Canalis Ernesto, Zanotti Stefano
Departments of Orthopaedic Surgery and Medicine, and the UConn Musculoskeletal Institute, UConn Health, Farmington, Connecticut, 06030-5456.
J Cell Biochem. 2017 Jul;118(7):1819-1826. doi: 10.1002/jcb.25859. Epub 2017 Mar 9.
Notch induces Hairy Enhancer of Split (Hes)1 and Hes-related with YRPW motif (Hey) Hey1, Hey2 and Hey-like (HeyL) expression in osteoblasts, but it is not known whether any of these target genes mediates the effect of Notch in the skeleton. We demonstrated that Notch1 activation in osteoblasts/osteocytes induces Hes1, Hey1, Hey2, and HeyL, but HeyL was induced to a greater extent than other target genes. To characterize HeyL null mice for their skeletal phenotype, microcomputed tomography (µCT) and histomorphometric analysis of HeyL null and sex-matched littermate controls was performed. µCT demonstrated modest cancellous bone osteopenia in 1 month old male mice and normal microarchitecture in 3 month old male HeyL null mice. Female HeyL null mice were not different from controls at either 1 or 3 months of age. Bone histomorphometry did not demonstrate differences between HeyL null mice of either sex and littermate controls. In conclusion, HeyL null mice do not exhibit an obvious skeletal phenotype demonstrating that HeyL is dispensable for skeletal homeostasis. J. Cell. Biochem. 118: 1819-1826, 2017. © 2016 Wiley Periodicals, Inc.
Notch可诱导成骨细胞中毛状分裂增强子（Hes）1以及含YRPW基序的Hes相关蛋白（Hey），即Hey1、Hey2和类Hey蛋白（HeyL）的表达，但尚不清楚这些靶基因中是否有任何一个介导了Notch在骨骼中的作用。我们证明，成骨细胞/骨细胞中Notch1的激活可诱导Hes1、Hey1、Hey2和HeyL的表达，但HeyL的诱导程度比其他靶基因更高。为了通过骨骼表型来表征HeyL基因敲除小鼠，我们对HeyL基因敲除小鼠及其性别匹配的同窝对照小鼠进行了显微计算机断层扫描（µCT）和组织形态计量学分析。µCT显示，1月龄雄性小鼠出现中度松质骨骨质减少，而3月龄雄性HeyL基因敲除小鼠的微观结构正常。1月龄和3月龄的雌性HeyL基因敲除小鼠与对照小鼠没有差异。骨组织形态计量学分析表明，不同性别的HeyL基因敲除小鼠与同窝对照小鼠之间没有差异。总之，HeyL基因敲除小鼠未表现出明显的骨骼表型，这表明HeyL对于骨骼稳态并非必需。《细胞生物化学杂志》118: 1819 - 1826, 2017年。© 2016威利期刊公司
