Department of Biochemistry and Molecular Biology, Nihon University School of Dentistry at Matsudo, Chiba 271-8587, Japan.
J Biomed Mater Res B Appl Biomater. 2013 Jul;101(5):804-12. doi: 10.1002/jbm.b.32884. Epub 2013 Feb 9.
Caveolin is an essential and signature protein of caveolae. Caveolin-1 participates in signal transduction processes by acting as a scaffolding protein that concentrates, organizes and functional regulates signalling molecules within caveolar membranes. Beta-tricalcium phosphate (β-TCP) has been widely used for scaffold in tissue engineering due to its high biodegradability, osteoconductivity, easy manipulation, and lack of histotoxicity. To better understand the role of caveolin-1 in bone homeostasis and response to β-TCP scaffold, β-TCP was implanted into the dog mandible defects in beagle dogs, and gene expression profiles were examined focused on the molecular components involved in caveolin-1 regulation. Here we showed the quantitative imageology analysis characterized using in vivo micro-computed tomography (CT) images at 4 and 7 days after β-TCP implanted in dog mandibles. The bone reformation by using the β-TCP scaffolds began within 4 days of surgery, and was healing well at 7 days after surgery. Higher mRNA level of caveolin-1 was observed in β-TCP-implanted Beagle dog mandibles compared with controls at day 4 and day 7 post-surgery. The enhancement of caveolin-1 by β-TCP was further confirmed by immunohistochemistry and immunofluorescence analysis. We further revealed increased Smad7 and Phospho Stat3 expression in β-TCP-implanted specimens. Taken together, these results suggest that the enhancement of caveolin-1 play an important role in accelerating bone formation by β-TCP.
窖蛋白是质膜窖的标志性和必需蛋白。窖蛋白-1 作为一种支架蛋白,通过浓缩、组织和功能调节窖膜中的信号分子参与信号转导过程。β-磷酸三钙(β-TCP)由于其高生物降解性、骨传导性、易于操作和缺乏组织毒性而被广泛用于组织工程支架。为了更好地了解窖蛋白-1 在骨稳态和对β-TCP 支架的反应中的作用,将β-TCP 植入比格犬下颌骨缺损中,并对涉及窖蛋白-1 调节的分子成分的基因表达谱进行了检测。在这里,我们展示了在犬下颌骨植入β-TCP 后 4 天和 7 天使用体内微计算机断层扫描(CT)图像进行的定量影像学分析。β-TCP 支架的骨形成在手术后 4 天内开始,手术后 7 天愈合良好。与手术后 4 天和 7 天的对照组相比,β-TCP 植入的比格犬下颌骨中窖蛋白-1 的 mRNA 水平更高。免疫组织化学和免疫荧光分析进一步证实了 β-TCP 对窖蛋白-1 的增强作用。我们还发现β-TCP 植入标本中 Smad7 和磷酸化 Stat3 的表达增加。综上所述,这些结果表明,β-TCP 增强窖蛋白-1 的表达在加速骨形成中起重要作用。