Increased expression of aggrecan and biglycan mRNA in Achilles tendinopathy

Corps, Anthony N.; Robinson, A. H. N.; Movin, Tomas; Costa, Matthew L.; Hazleman, B. L.; Riley, Graham P.

doi:10.1093/rheumatology/kei152

Cited by 126 publications

(106 citation statements)

References 15 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…In particular, aggrecan is likely to contribute to the regions of fibrocartilagenous metaplasia observed here (Milz et al 2005). Aggrecan mRNA levels were increased in Achilles tendinosis (Corps et al 2006) and in the ruptured supraspinatus (Lo et al 2005) whereas versican levels were unchanged compared to controls (Corps et al 2006). The discrepancy between findings at the protein and mRNA levels in these studies is consistent with a report from cartilage showing that versican protein can remain in the matrix long after mRNA levels have declined (Matsumoto et al 2006).…”

Section: Discussionsupporting

confidence: 79%

Increased versican content is associated with tendinosis pathology in the patellar tendon of athletes with jumper's knee

Scott

Lian

Roberts

et al. 2008

Scandinavian Med Sci Sports

View full text Add to dashboard Cite

Expansion of the extracellular matrix is a prominent but poorly characterized feature of tendinosis. The present study aimed to characterize the extent and distribution of the large aggregating proteoglycan versican in patients with patellar tendinosis. We obtained tendon from tendinopathy patients undergoing debridement of the patellar tendon and from controls undergoing intramedullary tibial nailing. Versican content was investigated by Western blotting and immunohistochemistry. Microvessel thickness and density were determined using computerassisted image analysis. Markers for smooth muscle (α-SMA), endothelial cells (CD31) and proliferating cells (Ki67) were examined immunohistochemically. Western blot analysis and immunohistochemical staining revealed elevated versican content in the proximal patellar tendon of tendinosis patients (p=0.042). Versican content was enriched in regions of fibrocartilage metaplasia and fibroblast proliferation, as well as in the perivascular matrix of proliferating microvessels and within the media and intima of arterioles. Microvessel density was higher in tendinosis tissue compared to control tissue. Versican deposition is a prominent feature of patellar tendinosis. Because this molecule is not only a component of normal fibrocartilagenous matrices, but is also implicated in a variety of soft tissue pathologies, future studies should further detail both pathological and adaptive roles of versican in tendons.

show abstract

Section: Discussionsupporting

confidence: 79%

Increased versican content is associated with tendinosis pathology in the patellar tendon of athletes with jumper's knee

Scott

Lian

Roberts

et al. 2008

Scandinavian Med Sci Sports

View full text Add to dashboard Cite

show abstract

“…Since we found unchanged type I collagen expression, decreased MMP-2 expression, and a trend toward an increased MMP-3 expression (P ϭ 0.07), it seems clear that the gene expression profile of the rat Achilles tendons subjected to 12 wk of running does not fit well with that of a tendinopathic tendon. In further support of this, we found decreased levels of VEGF and proteoglycan mRNA (fibromodulin and biglycan), which are thought to be elevated with tendinopathy (4,12,13,36,38). These mRNA results serve to underline the more fundamental finding of unchanged tissue histology, which clearly indicates that the training model does not induce Achilles tendinopathy.…”

Section: Regulation Of Gene Expressionsupporting

confidence: 69%

Uphill running improves rat Achilles tendon tissue mechanical properties and alters gene expression without inducing pathological changes

Heinemeier

Skovgaard

Bayer

et al. 2012

Journal of Applied Physiology

View full text Add to dashboard Cite

Little is known about the etiology of this disorder, and the development of a good animal model for overuse tendinopathy is essential for advancing insight into the disease mechanisms. Our aim was to test a previously proposed rat model for Achilles tendon overuse. Ten adult male Sprague-Dawley rats ran on a treadmill with 10°incline, 1 h/day, 5 days/wk (17-20 m/min) for 12 wk and were compared with 12 control rats. Histological, mechanical, and gene-expression changes were measured on the Achilles tendons after the intervention, and local tendon glucose-uptake was measured before and after the intervention with positron emission tomography. No differences were detected between runners and controls in tissue histology or in glucose uptake, indicating that tendon pathology was not induced. Greater tendon tissue modulus (P Ͻ 0.005) and failure stress/body weight (P Ͻ 0.02) in runners compared with controls further supported that tendons successfully adapted to uphill running. Several genes of interest were regulated after 12 wk of running. Expression of collagen III and insulin-like growth factor I was increased, while collagen I was unchanged, and decreases were seen in noncollagen matrix components (fibromodulin and biglycan), matrix degrading enzymes, transforming growth factor-␤1, and connective tissue growth factor. In conclusion, the tested model could not be validated as a model for Achilles tendinopathy, as the rats were able to adapt to 12 wk of uphill running without any signs of tendinopathy. Improved mechanical properties were observed, as well as changes in gene-expression that were distinctly different from what is seen in tendinopathy and in response to short-term tendon loading. loading; exercise; tendinopathy; collagen TENDONS TRANSMIT FORCE FROM muscle to bone during muscle contraction, and optimal, painless function of tendon tissue is essential in voluntary movement. Although tendons can withstand considerable force, repetitive movements can lead to overuse of tendon tissue, resulting in tendinopathy, which is characterized by pain during activity and significantly impaired performance (36). Tendinopathy is very common in relation to both sports and occupational loading (16,17,45), and, since treatment possibilities are still relatively poor, these conditions are often prolonged (36). Although the features of tendinopathy at the time point when symptoms occur are relatively well described, the etiology of overuse-related tendinopathy is still poorly understood. Thus we know that symptomatic human tendinopathy is characterized by histological changes, such as increased cell density, altered cell morphology, and disorganization of the collagen matrix (reviewed by Ref. 36). In addition, increased vascularization has been shown in tendinopathic tendon (8), and studies of gene expression commonly find higher levels of collagen I and III, proteoglycan, and matrix metalloproteinase (MMP)-2 mRNA, as well as decreased MMP-3 mRNA expression (3, 12-14, 26 -28). However, the events leading up to these chan...

show abstract

“…Downhill running increased aggrecan expression in rat supraspinatus tendon in association with increased type II collagen, but it is unclear whether this change occurs throughout the tendon or only in the attachment or subacromial compressed region (19). Elevated aggrecan expression has been reported in painful but not ruptured Achilles tendons (33) and torn rotator cuffs (34) in humans, although the precise location of the tendon sampled was not reported. It seems unlikely that the increased aggrecan expression observed in region 4 in our sheep was an adaptation to compressive loading, since other typical gene changes (such as increased biglycan and type II collagen) were absent.…”

Section: Discussionmentioning

confidence: 99%

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

Smith

Sakurai

Smith

et al. 2008

Arthritis & Rheumatism

View full text Add to dashboard Cite

Objective. To evaluate histologic, immunohistochemical, and molecular changes in tendon induced by altered strain in a large-animal model.Methods. A full-thickness partial-width laceration of the infraspinatus tendon was created in 5 sheep, while 5 sham-operated sheep were used as controls. Sheep were killed after 4 weeks, and 4 differentially stressed tendon regions (tensile or near bone attachment from overstressed or stress-deprived halves) were evaluated for histopathology, proteoglycan (PG) accumulation, and characterization of glycosaminoglycans and aggrecan catabolites. Gene expression of matrix components, enzymes, and inhibitors was analyzed by reverse transcriptase-polymerase chain reaction.Results. Histopathologic changes were detected in both overstressed and stress-deprived tensile tendon, but only in stress-deprived tendon near bone. In overstressed and stress-deprived tensile tendon, levels of keratan sulfate, chondroitin 4-sulfate, and chondroitin 6-sulfate were increased. In overstressed tensile tendon, levels of ADAMTS-generated aggrecan catabolites were increased. There was increased matrix metalloproteinase 13 (MMP-13) and decreased fibromodulin and decorin expression in all regions. Increased MMP-1, MMP-9, MMP-14, and ADAMTS-1 expression, and decreased type II collagen expression were restricted to stress-deprived tendon. In stress-deprived boneattachment regions, messenger RNA (mRNA) for aggrecan was decreased, and ADAMTS was increased. In overstressed tensile tendon, aggrecan mRNA was increased, and ADAMTS was decreased.Conclusion. The distinct molecular changes in adjacent tissue implicate altered strain rather than humoral factors in controlling abnormal tenocyte metabolism, and highlight the importance of regional sampling. Tendon abnormalities induced by increased strain are accompanied by increased aggrecan, decreased ADAMTS, and low PG expression, which may negatively impact the structural integrity of the tissue and predispose to rupture.Injuries of the shoulder due to overuse are increasingly prevalent in both the sporting arena and the workplace. Occupational injury of the shoulder is second only to neck and low back pain in the frequency of consultation by general practitioners, with the most common injury involving the rotator cuff. (1,2) The prevalence of rotator cuff conditions increases with age, from 30-50% in the seventh decade of life to a staggering 70-80% by the ninth (3,4). Although most cases are treated conservatively, many patients undergo surgical repair with a prolonged convalescence. There are no drugs to specifically treat disorders of the rotator cuff or other tendons, and many surgical repairs fail within 12 months (5). Lack of knowledge of the fundamental mechanisms that underlie tendon breakdown results in limited and inadequate management options for tendon disorders.

show abstract

Increased expression of aggrecan and biglycan mRNA in Achilles tendinopathy

Cited by 126 publications

References 15 publications

Increased versican content is associated with tendinosis pathology in the patellar tendon of athletes with jumper's knee

Increased versican content is associated with tendinosis pathology in the patellar tendon of athletes with jumper's knee

Uphill running improves rat Achilles tendon tissue mechanical properties and alters gene expression without inducing pathological changes

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

Contact Info

Product

Resources

About