Importance of mechanical cues in regulating musculoskeletal circadian clock rhythmicity: Implications for articular cartilage.

The circadian clock, a collection of endogenous cellular oscillators with an approximate 24-h cycle, involves autoregulatory transcriptional/translational feedback loops to enable synchronization within the body. Circadian rhythmicity is controlled by a master clock situated in the hypothalamus; however, peripheral tissues are also under the control of autonomous clocks which are coordinated by the master clock to regulate physiological processes. Although light is the primary signal required to entrain the body to the external day, non-photic zeitgeber including exercise also entrains circadian rhythmicity.

Delayed reorganisation of F-actin cytoskeleton and reversible chromatin condensation in scleral fibroblasts under simulated pathological strain.

Mechanical loading regulates the functional capabilities of the ocular system, particularly in the sclera ('white of the eye') - the principal load-bearing tissue of the ocular globe. Resident fibroblasts of the scleral eye wall are continuously subjected to fluctuating mechanical strains arising from eye movements, cerebrospinal fluid pressure and, most influentially, intra-ocular pressure (IOP). Whilst fibroblasts are hypothesised to actively participate in scleral biomechanics, to date limited information has been reported on how the macroscopic stresses and strains are transmitted via their cytoskeletal networks.

Mechanical Cues: Bidirectional Reciprocity in the Extracellular Matrix Drives Mechano-Signalling in Articular Cartilage.

The composition and organisation of the extracellular matrix (ECM), particularly the pericellular matrix (PCM), in articular cartilage is critical to its biomechanical functionality; the presence of proteoglycans such as aggrecan, entrapped within a type II collagen fibrillar network, confers mechanical resilience underweight-bearing. Furthermore, components of the PCM including type VI collagen, perlecan, small leucine-rich proteoglycans-decorin and biglycan-and fibronectin facilitate the transduction of both biomechanical and biochemical signals to the residing chondrocytes, thereby regulating the process of mechanotransduction in cartilage. In this review, we summarise the literature reporting on the bidirectional reciprocity of the ECM in chondrocyte mechano-signalling and articular cartilage homeostasis.

Regulation of microRNA-221, -222, -21 and -27 in articular cartilage subjected to abnormal compressive forces.

Key Points: microRNAs (miRs) are small non-coding molecules that regulate post-transcriptional target gene expression. miRs are involved in regulating cellular activities in response to mechanical loading in all physiological systems, although it is largely unknown whether this response differs with increasing magnitudes of load. miR-221, miR-222, miR-21-5p and miR-27a-5p were significantly increased in ex vivo cartilage explants subjected to increasing load magnitude and in in vivo joint cartilage exposed to abnormal loading.

3D immuno-confocal image reconstruction of fibroblast cytoskeleton and nucleus architecture.

Computational models of cellular structures generally rely on simplifying approximations and assumptions that limit biological accuracy. This study presents a comprehensive image processing pipeline for creating unified three-dimensional (3D) reconstructions of the cell cytoskeletal networks and nuclei. Confocal image stacks of these cellular structures were reconstructed to 3D isosurfaces (Imaris), then tessellations were simplified to reduce the number of elements in initial meshes by applying quadric edge collapse decimation with preserved topology boundaries (MeshLab).

AMPA/kainate glutamate receptor antagonists prevent posttraumatic osteoarthritis.

Musculoskeletal disorders represent the third greatest burden in terms of death and disability in the developed world. Osteoarthritis is the single greatest cause of chronic pain, has no cure, and affects 8.5 and 27 million people in the UK and US, respectively.

Quantification of collagen fiber structure using second harmonic generation imaging and two-dimensional discrete Fourier transform analysis: Application to the human optic nerve head.

Second harmonic generation (SHG) microscopy is widely used to image collagen fiber microarchitecture due to its high spatial resolution, optical sectioning capabilities and relatively nondestructive sample preparation. Quantification of SHG images requires sensitive methods to capture fiber alignment. This article presents a two-dimensional discrete Fourier transform (DFT)-based method for collagen fiber structure analysis from SHG images.

Inflammatory and degenerative phases resulting from anterior cruciate rupture in a non-invasive murine model of post-traumatic osteoarthritis.

Joint injury is the predominant risk factor for post-traumatic osteoarthritis development (PTOA). Several non-invasive mouse models mimicking human PTOA investigate molecular mechanisms of disease development; none have characterized the inflammatory response to this acute traumatic injury. Our aim was to characterize the early inflammatory phase and later degenerative component in our in vivo non-invasive murine model of PTOA induced by anterior cruciate ligament (ACL) rupture.

Variation in electrosurgical vessel seal quality along the length of a porcine carotid artery.

Electrosurgical vessel sealing has been demonstrated to have benefits for both patients and practitioners, but significant variation in the strength of the seal continues to be a concern. This study aims to examine the variation in electrosurgical seal quality along the length of a porcine common carotid artery and explore the relationships between seal quality, vessel size and morphology. Additionally, the study aimed to investigate the minimum safety threshold for successful seals and the influence of vessel characteristics on meeting this requirement.

Effects of the mycotoxin nivalenol on bovine articular chondrocyte metabolism in vitro.

Objective: Kashin-Beck Disease (KBD) is an endemic, age-related degenerative osteoarthropathy and its cause is hypothesised to involve Fusarium mycotoxins. This study investigated the Fusarium mycotoxin Nivalenol (NIV) on the metabolism of bovine articular chondrocytes in vitro.

Design: The effect 0.

Effects of Wnt3A and mechanical load on cartilage chondrocyte homeostasis.

Introduction: Articular cartilage functions in withstanding mechanical loads and provides a lubricating surface for frictionless movement of joints. Osteoarthritis, characterised by cartilage degeneration, develops due to the progressive erosion of structural integrity and eventual loss of functional performance. Osteoarthritis is a multi-factorial disorder; two important risk factors are abnormal mechanical load and genetic predisposition.

Experience-dependent plasticity acts via GluR1 and a novel neuronal nitric oxide synthase-dependent synaptic mechanism in adult cortex.

Synaptic plasticity directs development of the nervous system and is thought to underlie memory storage in adult animals. A great deal of our current understanding of the role of AMPA receptors in synaptic plasticity comes from studies on developing cortex and cell cultures. In the present study, we instead focus on plasticity in mature neurons in the neocortex of adult animals.

Fibroblast growth factor 2 and transforming growth factor β1 induce precocious maturation of articular cartilage.

Objective: We have discovered that a combination of fibroblast growth factor 2 and transforming growth factor β1 induce profound morphologic changes in immature articular cartilage. The purpose of this study was to test the hypothesis that these changes represent accelerated postnatal maturation.

Methods: Histochemical and biochemical assays were used to confirm the nature of the morphologic changes that accompany growth factor stimulation of immature bovine articular cartilage explants in serum-free culture medium.

Eicosapentaenoic acid and docosahexaenoic acid reduce interleukin-1β-mediated cartilage degradation.

Introduction: In inflammatory joint disease, such as osteoarthritis (OA), there is an increased level of proinflammatory cytokines, such as interleukin (IL)-1β. These cytokines stimulate the production of matrix metalloproteinases (MMPs), which leads to the degradation of the cartilage extracellular matrix and the loss of key structural components such as sulphated glycosaminoglycan (sGAG) and collagen II. The aim of this study was to examine the therapeutic potential of n-3 polyunsaturated fatty acids (PUFAs) in an in vitro model of cartilage inflammation.

Boswellia frereana (frankincense) suppresses cytokine-induced matrix metalloproteinase expression and production of pro-inflammatory molecules in articular cartilage.

The aim of this study was to assess the anti-inflammatory efficacy of Boswellia frereana extracts in an in vitro model of cartilage degeneration and determine its potential as a therapy for treating osteoarthritis. Cartilage degradation was induced in vitro by treating explants with 5 ng/ml interleukin1alpha (IL-1alpha) and 10 ng/ml oncostatin M (OSM) over a 28-day period, in the presence or absence of 100 microg/ml B. frereana.

Involvement of the cytoskeletal elements in articular cartilage homeostasis and pathology.

The cytoskeleton of all cells is a three-dimensional network comprising actin microfilaments, tubulin microtubules and intermediate filaments. Studies in many cell types have indicated roles for these cytoskeletal proteins in many diverse cellular processes including alteration of cell shape, movement of organelles, migration, endocytosis, secretion, cell division and extracellular matrix assembly. The cytoskeletal networks are highly organized in structure enabling them to fulfil their biological functions.

Zonal variations in cytoskeletal element organization, mRNA and protein expression in the intervertebral disc.

The intervertebral disc is important in maintaining flexibility and dissipating loads applied to the spine. The disc comprises a heterogeneous population of cells, including those of the nucleus pulposus and annulus fibrosus, which are diverse in phenotype, partly due to the different mechanical loads they experience. Several studies have implicated the cytoskeleton in mechanotransduction, but little characterization of the three major cytoskeletal elements--actin, tubulin and vimentin--in the intervertebral disc has been undertaken.

The potential of IGF-1 and TGFbeta1 for promoting "adult" articular cartilage repair: an in vitro study.

Research into articular cartilage repair, a tissue unable to spontaneously regenerate once injured, has focused on the generation of a biomechanically functional repair tissue with the characteristics of hyaline cartilage. This study was undertaken to provide insight into how to improve ex vivo chondrocyte amplification, without cellular dedifferentiation for cell-based methods of cartilage repair. We investigated the effects of insulin-like growth factor 1 (IGF-1) and transforming growth factor beta 1 (TGFbeta1) on cell proliferation and the de novo synthesis of sulfated glycosaminoglycans and collagen in chondrocytes isolated from skeletally mature bovine articular cartilage, whilst maintaining their chondrocytic phenotype.

NCAM and PSA-NCAM dependent membrane spreading and F-actin reorganization in suspended adhering neural cells.

Mediation of synchronous cell-cell interactions by NCAM and PSA-NCAM is examined here in aggregates (monolayers) of C6 polysialylated embryonic neural cells, formed rapidly (within 30 s) in suspension in an ultrasound trap. These cells express all three main isoforms of neural cell adhesion molecule (NCAM). The rate of extension of perimeter contact (i.

Mechanical regulation of matrix metalloproteinases.

Matrix metalloproteinases can degrade and modify almost all components of the extracellular matrix hence their enzymatic activity is tightly regulated under physiological conditions. Primary modes of enzyme regulation include transcriptional control, zymogen activation and dynamic inhibition by tissue inhibitors of matrix metalloproteinases. Recent studies have demonstrated that mechanical regulation of matrix metalloproteinases largely operate through these regulatory pathways.

Disassembly of the vimentin cytoskeleton disrupts articular cartilage chondrocyte homeostasis.

Articular cartilage functions in dissipating forces applied across joints. It comprises an extracellular matrix containing primarily collagens, proteoglycans and water to maintain its functional properties, and is interspersed with chondrocytes. The chondrocyte cytoskeleton comprises actin microfilaments, tubulin microtubules and vimentin intermediate filaments.

The effect of cyclical compressive loading on gene expression in articular cartilage.

Osteoarthritis (OA) develops as a consequence of articular cartilage degeneration possibly initiated by excessive or abnormal loading of the joint, and potentially mediated through a proteinase/proteinase inhibitor imbalance. We have shown previously that physiological loads (0.5 MPa, 1 Hz, 3 hour) elicit increased expression and activation of the matrix metalloproteinases (MMPs) in articular cartilage explants in vitro.