的 :研究四环素 哌嗪雌酚酮 (XW 6 30 )对软骨细胞c fos和c jun基因的mRNA及其表达产物水平的影响 ,初步探讨其对骨的作用机制。方法 :用原位杂交法 ,测定体外培养小鼠胚胎长骨骺板c fos和c junmRNA的水平 ,同时用免疫组织化学法 ,测定了相应的表达产物。结果 :1 0 - 7mol·L- 1XW 6 30可显著上调骺板静止区、增殖区和肥大区c fos和c jun的mRNA及其表达产物水平 ,且其作用比雌酚酮强。 结论 :XW 6 30可能通过上调软骨细胞c fos ,c jun的表达 ,促进软骨细胞中含有AP 1位点的、与骨生长发育有关的基因表达 。

AIM: 2 (3 Estrone N ethyl piperazine methyl) tetracycline(XW630) is a novel bone targeted estrogen which shows stronger action in enhancing bone formation than estrone on ovaritectomized rats while shows weaker estrogen like activity on mouse uterus. Therefore, it may be a potential compound for prevention and treatment of postmenopausal osteoporosis. The effects of XW630 on the levels of c fos and c jun mRNAs and their product proteins in long bone were studied for insight into the mechanism by which XW630 acts on bone. METHODS: The long bones of fetal mice of 16 days old were cultured in BGJb medium and treated with 10 -7 mol·L -1 XW630 or 10 -7 mol·L -1 estrone. After cultured for 48 h, the levels of mRNAs of c fos and c jun were determined by approach of in situ hybridization. Immunohistochemical analysis of c fos protein and c jun protein were also performed. RESULTS: The levels of c fos mRNA, c jun mRNA and their proteins in resting zone, proliferative zone and hypertrophic zone were all upregulated. XW630 showed stronger effects on epiphyseal plate than estrone. CONCLUSION: The results suggest the possibility that XW630 enhanced endochondral bone development by upregulating the expression of c fos and c jun in epiphyseal plate. Their proteins may in turn rapidly regulate expressions of other genes that relate to bone growth and in which there are AP 1 sites.