کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
2108041 | 1083718 | 2008 | 12 صفحه PDF | دانلود رایگان |
![عکس صفحه اول مقاله: Transient Inhibition of the Hedgehog Pathway in Young Mice Causes Permanent Defects in Bone Structure Transient Inhibition of the Hedgehog Pathway in Young Mice Causes Permanent Defects in Bone Structure](/preview/png/2108041.png)
SummaryThe Hedgehog (Hh) pathway plays critical roles in normal development and in tumorigenesis. We generated Gli-luciferase transgenic mice to evaluate the Smo inhibitor, HhAntag, by whole animal functional imaging. HhAntag rapidly reduced systemic luciferase activity in 10- to 14-day-old mice following oral dosing. Although pathway activity was restored 2 days after drug removal, brief inhibition caused permanent defects in bone growth. HhAntag inhibited proliferation and promoted differentiation of chondrocytes, leading to dramatic expansion of the hypertrophic zone. After drug removal, osteoblasts invaded the cartilage plate, mineralization occurred, and there was premature fusion of the growth plate resulting in permanent disruption of bone epiphyses.
Journal: - Volume 13, Issue 3, 11 March 2008, Pages 249–260