Department of Biomedical Engineering, Columbia University, New York, NY, USA.
Department of Medicine, Columbia University, New York, NY, USA.
J Tissue Eng Regen Med. 2018 Feb;12(2):468-478. doi: 10.1002/term.2500. Epub 2017 Oct 6.
Subcutaneous implantation in a mouse can be used to investigate tissue maturation in vivo. Here we demonstrate that this simple model can recapitulate endochondral ossification associated with native skeletal development. By histological and micro-computed tomography analysis we investigated morphological changes of immature bovine osteochondral tissues over the course of subcutaneous implantation in immunocompromised mice for up to 10 weeks. We observed multiple similarities between the ectopic process and native endochondral ossification: (i) permanent cartilage retention in the upper zones; (ii) progressive loss of transient cartilage accompanied by bone formation at the interface; and (iii) remodelling of nascent endochondral bone into mature cancellous bone. Importantly, these processes were mediated by osteoclastogenesis and vascularization. Taken together, these findings advance our understanding of how the simple ectopic model can be used to study phenotypic changes associated with endochondral ossification of native and engineered osteochondral tissues in vivo.
皮下植入小鼠体内可用于研究组织的体内成熟。在这里，我们证明了这种简单的模型可以重现与天然骨骼发育相关的软骨内骨化。通过组织学和微计算机断层扫描分析，我们研究了在免疫功能低下的小鼠皮下植入长达 10 周期间，不成熟的牛骺软骨组织的形态变化。我们观察到异位过程与天然软骨内骨化之间存在多个相似之处：（i）在上区永久保留软骨；（ii）随着界面处骨形成，瞬态软骨逐渐消失；（iii）新生软骨内骨向成熟松质骨重塑。重要的是，这些过程是由破骨细胞生成和血管生成介导的。总之，这些发现增进了我们对异位模型如何用于研究天然和工程化骺软骨组织软骨内骨化相关表型变化的理解。
