Abstract
The tendon-bone interface (enthesis) is a highly sophisticated biomaterial junction that allows stress transfer between mechanically dissimilar materials. The enthesis encounters very high mechanical demands and the regenerative capacity is very low resulting in high rupture recurrence rates after surgery. Tissue engineering offers the potential to recover the functional integrity of entheses. However, recent enthesis tissue engineering approaches have been limited by the lack of knowledge about the cells present at this interface. Here we investigated the cellular differentiation of enthesis cells and compared the cellular pattern of enthesis cells to tendon and cartilage cells in a next generation sequencing transcriptome study. We integrated the transcriptome data with proteome data of a previous study to identify biomarkers of enthesis cell differentiation. Transcriptomics detected 34468 transcripts in total in enthesis, tendon, and cartilage. Transcriptome comparisons revealed 3980 differentially regulated candidates for enthesis and tendon, 395 for enthesis and cartilage, and 946 for cartilage and tendon. An asymmetric distribution of enriched genes was observed in enthesis and cartilage transcriptome comparison suggesting that enthesis cells are more chondrocyte-like than tenocyte-like. Integrative analysis of transcriptome and proteome data identified ten enthesis biomarkers and six tendon biomarkers. The observed gene expression characteristics and differentiation markers shed light into the nature of the cells present at the enthesis. The presented markers will foster enthesis tissue engineering approaches by setting a bench-mark for differentiation of seeded cells towards a physiologically relevant phenotype.
Highlights
Interfaces between mechanically dissimilar materials are prone to stress concentrations and the failure risk is increased
Tissue engineering is a promising and evolving field to tackle the challenge of tissue interface regeneration
Most strategies of tissue engineering involve the use of scaffolds of any sort in combination with cells to biomimic the physiological behavior of the respective tissue
Summary
Interfaces between mechanically dissimilar materials are prone to stress concentrations and the failure risk is increased. Entheses are hard-soft interfaces between tendon/ligament and bone and are subject to extraordinary high mechanical demands. Surgical reconstruction of entheses is very challenging and the regenerative capacity of these biological hard-soft interfaces is low. Wound healing at the interface region mostly results in tissue with lower.
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