Abstract
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.
Highlights
Articular hyaline cartilage has a low capacity for self-repair following traumatic injury or degeneration from osteoarthritis, a disease associated with the increasingly ageing population
While the 21 day time-course was not long enough to produce mature cartilage, the trends of the integrin transcript expression we measured in differentiating human mesenchymal stem cells (hMSCs) were in agreement with the expression we found in cells derived from healthy human articular cartilage
We found that integrin expression generally decreased in chondrogenic differentiation and that the expression of most subunits was temporally regulated
Summary
Articular hyaline cartilage has a low capacity for self-repair following traumatic injury or degeneration from osteoarthritis, a disease associated with the increasingly ageing population. The extent of endogenous repair is related to the size of the defect and is limited by the avascular nature of cartilage and the low mitotic activity of chondrocytes. A wide range of tissue engineering strategies have been employed but the paradigm for most involves the combination of cells, a scaffold, and soluble or insoluble cues, many iterations of which have been studied [2]. There have been a number of successful engineering approaches, mimicking many of the native properties of cartilage, in the hope that the cell phenotype will respond . Embryogenesis remains the only reliable means of generating native cartilage, and the best option available to surgeons is a selection of polymer fleeces, sponges, and fibrous materials seeded with the patient’s own stem cells for implantation into the defect site
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