Departments of Materials and Bioengineering, and the Institute of Biomedical Engineering, Imperial College London, London, United Kingdom.
PLoS One. 2013 Nov 27;8(11):e82035. doi: 10.1371/journal.pone.0082035. eCollection 2013.
Many cartilage tissue engineering approaches aim to differentiate human mesenchymal stem cells (hMSCs) into chondrocytes and develop cartilage in vitro by targeting cell-matrix interactions. We sought to better inform the design of cartilage tissue engineering scaffolds by understanding how integrin expression changes during chondrogenic differentiation. In three models of in vitro chondrogenesis, we studied the temporal change of cartilage phenotype markers and integrin subunits during the differentiation of hMSCs. We found that transcript expression of most subunits was conserved across the chondrogenesis models, but was significantly affected by the time-course of differentiation. In particular, ITGB8 was up-regulated and its importance in chondrogenesis was further established by a knockdown of integrin β8, which resulted in a non-hyaline cartilage phenotype, with no COL2A1 expression detected. In conclusion, we performed a systematic study of the temporal changes of integrin expression during chondrogenic differentiation in multiple chondrogenesis models, and revealed a role for integrin β8 in chondrogenesis. This work enhances our understanding of the changing adhesion requirements of hMSCs during chondrogenic differentiation and underlines the importance of integrins in establishing a cartilage phenotype.
许多软骨组织工程方法旨在通过靶向细胞-基质相互作用将人骨髓间充质干细胞（hMSCs）分化为软骨细胞并在体外开发软骨。我们试图通过了解整合素表达在软骨分化过程中的变化，更好地为软骨组织工程支架的设计提供信息。在三种体外软骨发生模型中，我们研究了 hMSCs 分化过程中软骨表型标志物和整合素亚基的时间变化。我们发现，大多数亚基的转录表达在软骨发生模型中是保守的，但受分化时间进程的显著影响。特别是，ITGB8 被上调，其在软骨发生中的重要性进一步通过整合素 β8 的敲低得到证实，这导致非透明软骨表型，未检测到 COL2A1 的表达。总之，我们在多种软骨发生模型中对整合素表达在软骨发生中的时间变化进行了系统研究，并揭示了整合素 β8 在软骨发生中的作用。这项工作增强了我们对 hMSCs 在软骨发生过程中不断变化的粘附要求的理解，并强调了整合素在建立软骨表型中的重要性。
