Changes in the composition of the extracellular matrix in patellar tendinopathy

Samiric, Tom; Parkinson, John; Ilic, Mirna Z.; Cook, Jill; Feller, Julian A.; Handley, Christopher J.

doi:10.1016/j.matbio.2009.04.001

Cited by 127 publications

(53 citation statements)

References 42 publications

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“…Other studies have identified changes in the composition and structure of the ACL with age [10], but others have found no correlation with age in normal PT [103]. Nonetheless, these data suggest that there are key compositional differences between ACL and PT, and provide new insight as to pathways which may be involved in ACL injury, and potentially in the differential injury response of female ACL.…”

Section: Discussionmentioning

confidence: 75%

Proteomic Differences between Male and Female Anterior Cruciate Ligament and Patellar Tendon

et al. 2014

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The risk of anterior cruciate ligament (ACL) injury and re-injury is greater for women than men. Among other factors, compositional differences may play a role in this differential risk. Patellar tendon (PT) autografts are commonly used during reconstruction. The aim of the study was to compare protein expression in male and female ACL and PT. We hypothesized that there would be differences in key structural components between PT and ACL, and that components of the proteome critical for response to mechanical loading and response to injury would demonstrate significant differences between male and female. Two-dimensional liquid chromatography-tandem mass spectrometry and a label-free quantitative approach was used to identify proteomic differences between male and female PT and ACL. ACL contained less type I and more type III collagen than PT. There were tissue-specific differences in expression of proteoglycans, and ACL was enriched in elastin, tenascin C and X, cartilage oligomeric matrix protein, thrombospondin 4 and periostin. Between male and female donors, alcohol dehydrogenase 1B and complement component 9 were enriched in female compared to male. Myocilin was the major protein enriched in males compared to females. Important compositional differences between PT and ACL were identified, and we identified differences in pathways related to extracellular matrix regulation, complement, apoptosis, metabolism of advanced glycation end-products and response to mechanical loading between males and females. Identification of proteomic differences between male and female PT and ACL has identified novel pathways which may lead to improved understanding of differential ACL injury and re-injury risk between males and females.

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Section: Discussionmentioning

confidence: 75%

Proteomic Differences between Male and Female Anterior Cruciate Ligament and Patellar Tendon

et al. 2014

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“…The trypsinate was collected, centrifuged at 430 × g for 5 min, and cell pellet discarded. Each sample was analyzed in duplicate by adding 20 μl to a 96 well plate, followed by 180 μl of dimethylmethylene blue (DMMB) reagent [57, 58]. After 5 min of incubation, absorbance was determined at 525 nm with Multiskan Ascent microplate reader.…”

Section: Methodsmentioning

confidence: 99%

CRISPR/Cas9 knockout of HAS2 in rat chondrosarcoma chondrocytes demonstrates the requirement of hyaluronan for aggrecan retention

et al. 2016

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Hyaluronan (HA) plays an essential role in cartilage where it functions to retain aggrecan. Previous studies have suggested that aggrecan is anchored indirectly to the plasma membrane of chondrocytes via its binding to cell-associated HA. However, reagents used to test these observations such as hyaluronidase and HA oligosaccharides are short term and may have side activities that complicate interpretation. Using the CRISPR/Cas9 gene editing approach, a model system was developed by generating HA-deficient chondrocyte cell lines. HA synthase-2 (Has2)-specific single guide RNA was introduced into two different variant lines of rat chondrosarcoma chondrocytes; knockout clones were isolated and characterized. Two other members of the HA synthase gene family were expressed at very low relative copy number but showed no compensatory response in the Has2 knockouts. Wild type chondrocytes of both variants exhibited large pericellular matrices or coats extending from the plasma membrane. Addition of purified aggrecan monomer expanded the size of these coats as the proteoglycan became retained within the pericellular matrix. Has2 knockout chondrocytes lost all capacity to assemble a particle-excluding pericellular matrix and more importantly, no matrices formed around the knockout cells following the addition of purified aggrecan. When grown as pellet cultures so as to generate a bioengineered neocartilage tissue, the Has2 knockout chondrocytes assumed a tightly-compacted morphology as compared to the wild type cells. When knockout chondrocytes were transduced with Adeno-ZsGreen1-mycHas2, the cell-associated pericellular matrices were restored including the capacity to bind and incorporate additional exogenous aggrecan into the matrix. These results suggest that HA is essential for aggrecan retention and maintaining cell separation during tissue formation.

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“…Normal tendon primarily contains type I collagen that is hierarchically arranged into parallel-aligned fibrils, fibers, and fascicles. 31,64,76,80 This uniform alignment of fibers can be visualized in normal tendons using ultrasound imaging at the fascicle level (FIGURE 1). Water and noncollagenous proteins, such as proteoglycans, are present between the fibers and fascicles, which allow tendon lengthening through interfascicular sliding rather than fiber extension.…”

Section: Features Of Normal and Pathological Tendons On Imagingmentioning

confidence: 96%

Tendinopathy: Is Imaging Telling Us the Entire Story?

Docking¹,

Ooi²,

Connell³

2015

Journal of Orthopaedic & Sports Physical Therapy

149

132

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Synopsis Tendinopathy is frequently associated with structural disorganization within the tendon. As such, the clinical use of ultrasound and magnetic resonance imaging for tendinopathy has been the focus of numerous academic studies and clinical discussions. However, similar to other musculoskeletal conditions (osteoarthritis and intervertebral disc degeneration), there is no direct link between tendon structural disorganization and clinical symptoms, with findings on imaging potentially creating a confusing clinical picture. While imaging shows the presence and extent of structural changes within the tendon, the clinical interpretation of the images requires context in regard to the features of pain and the aggravating loads. This review will critically evaluate studies that have investigated the accuracy and sensitivity of imaging in the detection of clinical tendinopathy and the methodological issues associated with these studies (subject selection, lack of a robust gold standard, reliance on subjective measures). The advent of new imaging modalities allowing for the quantification of tendon structure or mechanical properties has allowed new critical insight into tendon pathology. A strength of these novel modalities is the ability to quantify properties of the tendon. Research utilizing ultrasound tissue characterization and sonoelastography will be discussed. This narrative review will also attempt to synthesize current research on whether imaging can predict the onset of pain or clinical outcome, the role of monitoring tendon structure during rehabilitation (ie, does tendon structure need to improve to get a positive clinical outcome?), and future directions for research, and to propose the clinical role of imaging in tendinopathy. J Orthop Sports Phys Ther 2015;45(11):842–852. Epub 21 Sep 2015. doi:10.2519/jospt.2015.5880

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Changes in the composition of the extracellular matrix in patellar tendinopathy

Cited by 127 publications

References 42 publications

Proteomic Differences between Male and Female Anterior Cruciate Ligament and Patellar Tendon

Proteomic Differences between Male and Female Anterior Cruciate Ligament and Patellar Tendon

CRISPR/Cas9 knockout of HAS2 in rat chondrosarcoma chondrocytes demonstrates the requirement of hyaluronan for aggrecan retention

Tendinopathy: Is Imaging Telling Us the Entire Story?

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