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Structure-function Relationships in Human Tendons: Interfascicular Matrix Specialisation in the Achilles Tendon C4PR_LIV

ABSTRACT: Tendon is a highly aligned connective tissue, in which the macro-structure consists of collagen-rich fascicles surrounded by interfascicular matrix (IFM). In a series of recent studies in equine tissue, we have demonstrated specialisation of tendon composition, structure and mechanics to achieve the tendon’s functional requirements, specifically reporting extensive specialisation of the IFM region in the energy storing superficial digital flexor tendon. We have also demonstrated loss of functional specialisms with ageing, leading to a hypothesised new paradigm for tendinopathy, focused on the importance of the IFM. However, to date, there have been no studies focused on structure-function specialisation or the IFM in functionally distinct human tendons. Here, we compare the positional anterior tibialis tendon and energy storing Achilles tendon, performing a detailed analysis of the composition and mechanical properties of both fascicle and IFM regions, to test the hypothesis that the IFM in the energy storing Achilles tendon has specialised composition and mechanical properties, and that these specialisations are lost with ageing. We demonstrate that the IFM is specialised in the energy storing Achilles tendon, with greater elasticity and fatigue resistance than in the positional anterior tibialis tendon. While there were few age-related alterations in mechanics, we did identify age-related alterations in the IFM proteome of the Achilles tendon specifically, which is predicted to be regulated by TGF-beta signalling and may be responsible for the trend towards decreased fatigue resistance observed in the Achilles IFM with ageing.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Tendon

SUBMITTER: Deborah Simpson

LAB HEAD: Professor Hazel Screen

PROVIDER: PXD018212 | Pride | 2020-11-11

REPOSITORIES: Pride

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Source:

			Action	DRS
	ATT_040815_L_FM.mgf	Mgf
	ATT_040815_L_FM.mzid.gz	Mzid
	ATT_040815_L_FM.pride.mgf.gz	Mgf
	ATT_040815_L_FM.pride.mztab.gz	Mztab
	ATT_040815_L_FM.raw	Raw

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Project description:Healing process after connective tissues (CT) injury is complex but important as CT are critical for human moving, and patient outcome of CT injured patients is protracted with high individual variation. Specific markers which could be used for healing prognosis will be great help to monitor patient outcome, and furtherly improve target treatment and patient recovery. Although several common factors like age, gender and body mass index (BMI) were reported to predict ATR healing outcome [references], more specific markers which can be used as predictors of patient outcome after ATR are still lacking. Several biomarkers have been reported to associate with tendon healing, and indicated their relationship with patient outcome(1-4). These results highlight the potential of protein expression detection and analysis for tendon study in general and healing outcome prognosis in particular. Collagen type I (Col1a1) is the main component of Achilles tendon and plays vital role in tendon healing via involving in collagen fibrils production among tendon fibroblasts(5). Higher production of Col1a1 is associated with faster tendon repair(6), previous study on animal model reported the increased Col1a1 synthesis can exert a positive effect on tendon healing[?]. Thus, functional proteins with high impact on Col1a1 can be used not only to improve tendon healing, also can be as targets for healing improvement and outcome prediction. The proteome file of Achilles tendon which is important to increase understanding of tendon healing and help to identify accurate outcome-related biomarkers is however lagged behind. The identification of proteomic profile of Achilles tendon is very much limited in number of proteins and sample size(7-9), and is even few on human. Recent improvement in proteomic assay based on mass spectrometry (MS) made it possible to assemble the proteomic landscape of human tissues(10, 11) with high quality and sensitivity. To characterize the proteomic components in human Achilles tendon, we utilized biopsies from ATR patients with both good and poor 1-year healing outcome. A validated platform including quantitative MS and clinical database was used to identify proteomic landscape and potential bio-predictors of clinical outcome. Our study may provide a more comprehensive landscape of proteins for human Achilles tendon, as well as specific biomarkers which can be used for long term outcome prognosis after ATR.

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Structure-function Relationships in Human Tendons: Interfascicular Matrix Specialisation in the Achilles Tendon C4PR_LIV

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