Glycosaminoglycans of human rotator cuff tendons: changes with age and in chronic rotator cuff tendinitis.

Abstract

Objectives-To analyse the glycosaminoglycans of the adult human rotator cuff tendon matrix, to characterise changes in the glycosaminoglycan composition with age and in chronic rotator cuff tendinitis. Methods-Rotator cuff (supraspinatus) tendons (n = 84) and common biceps tendons (n = 26) were obtained from cadavers with no history of tendon pathology (age range 11-95 years). Biopsies of rotator cuff tendons (supraspinatus and subscapularis tendons, n = 53) were Conclusions-The normal supraspinatus tendon has the proteoglycan/glycosaminoglycan of tendon fibrocartilage, which it is suggested is an adaptation to mechanical forces (tension, compression and shear) which act on the rotator cuff tendons in the shoulder, although other factors such as reduced vascularity, low oxygen tension and the influence of local growth factors may also be important. This functional adaptation may have important consequences for the structural strength of the supraspinatus tendon and to influence the ability of the tendon to repair after injury. The glycosaminoglycan composition of tendon specimens from patients with chronic tendinitis is consistent with acute inflammation and new matrix proteoglycan synthesis, even in relatively old tendon specimens and after at least one injection of corticosteroid. (Ann Rheum Dis 1994; 53: 367-376) Chronic shoulder pain is a common and disabling condition that is often seen in rheumatological practice and prevalent in the elderly community.1 1 Relatively little is known about the underlying pathology, as surgical biopsies of human tendons are rarely obtained and are not required for diagnosis. The main causes of shoulder pain are lesions of the rotator cuff tendons, most commonly the supraspinatus tendon, although the subscapularis, infraspinatus and teres minor Riley, Harrall, Constant, Chard, Cawston, Hazleman tendons may also be involved.3 The clinical description of 'tendinitis' is often used to describe painful tendon lesions, although there is little evidence for an acute inflammatory process in degenerate and spontaneously ruptured tendons. Rotator cuff tendinitis does not necessarily resolve with time and is often refractory to conservative therapies, including rest, physiotherapy and local corticosteroid injections.4 5Degeneration of the tendon matrix is generally considered to predispose to 'tendinitis' and eventual rupture, as normal tendons are immensely strong under tension.6 A variety of factors including ageing, vascular insufficiency, the anatomical shape of the acromium, impingement against osteophytes, and repetitive activities have all been implicated in the pathology of rotator cuff tendinitis.7 8 Whatever the cause, the most frequent site of all tendon lesions is the 'critical zone' in the supraspinatus tendon, approximately one centimetre from the bone insertion and a region of blood vessel anastomoses.9Although they form a minor proportion of the extracellular matrix, proteoglycans and their constituent glycosaminoglycans can influence many important physiolo...

Matrix metalloproteinase activities and their relationship with collagen remodelling in tendon pathology

“…By using aspartic acid racemisation data as a molecular clock, we showed that (particularly after the age of 60 years) significant amounts of protein remodelling have occurred, confirming our previous pentosidine data (Bank et al, 1999). This represents mainly collagen turnover, since previous work has shown that there is no change in the non-collagen component of these tendon that would account for the observed change in % D-Asp (Riley et al, 1994b). The D-Asp levels in normal supraspinatus are sometimes less than 50% of what would have been expected under conditions of undisturbed tissue ageing.…”

“…We have recently shown that there is also a reduction in MMP-3 expression in chronic Achilles tendinopathy, in lesions where there is no macroscopic tendon rupture (Ireland et al, 2001). The decrease in MMP-3 (coupled with an increase in proteoglycan gene expression) may account for the increased proteoglycan often found in degenerate tendons (Chard et al, 1994;Riley et al, 1994b). However, MMP-3 has activity against a broad range of substrates and is thought to play a major role in the activation of other MMPs (van Meurs et al, 1999).…”

Modulation of aggrecan and ADAMTS expression in ovine tendinopathy induced by altered strain

“…This indicates that common morphologic and histopathologic changes in tendon may belie very different underlying molecular pathologic processes. Increased GAG is a feature of painful (tendinopathy) and ruptured tendons in humans (13,27), and we found increased toluidine blue staining in both stress-deprived and overstressed tensile tendon (regions 3 and 4, respectively). However, findings of our gene expression studies suggest that the observed increase in chondroitin and keratan sulfate ( Figure 3) may be associated with versican and lumican in region 3 but with aggrecan in region 4.…”

“…shown that a number of molecular changes occur within the diseased tendon, including altered content and expression of collagen and proteoglycan (PG) and expression of matrix-degrading enzymes (6)(7)(8)(9)(10)(11)(12)(13)(14). However, which if any of these changes precede and lead to rupture, and which are a consequence of tearing is unknown.…”

The Basic Science of Tendinopathy

“…Animal studies demonstrate biglycan may serve both a structural [109] and a signaling role [77] in developing tendon and biglycan and collagen VI are coexpressed in tendon development [61]. It is possible the presence of tendon fibrocartilage proteoglycan/glycosaminoglycan in normal supraspinatus is part of a normal functional adaptation to mechanical forces in tendon [91]. * Using selective proteolysis of denatured collagen by alpha-chymotrypsin as described by Bank et al [14].…”