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Current status of functional MRI of osteoarthritis for diagnosis and prognosis.
Juras, V, Chang, G, Regatte, RR
Current opinion in rheumatology. 2020;(1):102-109
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Abstract
PURPOSE OF REVIEW Osteoarthritis is a major source of disability, pain and socioeconomic cost worldwide. The epidemiology of the disorder is multifactorial including genetic, biological and biomechanical components, some of them detectable by MRI. This review provides the most recent update on MRI biomarkers which can provide functional information of the joint structures for diagnosis, prognosis and treatment response monitoring in osteoarthritis trials. RECENT FINDINGS Compositional or functional MRI can provide clinicians with valuable information on glycosaminoglycan content (chemical exchange saturation transfer, sodium MRI, T1ρ) and collagen organization (T2, T2, apparent diffusion coefficient, magnetization transfer) in joint structures. Other parameters may also provide useful information, such as volumetric measurements of joint structures or advanced image data postprocessing and analysis. Automated tools seem to have a great potential to be included in these efforts providing standardization and acceleration of the image data analysis process. SUMMARY Functional or compositional MRI has great potential to provide noninvasive imaging biomarkers for osteoarthritis. Osteoarthritis as a whole joint condition needs to be diagnosed in early stages to facilitate selection of patients into clinical trials and/or to measure treatment effectiveness. Advanced evaluation including machine learning, neural networks and multidimensional data analysis allow for wall-to-wall understanding of parameter interactions and their role in clinical evaluation of osteoarthritis.
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Functional MRI for evaluation of hyaline cartilage extracelullar matrix, a physiopathological-based approach.
Martín Noguerol, T, Raya, JG, Wessell, DE, Vilanova, JC, Rossi, I, Luna, A
The British journal of radiology. 2019;(1103):20190443
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Abstract
MRI of articular cartilage (AC) integrity has potential to become a biomarker for osteoarthritis progression. Traditional MRI sequences evaluate AC morphology, allowing for the measurement of thickness and its change over time. In the last two decades, more advanced, dedicated MRI cartilage sequences have been developed aiming to assess AC matrix composition non-invasively and detect early changes in cartilage not captured on morphological sequences. T2-mapping and T1ρ sequences can be used to estimate the relaxation times of water inside the AC. These sequences have been introduced into clinical protocols and show promising results for cartilage assessment. Extracelullar matrix can also be assessed using diffusion-weighted imaging and diffusion tensor imaging as the movement of water is limited by the presence of extracellular matrix in AC. Specific techniques for glycosaminoglycans (GAG) evaluation, such as delayed gadolinium enhanced MRI of cartilage or Chemical Exchange Saturation Transfer imaging of GAG, as well as sodium imaging have also shown utility in the detection of AC damage. This manuscript provides an educational update on the physical principles behind advanced AC MRI techniques as well as a comprehensive review of the strengths and weaknesses of each approach. Current clinical applications and potential future applications of these techniques are also discussed.
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The chondrocyte channelome: A narrative review.
Mobasheri, A, Matta, C, Uzielienè, I, Budd, E, Martín-Vasallo, P, Bernotiene, E
Joint bone spine. 2019;(1):29-35
Abstract
Chondrocytes are the main cells in the extracellular matrix (ECM) of articular cartilage and possess a highly differentiated phenotype that is the hallmark of the unique physiological functions of this specialised load-bearing connective tissue. The plasma membrane of articular chondrocytes contains a rich and diverse complement of membrane proteins, known as the membranome, which defines the cell surface phenotype of the cells. The membranome is a key target of pharmacological agents and is important for chondrocyte function. It includes channels, transporters, enzymes, receptors, and anchors for intracellular, cytoskeletal and ECM proteins and other macromolecular complexes. The chondrocyte channelome is a sub-compartment of the membranome and includes a complete set of ion channels and porins expressed in these cells. Many of these are multi-functional proteins with "moonlighting" roles, serving as channels, receptors and signalling components of larger molecular assemblies. The aim of this review is to summarise our current knowledge of the fundamental aspects of the chondrocyte channelome, discuss its relevance to cartilage biology and highlight its possible role in the pathogenesis of osteoarthritis (OA). Excessive and inappropriate mechanical loads, an inflammatory micro-environment, alternative splicing of channel components or accumulation of basic calcium phosphate crystals can result in an altered chondrocyte channelome impairing its function. Alterations in Ca2+ signalling may lead to defective synthesis of ECM macromolecules and aggravated catabolic responses in chondrocytes, which is an important and relatively unexplored aspect of the complex and poorly understood mechanism of OA development.
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[Cartilage/chondrocyte research and osteoarthritis. Mechanobiology for development of osteoarthritis.].
Ogawa, H, Akiyama, H
Clinical calcium. 2018;(6):789-795
Abstract
Articular cartilage is exquisitely sensitive to their mechanical environment, and mechanical loading may be the most important external factor regulating cartilage metabolism. Mechanical loading regulates chondrocyte activity, and pathological excessive loading leads to abnormal mechanotransduction, which in turn induces cartilage degradation. Several studies report that moderate levels of exercise exerts beneficial effects, such as improvements in pain and physical function, and also mitigates joint destruction through the down-regulation of the expression of matrix proteases. Calcium signaling is an initial step in chondrocyte mechanotransduction that has been linked to many cellular processes, and recent studies found that calcium ion channels distinctively mechanically activated by physiological or pathological mechanical loading through transient receptor potential vanilloid 4(TRPV4)or Piezo ion channels. We review here the recent progress on mechanotransduction of chondocytes, highlighting the calcium ion channels.
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Osteochondral Angiogenesis and Promoted Vascularization: New Therapeutic Target.
García-Fernández, L
Advances in experimental medicine and biology. 2018;:315-330
Abstract
The control of the different angiogenic process is an important point in osteochondral regeneration. Angiogenesis is a prerequisite for osteogenesis in vivo; insufficient neovascularization of bone constructs after scaffold implantation resulted in hypoxia and cellular necrosis. Otherwise, angiogenesis must be avoided in chondrogenesis; vascularization of the cartilage contributes to structural damage and pain. Finding a balance between these processes is important to design a successful treatment for osteochondral regeneration. This chapter shows the most important advances in the control of angiogenic process for the treatment of osteochondral diseases focused on the administration of pro- or anti-angiogenic factor and the design of the scaffold.
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[Cartilage/chondrocyte research and osteoarthritis. The role of microRNAs and extracellular vesicles in osteoarthritis pathogenesis.].
Miyaki, S
Clinical calcium. 2018;(6):783-788
Abstract
Extracellular vesicles(EV)have been emerged as carrier for the exchange of microRNAs and bioactive factors within cartilage and between joint tissues to promote joint homeostasis and osteoarthritis(OA)pathogenesis. The purpose of this review is to describe how microRNAs and EV regulate functions of chondrocytes in OA pathogenesis.
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Prestructural cartilage assessment using MRI.
Link, TM, Neumann, J, Li, X
Journal of magnetic resonance imaging : JMRI. 2017;(4):949-965
Abstract
UNLABELLED Cartilage loss is irreversible, and to date, no effective pharmacotherapies are available to protect or regenerate cartilage. Quantitative prestructural/compositional MR imaging techniques have been developed to characterize the cartilage matrix quality at a stage where abnormal findings are early and potentially reversible, allowing intervention to halt disease progression. The goal of this article is to critically review currently available technologies, present the basic concept behind these techniques, but also to investigate their suitability as imaging biomarkers including their validity, reproducibility, risk prediction and monitoring of therapy. Moreover, we highlighted important clinical applications. This review article focuses on the currently most relevant and clinically applicable technologies, such as T2 mapping, T2*, T1ρ, delayed gadolinium enhanced MRI of cartilage (dGEMRIC), sodium imaging and glycosaminoglycan chemical exchange saturation transfer (gagCEST). To date, most information is available for T2 and T1ρ mapping. dGEMRIC has also been used in multiple clinical studies, although it requires Gd contrast administration. Sodium imaging and gagCEST are promising technologies but are dependent on high field strength and sophisticated software and hardware. LEVEL OF EVIDENCE 5 J. Magn. Reson. Imaging 2017;45:949-965.
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The clinical presentation of individuals with femoral acetabular impingement and labral tears: A narrative review of the evidence.
Cheatham, SW, Enseki, KR, Kolber, MJ
Journal of bodywork and movement therapies. 2016;(2):346-55
Abstract
Femoral acetabular impingement (FAI) has emerged as one of the more commonly recognized intraarticular hip pathologies and is often accompanied with a labral tear. The understanding of the clinical characteristics of individuals with symptomatic FAI has evolved over the past several years due to emerging research. As research progresses, there is often a gap in translating the current evidence to clinical practice. This manuscript presents the latest evidence underpinning the clinical presentation of FAI and labral tears. Evidence is presented within the context of bridging the latest research and clinical practice.
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Osteoarthritis year in review 2015: biology.
Malfait, AM
Osteoarthritis and cartilage. 2016;(1):21-6
Abstract
This review highlights a selection of recently published literature in the area of osteoarthritis biology. Major themes transpiring from a PubMed search covering the year between the 2014 and the 2015 Osteoarthritis Research Society International (OARSI) World Congress are explored. Inflammation emerged as a significant theme, revealing complex pathways that drive dramatic changes in cartilage homeostasis and in the synovium. Highlights include a homeostatic role for CXC chemokines in cartilage, identification of the zinc-ZIP8-MTF1 axis as an essential regulator of cartilage catabolism, and the discovery that a small aggrecan fragment can have catabolic and pro-inflammatory effects through Toll-like receptor 2. Synovitis can promote joint damage, partly through alarmins such as S100A8. Synovitis and synovial expression of the pro-algesic neurotrophin, Nerve Growth Factor, are associated with pain. Increasingly, researchers are considering specific pathogenic pathways that may operate in distinct subsets of osteoarthritis associated with distinct risk factors, including obesity, age, and joint injury. In obesity, the contribution of metabolic factors and diet is under intense investigation. The role of autophagy and oxidative stress in age-related osteoarthritis has been further explored. This approach may open avenues for targeted treatment of distinct phenotypes of osteoarthritis. Finally, a small selection of novel analgesic targets in the periphery is briefly discussed, including calcitonin gene-related peptide and the neuronal sodium voltage-gated channels, Nav1.7 and Nav1.8.
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Chondrosenescence: definition, hallmarks and potential role in the pathogenesis of osteoarthritis.
Mobasheri, A, Matta, C, Zákány, R, Musumeci, G
Maturitas. 2015;(3):237-44
Abstract
Aging and inflammation are major contributing factors to the development and progression of arthritic and musculoskeletal diseases. "Inflammaging" refers to low-grade inflammation that occurs during physiological aging. In this paper we review the published literature on cartilage aging and propose the term "chondrosenescence" to define the age-dependent deterioration of chondrocyte function and how it undermines cartilage function in osteoarthritis. We propose the concept that a small number of senescent chondrocytes may be able to take advantage of the inflammatory tissue microenvironment and the inflammaging and immunosenescence that is concurrently occurring in the arthritic joint, further contributing to the age-related degradation of articular cartilage, subchondral bone, synovium and other tissues. In this new framework "chondrosenescence" is intimately linked with inflammaging and the disturbed interplay between autophagy and inflammasomes, thus contributing to the age-related increase in the prevalence of osteoarthritis and a decrease in the efficacy of articular cartilage repair. A better understanding of the basic mechanisms underlying chondrosenescence and its modification by drugs, weight loss, improved nutrition and physical exercise could lead to the development of new therapeutic and preventive strategies for osteoarthritis and a range of other age-related inflammatory joint diseases. Aging is inevitable but age-related diseases may be modifiable.