成骨细胞
糖皮质激素受体
内分泌学
糖皮质激素
内科学
碱性磷酸酶
受体
骨质疏松症
生物
化学
细胞生物学
酶
医学
生物化学
体外
作者
Lin Wu,Hanmei Qi,Yi Zhong,Lianyou Shan,Jing Yu,Juan Liu,Long Wang,Jianhua Bi,Guoxian Ding,Wenjuan Di,Juanmin Zha,Feng Liu,Guoxian Ding
标识
DOI:10.1507/endocrj.ej12-0376
摘要
Pharmacologic glucocorticoids (GCs) inhibit osteoblast function and induce osteoporosis. 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) may play a role in osteoporosis as it regulates GC action at a pre-receptor level by converting inactive GC to its active form. Further, 11β-HSD1 was found increasingly expressed in bone with age. In spite of these observations, its function in senile osteoporosis remains uncertain. In this study we constructed a lentiviral vector overexpressing mouse 11β-HSD1 and then MC3T3-E1 preosteoblast cells were infected by the negative control lentivirus and 11β-HSD1-overexpressing lentivirus, respectively. The mRNA and protein levels of 11β-HSD1 were significantly increased in MC3T3-E1 cells that were infected by 11β-HSD1-overexpressing lentivirus compared to the cells infected by the negative control lentivirus. The osteogenic differentiation of MC3T3-E1 preosteoblast cells was dramatically suppressed by 11β-HSD1 overexpression under the reductase substrate dehydrocorticosterone (DHC). The inhibition effect was similar to the inhibition of osteogenesis by over-dose GCs, including ALP activity, the ultimate calcium nodus formation as well as the expression of the osteogenic genes such as ALP, BSP, OPN and OCN. However, with addition of BVT.2733, a selective inhibitor of 11β-HSD1, all of the above osteogenic repression effects by 11β-HSD1 overexpression were reversed. Furthermore, a GC receptor antagonist RU486 also showed the similar effect, preventing inhibition of osteogenesis by 11β-HSD1 overexpression. These results demonstrated that the specific 11β-HSD1 inhibitor BVT.2733 can reverse the suppression effect towards osteogenic differentiation in 11β-HSD1 overexpressed MC3T3-E1 cells. Inhibition of 11β-HSD1 can be a new therapeutic strategy for senile osteoporosis.
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