Electrospun Scaffold Micro-Architecture Induces an Activated Transcriptional Phenotype within Tendon Fibroblasts.

Biomaterial augmentation of surgically repaired rotator cuff tendon tears aims to improve the high failure rates (∼40%) of traditional repairs. Biomaterials that can alter cellular phenotypes through the provision of microscale topographical cues are now under development. We aimed to systematically evaluate the effect of topographic architecture on the cellular phenotype of fibroblasts from healthy and diseased tendons.

Loss of mutual protection between human osteoclasts and chondrocytes in damaged joints initiates osteoclast-mediated cartilage degradation by MMPs.

Osteoclasts are multinucleated, bone-resorbing cells. However, they also digest cartilage during skeletal maintenance, development and in degradative conditions including osteoarthritis, rheumatoid arthritis and primary bone sarcoma. This study explores the mechanisms behind the osteoclast-cartilage interaction.

Trends in the theory that inflammation plays a causal role in tendinopathy: a systematic review and quantitative analysis of published reviews.

Background/aims: The contribution of inflammation to tendinopathy has been debated in the scientific literature. Several factors may contribute to this lack of clarity, including inconsistent definitions of inflammation. We hypothesised that the adoption and/or rejection of a causal link between inflammation and tendinopathy varied as a function of the 'inflammatory component' (eg, immune cell and molecular mediators included in published reviews).

Presence of IL-17 in synovial fluid identifies a potential inflammatory osteoarthritic phenotype.

Purpose: Osteoarthritis (OA) is a common and heterogeneous arthritic disorder. Patients suffer pain and their joints are characterized by articular cartilage loss and osteophyte formation. Risk factors for OA include age and obesity with inflammation identified as a key mediator of disease pathogenesis.

Profibrotic mediators in tendon disease: a systematic review.

Background: Tendon disease is characterized by the development of fibrosis. Transforming growth factor beta (TGF-β), bone morphogenic proteins (BMPs) and connective tissue growth factor (CTGF) are key mediators in the pathogenesis of fibrotic disorders. The aim of this systematic review was to investigate the evidence for the expression of TGF-β, BMPs and CTGF along tendon disease progression and the response of tendon cells to these growth factors accordingly.

A comparative evaluation of the effect of polymer chemistry and fiber orientation on mesenchymal stem cell differentiation.

Bioengineered tissue scaffolds in combination with cells hold great promise for tissue regeneration. The aim of this study was to determine how the chemistry and fiber orientation of engineered scaffolds affect the differentiation of mesenchymal stem cells (MSCs). Adipogenic, chondrogenic, and osteogenic differentiation on aligned and randomly orientated electrospun scaffolds of Poly (lactic-co-glycolic) acid (PLGA) and Polydioxanone (PDO) were compared.

H3K27me3 demethylases regulate in vitro chondrogenesis and chondrocyte activity in osteoarthritis.

Background: Epigenetic changes (i.e., chromatin modifications) occur during chondrogenesis and in osteoarthritis (OA).

The chondrocyte-intrinsic circadian clock is disrupted in human osteoarthritis.

Peripheral clocks are essential for driving cell differentiation. In osteoarthritis, loss of the normal differentiated chondrocyte (cartilage cell) phenotype is causative of disease. We investigated whether clock gene expression differed in osteoarthritic compared to "healthy" chondrocytes and used RNAi to determine whether the differences observed could affect chondrocyte phenotype.

Comparison of transforming growth factor beta expression in healthy and diseased human tendon.

Background: Diseased tendons are characterised by fibrotic scar tissue, which adversely affects tendon structure and function and increases the likelihood of re-injury. The mechanisms and expression profiles of fibrosis in diseased tendon is understudied compared to pulmonary and renal tissues, where transforming growth factor (TGF)β and its associated superfamily are known to be key drivers of fibrosis and modulate extracellular matrix homeostasis. We hypothesised that differential expression of TGFβ superfamily members would exist between samples of human rotator cuff tendons with established disease compared to healthy control tendons.

Differences in glutamate receptors and inflammatory cell numbers are associated with the resolution of pain in human rotator cuff tendinopathy.

Introduction: The relationship between peripheral tissue characteristics and pain symptoms in soft tissue inflammation is poorly understood. The primary aim of this study was to determine immunohistochemical differences in tissue obtained from patients with persistent pain and patients who had become pain-free after surgical treatment for rotator cuff tendinopathy. The secondary aim was to investigate whether there would be differences in glutaminergic and inflammatory gene expression between disease-derived and healthy control cells in vitro.

In vitro effects of glutamate and N-methyl-D-aspartate receptor (NMDAR) antagonism on human tendon derived cells.

It is known that extracellular glutamate concentrations are increased in tendinopathy but the effects of glutamate upon human tendon derived cells are unknown. The primary purpose was to investigate the effect of glutamate exposure on human tendon-derived cells in terms of viability, protein, and gene expression. The second purpose was to assess whether NMDAR antagonism would affect the response of tendon-derived cells to glutamate exposure.

Glucocorticoids induce senescence in primary human tenocytes by inhibition of sirtuin 1 and activation of the p53/p21 pathway: in vivo and in vitro evidence.

Unlabelled: Cellular senescence is an irreversible side effect of some pharmaceuticals which can contribute to tissue degeneration.

Objective: To determine whether pharmaceutical glucocorticoids induce senescence in tenocytes.

Methods: Features of senescence (β-galactosidase activity at pH 6 (SA-β-gal) and active mammalian/mechanistic target of rapamycin (mTOR) in cell cycle arrest) as well as the activity of the two main pathways leading to cell senescence were examined in glucocorticoid-treated primary human tenocytes.

Aging mechanisms in arthritic disease.

Arthritic disease is one of the most common age-related pathologies worldwide. The erosion of cartilaginous tissues from articular surfaces within the joint and the failure to efficiently repair and regenerate this region with age lead to debilitating joint destruction, severe pain, and a crippling loss of function. In addition to the accumulative damage brought about by years of mechanical forces acting upon this region of tissue, there are also defects in underlying biological mechanisms which predispose the older population to excessive joint erosion.

BMP5 activates multiple signaling pathways and promotes chondrogenic differentiation in the ATDC5 growth plate model.

The bone morphogenetic protein 5 (BMP5) participates in skeletal development but its direct effects on the function of growth plate chondrocytes during chondrogenesis have not been explored. We have investigated the signaling pathways activated by BMP5 and its effect on chondrogenic differentiation in the ATDC5 growth plate chondrocyte model. BMP5 transiently activated p38 mitogen-activated protein kinase (MAPK) and extracellular signal-regulated kinase signaling after 10 days of differentiation; sustained Smad and p38 MAPK signaling were seen after 15 days differentiation.