Aggrecan in bovine tendon

Sakurai

et al. 2008

Arthritis & Rheumatism

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.

Section: Discussionmentioning

confidence: 99%

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

Sakurai

et al. 2008

Arthritis & Rheumatism

Journal Orthopaedic Research

“…8 Although GAG analysis alone does not determine what proportion of the chains are attached to aggrecan (compared to other CS/DS PG core proteins), purification steps such as gradient centrifugation and gel permeation chromatography, together with gel electrophoresis and protein sequence analysis, have been used to provide definitive evidence for the presence of aggrecan core protein in extracts of tendon. 3,9 Further, Western analysis with antibodies specific to known aggrecan core epitopes and neoepitopes 10 has shown the presence of both intact aggrecan and ADAMTS-generated fragments in the same tendon and ligament samples. 9,10 Aggrecan is most abundant in regions of tendon that experience mechanical compression and at tendon-bone insertion sites, 11 and proteolytically degraded aggrecan has also been identified by peptide analysis in tensional regions of normal adult tendons.…”

mentioning

confidence: 99%

“…The reparative task for cells, whether mature or progenitor, is primarily to re-establish the normal tensional properties of the tissue by the secretion and integration of newly synthesized collagen into the existing network, which is largely composed of heterotypic fibrils of collagens I and III along with minor amounts of type V. 1,2 This process also requires production and organization of a noncollagenous matrix which, among many other components, contains members of the collagen binding SLRP family and the large proteoglycans (PGs), versican, and aggrecan. 3 To date, there has been no clearly defined mechanistic role for aggrecan (or versican) in tendon cell behavior, matrix homeostatic maintenance, tissue injury, and repair. This may be because of the inherent difficulties involved in analysis of the small amount of aggrecan present in all noncartilaginous tissues.…”

mentioning

confidence: 99%

“…9,10 Aggrecan is most abundant in regions of tendon that experience mechanical compression and at tendon-bone insertion sites, 11 and proteolytically degraded aggrecan has also been identified by peptide analysis in tensional regions of normal adult tendons. 3 We have recently reported that diseased ligaments from horses with degenerative suspensory ligament desmitis (DSLD) contain highly elevated levels of intact aggrecan and fragments generated by ADAMTSaggrecanase activity. 10 ADAMTS5 (TS5) was also abundant in the affected ligaments, but it was found to be complexed with hyaluronan around chondroid cellular clusters, and no active forms could be detected in these extracts.…”

mentioning

confidence: 99%

See 1 more Smart Citation

Murine tendon function is adversely affected by aggrecan accumulation due to the knockout of ADAMTS5

Wang

Bell

Thakore

et al. 2011

Self Cite

The present study examined the effect of ADAMTS5 (TS5) knockout on the properties of murine flexor digitorum longus (FDL) and Achilles tendons. FDL and Achilles tendons were analyzed using biomechanical testing, histology, and immunohistochemistry; further characterization of FDL tendons was conducted using transmission electron microscopy (collagen fibril ultrastructure), SDS-PAGE (collagen content and type), fluorescence-assisted carbohydrate electrophoresis for chondroitin sulfate and hyaluronan, and Western blotting for aggrecan, versican, and decorin abundance and distribution. FDL tendons of TS5 À/À mice showed a 33% larger cross-sectional area, increased collagen fibril area fraction, and decreased material properties relative to those of wild type mice. In TS5 À/À mice, aggrecan accumulated in the pericellular matrix of tendon fibroblasts. In Achilles tendons, cross-sectional area, stress relaxation, and structural properties were similar in TS5 À/À and wild type mice; however, the TS5 À/À tendons exhibited a higher tensile modulus and a weakened enthesis. These results demonstrate that TS5 deficiency disturbs normal tendon collagen organization and alters biomechanical properties. Hence, the role of ADAMTS5 in tendon is to remove pericellular and interfibrillar aggrecan to maintain the molecular architecture responsible for normal tissue function. ß

Journal Orthopaedic Research

“…Similar variation can be seen in areas where tendons wrap around bony pulleys. The predicted increase in compressive stress at these locations has been correlated with an increase in a cartilage like extracellular matrix (e.g., aggrecan) [17]. Even in this well studied area, however, the bioinechanical properties of the compressed regions have never been measured and compared to the known biomechanical properties of the tendon.…”

mentioning

confidence: 99%

Variation of biomechanical, structural, and compositional properties along the tendon to bone insertion site

Thomopoulos

Williams

Gimbel

et al. 2003

392

128

The tendon to bone insertion site is a complex transitional region that links two very different materials. The insertion site must transfer a complex loading environment effectively to prevent injury and provide proper joint function. In order to accomplish this load transfer effectively, the properties of the insertion site were hypothesized to vary along its length. The quasilinear viscoelastic (QLV) Model was used to determine biomechanical properties, polarized light analysis was used to quantitate collagen orientation (structure), and in situ hybridization was used to determine the expression of extracellular matrix genes (composition). All assays were performed at two insertion site locations: the tendon end of the insertion and the bony end of the insertion. Biomechanically, the apparent properties of peak strain, the coefficients (A and B ) that describe the elastic component of the QLV model, and one of the coefficients ( 7 , ) of the viscous component of the model were significantly higher, while another of the coefficients ( C ) of the viscous component was significantly lower at the tendon insertion compared to the bony insertion. The collagen was significantly more oriented at the tendon insertion compared to the bony insertion. Finally, collagen types 11, IX, and X, and aggrecan were localized only to the bony insertion, while decorin and biglycan were localized only to the tendon insertion. Thus, the tendon to bony insertion site varies dramatically along its length in terms of its viscoelastic properties, collagen structure, and extracellular matrix composition.