Extracellular matrix synthesis and degradation in functionally distinct tendons.
Doctoral thesis, UCL (University College London).
Tendon injury is common in humans and horses, and incidence increases with age. The high-strain energy storing equine superficial digital flexor (SDFT) is injured more frequently than the low-strain positional common digital extensor (CDET). However, previous work indicated that matrix turnover is greater in the CDET than in the SDFT. It was hypothesised that matrix turnover is programmed by the cells’ strain environment; therefore high-strain energy storing tendons would have a lower rate of matrix turnover than low-strain positional tendons and the rate of matrix turnover would decrease with increasing age. The rate of matrix turnover was investigated by measuring the potential of the cells to synthesise and degrade matrix proteins, measuring the half-life of the collagenous and non-collagenous matrix proteins and assessing collagen turnover at the protein level. In vitro cell phenotype was also assessed in 2D and 3D culture and the effect of load on cells within native tissue was determined. The results show that turnover of collagenous and non-collagenous matrix proteins is differentially regulated in the functionally distinct SDFT and CDET. CDET tenocytes show greater potential for collagen turnover, whereas SDFT tenocytes have a greater potential for proteoglycan turnover; differences that are also present at the protein level. The differences in cell phenotype identified in vivo were lost in 2D and 3D culture, but tendon organ culture resulted in the maintenance of tenocyte phenotype. The cells’ ability to turnover the matrix does not decrease with increasing age, but collagen within the SDFT appears to become more resistant to degradation with ageing. This results in the accumulation of partially degraded collagen within the SDFT which may have a detrimental effect on tendon mechanical properties. These findings will help to elucidate the mechanisms behind the development of age-related tendinopathy and will be of use when developing treatment regimes.
|Title:||Extracellular matrix synthesis and degradation in functionally distinct tendons|
|Open access status:||An open access version is available from UCL Discovery|
|UCL classification:||UCL > School of Life and Medical Sciences > Faculty of Medical Sciences > Surgery and Interventional Science (Division of) > Institute of Orthopaedics and Musculoskeletal Science|
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