Indiana Center for Musculoskeletal Health, Department of Anatomy, Cell Biology and Physiology, School of Medicine, Indiana University, Indianapolis, IN 46202, United States of America.
Indiana Center for Musculoskeletal Health, Department of Anatomy, Cell Biology and Physiology, School of Medicine, Indiana University, Indianapolis, IN 46202, United States of America.
Bone. 2023 May;170:116724. doi: 10.1016/j.bone.2023.116724. Epub 2023 Mar 1.
Although osteoblasts and osteocytes are descended from the same lineage, they each have unique and essential roles in bone. Targeting gene deletion to osteoblasts and osteocytes using the Cre/loxP system has greatly increased our current understanding of how these cells function. Additionally, the use of the Cre/loxP system in conjunction with cell-specific reporters has enabled lineage tracing of these bone cells both in vivo and ex vivo. However, concerns have been raised regarding the specificity of the promoters used and the resulting off-target effects on cells within and outside of the bone. In this review, we have summarized the main mouse models that have been used to determine the functions of specific genes in osteoblasts and osteocytes. We discuss the expression patterns and specificity of the different promoter fragments during osteoblast to osteocyte differentiation in vivo. We also highlight how their expression in non-skeletal tissues may complicate the interpretation of study results. A thorough understanding of when and where these promoters are activated will enable improved study design and greater confidence in data interpretation.
虽然成骨细胞和骨细胞来自同一谱系，但它们在骨骼中各自具有独特且必不可少的作用。使用 Cre/loxP 系统对成骨细胞和骨细胞进行靶向基因缺失，极大地提高了我们目前对这些细胞功能的理解。此外，使用 Cre/loxP 系统结合细胞特异性报告基因，使得这些骨细胞在体内和体外都能够进行谱系追踪。然而，人们对所使用的启动子的特异性以及对骨骼内外细胞的潜在脱靶效应表示担忧。在这篇综述中，我们总结了主要的小鼠模型，这些模型被用来确定特定基因在成骨细胞和骨细胞中的功能。我们讨论了不同启动子片段在体内成骨细胞向骨细胞分化过程中的表达模式和特异性。我们还强调了它们在非骨骼组织中的表达如何使研究结果的解释复杂化。对这些启动子何时何地被激活有一个透彻的了解，将能够改进研究设计，并使数据解释更有信心。
