Distribution and expression of type VI collagen and elastic fibers in human rotator cuff tendon tears

Abstract

There is increasing evidence for a progressive extracellular matrix change in rotator cuff disease progression. Directly surrounding the cell is the pericellular matrix, where assembly of matrix aggregates typically occurs making it critical in the response of tendon cells to pathological conditions. Studies in animal models have identified type VI collagen, fibrillin-1 and elastin to be located in the pericellular matrix of tendon and contribute in maintaining the structural and biomechanical integrity of tendon. However, there have been no reports on the localization of these proteins in human tendon biopsies. This study aimed to characterize the distribution of these ECM components in human rotator cuffs and gain greater insight into the relationship of pathology to tear size by analyzing the distribution and expression profiles of these ECM components. Confocal microscopy confirmed the localization of these structural molecules in the pericellular matrix of the human rotator cuff. Tendon degeneration led to an increased visibility of these components with a significant disorganization in the distribution of type VI collagen. At the genetic level, an increase in tear size was linked to an increased transcription of type VI collagen and fibrillin-1 with no significant alteration in the elastin levels. This is the first study to confirm the localization of type VI collagen, elastin and fibrillin-1 in the pericellular region of human supraspinatus tendon and assesses the effect of tendon degeneration on these structures, thus providing a useful insight into the composition of human rotator cuff tears which can be instrumental in predicting disease prognosis.

A quantitative label-free analysis of the extracellular proteome of human supraspinatus tendon reveals damage to the pericellular and elastic fibre niches in torn and aged tissue

“…Regardless of the absence of elastin, the observation that four different elastic fibre components were significantly less abundant in torn tendons, suggests a systematic damage to the fibrillin-rich microfibril niche. This is supported by a previous study, which observed a disturbance to fibrillin-rich elastic fibres in large and massive supraspinatus tears using confocal microscopy [5]. The impairment of this micro-environment, which serves as a repository for growth factors, and in particular TGF- β [35], may also help to explain the disruption of the TGF- β axis in tendinopathy [11].…”

“…It is known to interact directly with MAFP5 [33, 34], as well as LTBP2, with the latter targeting and sequestering TGF- β to the fibrillin-microfibril niche, as well as binding fibulins [35]. FBLN1 has been shown to co-localise with elastic fibres, but there is little information about its exact role [20, 36] The existence of fibillin-rich microfibrils in tendon has previously been described in fetal calf achilles [33], canine flexor digitorum profundus [37], bovine flexor tendon [3], and in human supraspinatus tendons, where they have been shown to be regularly distributed and in the vicinity of tendon cell arrays [5], with all these studies showing elastin to co-localise with the fibrillin microfibers. It is curious, therefore, in light of the high abundance of fibrillin-1 detected here and the use of elastase digestion as validation, that we did not detect any elastin peptides.…”

“…Collagen is thought to account for 65–80% and the fibrous protein elastin for approximately 1–2% of the dry mass of tendon in general [2], with the latter described to occur in elastic fibres approximately 0.3–2.0 μ m in diameter, broadly distributed throughout the tendon, localized longitudinally along cell arrays and between collagen fascicles [3]. The supraspinatus tendon is known to be poorly vascularised [4], with cell arrays embedded in a Collagen VI rich pericellular matrix [5]. Tears of this tendon are very common and are often painful and debilitating.…”

In vitro and in vivo effects of PDGF-BB delivery strategies on tendon healing: a review

“…collagen fibre organisation, needs to be addressed and improved. Changes in elastic fibres during tendon healing have not been studied in detail yet, but initial evidence suggests that there is an increase in fibrillin-1 synthesis accompanied with a small increase in elastin production (Thakkar et al, 2014). How this translates directly to the functional aspects of healed tendons is not clear yet.…”

Modelling approaches for evaluating multiscale tendon mechanics

“…Tendons also contain proteoglycans (PGs, i.e. decorin, fibromodulin, biglycan, lumican, aggrecan) in relatively small quantities, with types and amounts varying according to different species, ages and anatomical locations [11,[19][20][21]. In tendon, PGs have been found to play an important role in facilitating fibrillogenesis, regulating extracellular matrix assembly and modulating cellmatrix interaction [20,[22][23][24].…”