Abstract
Maintenance of connective tissue integrity is fundamental to sustain function, requiring protein turnover to repair damaged tissue. However, connective tissue proteome dynamics remain largely undefined, as do differences in turnover rates of individual proteins in the collagen and glycoprotein phases of connective tissue extracellular matrix (ECM). Here, we investigate proteome dynamics in the collagen and glycoprotein phases of connective tissues by exploiting the spatially distinct fascicular (collagen-rich) and interfascicular (glycoprotein-rich) ECM phases of tendon. Using isotope labelling, mass spectrometry and bioinformatics, we calculate turnover rates of individual proteins within rat Achilles tendon and its ECM phases. Our results demonstrate complex proteome dynamics in tendon, with ~1000 fold differences in protein turnover rates, and overall faster protein turnover within the glycoprotein-rich interfascicular matrix compared to the collagen-rich fascicular matrix. These data provide insights into the complexity of proteome dynamics in tendon, likely required to maintain tissue homeostasis.
Highlights
Maintaining the structural and mechanical integrity of tissues in the musculoskeletal system, and other connective tissues, is fundamental to sustain tissue homeostasis and healthy function, requiring protein synthesis and degradation to repair and/or replace damaged tissue before damage accumulates and leads to injury (Humphrey et al, 2014)
These, and other studies, have shown greater expression of markers of extracellular matrix (ECM) degradation, as well as increased neo-peptide levels, a proxy measure of protein turnover, within the interfascicular matrix (IFM) (Spiesz et al, 2015, Thorpe et al, 2015a, Thorpe et al, 2016b), suggesting this region is more prone to microdamage, likely due to the high shear environment that occurs due to interfascicular sliding (Thorpe et al, 2012, Thorpe et al, 2015b). These findings suggest that there is greater turnover of ECM proteins localised to the IFM than within the fascicular matrix (FM) to repair local microdamage and maintain tendon homeostasis
Results reveal a diverse rate of protein turnover in both the FM and IFM, with values for individual proteins similar to those observed when the tendon matrix was analysed as a whole
Summary
Maintaining the structural and mechanical integrity of tissues in the musculoskeletal system, and other connective tissues, is fundamental to sustain tissue homeostasis and healthy function, requiring protein synthesis and degradation to repair and/or replace damaged tissue before damage accumulates and leads to injury (Humphrey et al, 2014). Other studies have measured relatively rapid collagen synthesis in tendon, both at basal levels and in response to exercise (Miller et al, 2005), and identified soluble collagen with a much shorter halflife compared to the majority of collagen in human articular cartilage (Hsueh et al, 2019); the location(s) of these more labile proteins remain to be identified. When taken together, these contradictory findings indicate that proteome dynamics in connective tissues is complex, and that the glycoprotein-rich phase may be replenished more rapidly than the collagen-rich phase. The turnover rate of individual proteins within the different phases of the extracellular matrix (ECM), and the potential contribution of differential regulation of protein turnover to maintenance of tissue homeostasis remain undefined
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