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International Journal of Molecular... Jun 2023Collagens serve essential mechanical functions throughout the body, particularly in the connective tissues. In articular cartilage, collagens provide most of the... (Review)
Review
Collagens serve essential mechanical functions throughout the body, particularly in the connective tissues. In articular cartilage, collagens provide most of the biomechanical properties of the extracellular matrix essential for its function. Collagen plays a very important role in maintaining the mechanical properties of articular cartilage and the stability of the ECM. Noteworthily, many pathogenic factors in the course of osteoarthritis and rheumatoid arthritis, such as mechanical injury, inflammation, and senescence, are involved in the irreversible degradation of collagen, leading to the progressive destruction of cartilage. The degradation of collagen can generate new biochemical markers with the ability to monitor disease progression and facilitate drug development. In addition, collagen can also be used as a biomaterial with excellent properties such as low immunogenicity, biodegradability, biocompatibility, and hydrophilicity. This review not only provides a systematic description of collagen and analyzes the structural characteristics of articular cartilage and the mechanisms of cartilage damage in disease states but also provides a detailed characterization of the biomarkers of collagen production and the role of collagen in cartilage repair, providing ideas and techniques for clinical diagnosis and treatment.
Topics: Humans; Osteoarthritis; Arthritis, Rheumatoid; Collagen; Extracellular Matrix; Cartilage, Articular
PubMed: 37372989
DOI: 10.3390/ijms24129841 -
RMD Open Feb 2024It is known that metabolic shifts and tissue remodelling precede the development of visible inflammation and structural organ damage in inflammatory rheumatic diseases... (Review)
Review
It is known that metabolic shifts and tissue remodelling precede the development of visible inflammation and structural organ damage in inflammatory rheumatic diseases such as the inflammatory arthritides. As such, visualising and measuring metabolic tissue activity could be useful to identify biomarkers of disease activity already in a very early phase. Recent advances in imaging have led to the development of so-called 'metabolic imaging' tools that can detect these changes in metabolism in an increasingly accurate manner and non-invasively.Nuclear imaging techniques such as F-D-glucose and fibroblast activation protein inhibitor-labelled positron emission tomography are increasingly used and have yielded impressing results in the visualisation (including whole-body staging) of inflammatory changes in both early and established arthritis. Furthermore, optical imaging-based bedside techniques such as multispectral optoacoustic tomography and fluorescence optical imaging are advancing our understanding of arthritis by identifying intra-articular metabolic changes that correlate with the onset of inflammation with high precision and without the need of ionising radiation.Metabolic imaging holds great potential for improving the management of patients with inflammatory arthritis by contributing to early disease interception and improving diagnostic accuracy, thereby paving the way for a more personalised approach to therapy strategies including preventive strategies. In this narrative review, we discuss state-of-the-art metabolic imaging methods used in the assessment of arthritis and inflammation, and we advocate for more extensive research endeavours to elucidate their full field of application in rheumatology.
Topics: Humans; Arthritis; Inflammation; Tomography, X-Ray Computed; Positron-Emission Tomography; Molecular Imaging
PubMed: 38341194
DOI: 10.1136/rmdopen-2023-003880 -
Aging Clinical and Experimental Research Jul 2023Normal bone remodeling depends of a balance between bone forming cells, osteoblasts and bone resorbing cells, the osteoclasts. In chronic arthritides and some... (Review)
Review
Normal bone remodeling depends of a balance between bone forming cells, osteoblasts and bone resorbing cells, the osteoclasts. In chronic arthritides and some inflammatory and autoimmune diseases such as rheumatoid arthritis, there is a great constellation of cytokines produced by pannus that impair bone formation and stimulate bone resorption by inducing osteoclast differentiation and inhibiting osteoblast maturation. Patients with chronic inflammation have multiple causes that lead to low bone mineral density, osteoporosis and a high risk of fracture including circulating cytokines, impaired mobility, chronic administration of glucocorticoids, low vitamin D levels and post-menopausal status in women, among others. Biologic agents and other therapeutic measures to reach prompt remission might ameliorate these deleterious effects. In many cases, bone acting agents need to be added to conventional treatment to reduce the risk of fractures and to preserve articular integrity and independency for daily living activities. A limited number of studies related to fractures in chronic arthritides were published, and future investigation is needed to determine the risk of fractures and the protective effects of different treatments to reduce this risk.
Topics: Humans; Female; Arthritis, Rheumatoid; Osteoclasts; Bone Resorption; Bone and Bones; Osteoblasts; Cytokines; Fractures, Bone
PubMed: 37222927
DOI: 10.1007/s40520-023-02432-9 -
Zhejiang Da Xue Xue Bao. Yi Xue Ban =... Apr 2023Interleukin (IL)-36 is a family of cytokines that belongs to the larger IL-1 superfamily. IL-36 agonist/antagonist binds to the interleukin-36 receptor involving in... (Review)
Review
Interleukin (IL)-36 is a family of cytokines that belongs to the larger IL-1 superfamily. IL-36 agonist/antagonist binds to the interleukin-36 receptor involving in physiological inflammation regulation and pathogenesis of many inflammatory diseases. In inflammatory joint diseases, the expression of IL-36 changes, and some studies have initially explored the role of IL-36 in these diseases. In psoriatic arthritis, IL-36 signal mediates plasma cell and fibroblast-like synoviocyte crosstalk presenting IL-36 agonist/antagonist imbalance. In rheumatoid arthritis, IL-36 agonists induce fibroblast-like synoviocyte to produce pro-inflammatory factors, while IL-36 antagonist deficiency leads to lesion progression. In osteoarthritis, IL-36 agonists induce chondrocytes to produce catabolic enzymes and pro-inflammatory factors. This article reviews the expression and function of IL-36 in different inflammatory joint diseases to provide a reference for revealing their pathogenic mechanisms and discovering therapeutic targets.
Topics: Humans; Interleukins; Arthritis, Rheumatoid; Osteoarthritis; Arthritis, Psoriatic; Cytokines
PubMed: 37283111
DOI: 10.3724/zdxbyxb-2023-0034 -
Translational Research : the Journal of... Jun 2021Patients with inflammatory arthritis represent a possible high-risk group to COVID-19 due to their immunosuppressive regimen designed to maintain low disease activity.... (Review)
Review
Patients with inflammatory arthritis represent a possible high-risk group to COVID-19 due to their immunosuppressive regimen designed to maintain low disease activity. Thus, substantial effort has been put forth to understand the impact of COVID-19 on these patients. Patients with rheumatic diseases as a whole do not appear to be more susceptible to acquiring COVID-19. Furthermore, immunosuppression generally did not increase the likelihood of developing severe COVID-19, with the important exception of medium and high-dose glucocorticoid use. In addition, a small number of COVID-19 patients have developed new inflammatory arthritis; whether this represents an unmasking of previous subclinical disease or a bone fide virus-induced arthritis is unclear. Nevertheless, it appears that inflammatory arthritis patients currently on immunosuppression should continue their medication to prevent future flares and limit glucocorticoid usage. While this continues to be a rapidly evolving field, these data are reassuring to both patients with and providers treating inflammatory arthritides.
Topics: Arthritis; COVID-19; Humans; Immunosuppressive Agents; Rheumatic Diseases; SARS-CoV-2; Severity of Illness Index
PubMed: 33626415
DOI: 10.1016/j.trsl.2021.02.010 -
Frontiers in Immunology 2023The NLRP3 inflammasome, which belongs to the pyrin domain containing 3 family of NOD-like receptors, has a significant impact on both the innate and adaptive immune... (Review)
Review
The NLRP3 inflammasome, which belongs to the pyrin domain containing 3 family of NOD-like receptors, has a significant impact on both the innate and adaptive immune responses. Regulating host immune function and protecting against microbial invasion and cell damage, the NLRP3 inflammasome plays a crucial role. By triggering caspase-1, it facilitates the development of the inflammatory cytokines IL-1β and IL-18, and triggers cell pyroptosis, resulting in cell lysis and demise. Common sterile arthritis includes osteoarthritis (OA), rheumatoid arthritis (RA) and gouty arthritis (GA), all of which manifest as bone destruction and synovial inflammation in a complex inflammatory state, placing a significant medical burden on the families of patients and government agencies. In the past few years, there has been a growing interest in investigating the impact of cell pyroptosis on arthritis development, particularly the widespread occurrence of pyroptosis mediated by the NLRP3 inflammasome. The NLRP3 inflammasome's biological properties are briefly described in this review, along with the presentation of the fundamental processes of pyroptosis resulting from its activation. Furthermore, we provide a summary of the advancements made in studying the NLRP3 inflammasome in various forms of arthritis and enumerate the intervention approaches that target the NLRP3-mediated pyroptosis, either directly or indirectly. These discoveries lay the groundwork for future investigations on medications for arthritis, offering fresh approaches for the clinical identification and treatment of this condition.
Topics: Humans; Inflammasomes; NLR Family, Pyrin Domain-Containing 3 Protein; Arthritis, Rheumatoid; Osteoarthritis; Arthritis, Gouty
PubMed: 37954594
DOI: 10.3389/fimmu.2023.1273174 -
JBJS Reviews Aug 2021Orthopaedics pioneered the expansion of gene therapy beyond its traditional scope of diseases that are caused by rare single-gene defects. Orthopaedic applications of...
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Orthopaedics pioneered the expansion of gene therapy beyond its traditional scope of diseases that are caused by rare single-gene defects. Orthopaedic applications of gene therapy are most developed in the areas of arthritis and regenerative medicine, but several additional possibilities exist.
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Invossa, an ex vivo gene therapeutic for osteoarthritis, was approved in South Korea in 2017, but its approval was retracted in 2019 and remains under appeal; a Phase-III clinical trial of Invossa has restarted in the U.S.
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There are several additional clinical trials for osteoarthritis and rheumatoid arthritis that could lead to approved gene therapeutics for arthritis.
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Bone-healing and cartilage repair are additional areas that are attracting considerable research; intervertebral disc degeneration and the healing of ligaments, tendons, and menisci are other applications of interest. Orthopaedic tumors, genetic diseases, and aseptic loosening are additional potential targets.
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If successful, these endeavors will expand the scope of gene therapy from providing expensive medicines for a few patients to providing affordable medicines for many.
Topics: Arthritis, Rheumatoid; Genetic Therapy; Humans; Intervertebral Disc Degeneration; Orthopedics; Osteoarthritis
PubMed: 34437305
DOI: 10.2106/JBJS.RVW.20.00220 -
Frontiers in Immunology 2021Inflammasome is a cytoplasmic multiprotein complex that facilitates the clearance of exogenous microorganisms or the recognition of endogenous danger signals, which is... (Review)
Review
Inflammasome is a cytoplasmic multiprotein complex that facilitates the clearance of exogenous microorganisms or the recognition of endogenous danger signals, which is critically involved in innate inflammatory response. Excessive or abnormal activation of inflammasomes has been shown to contribute to the development of various diseases including autoimmune diseases, neurodegenerative changes, and cancers. Rheumatoid arthritis (RA) is a chronic and complex autoimmune disease, in which inflammasome activation plays a pivotal role in immune dysregulation and joint inflammation. This review summarizes recent findings on inflammasome activation and its effector mechanisms in the pathogenesis of RA and potential development of therapeutic targeting of inflammasome for the immunotherapy of RA.
Topics: Animals; Arthritis, Rheumatoid; Autoimmunity; Biomarkers; Disease Management; Disease Susceptibility; Genetic Predisposition to Disease; Humans; Inflammasomes; Molecular Targeted Therapy; Polymorphism, Single Nucleotide
PubMed: 35095918
DOI: 10.3389/fimmu.2021.816839 -
Trends in Biotechnology Apr 2023Disorders of the synovial joint, such as osteoarthritis (OA) and rheumatoid arthritis (RA), afflict a substantial proportion of the global population. However, current... (Review)
Review
Disorders of the synovial joint, such as osteoarthritis (OA) and rheumatoid arthritis (RA), afflict a substantial proportion of the global population. However, current clinical management has not been focused on fully restoring the native function of joints. Organ-on-chip (OoC), also called a microphysiological system, which typically accommodates multiple human cell-derived tissues/organs under physiological culture conditions, is an emerging platform that potentially overcomes the limitations of current models in developing therapeutics. Herein, we review major steps in the generation of OoCs for studying arthritis, discuss the challenges faced when these novel platforms enter the next phase of development and application, and present the potential for OoC technology to investigate the pathogenesis of joint diseases and the development of efficacious therapies.
Topics: Humans; Arthritis, Rheumatoid; Osteoarthritis; Microphysiological Systems
PubMed: 35995600
DOI: 10.1016/j.tibtech.2022.07.011 -
Cells Aug 2019Arthritis is inflammation of the joints accompanied by osteochondral destruction. It can take many forms, including osteoarthritis, rheumatoid arthritis, and psoriatic... (Review)
Review
Arthritis is inflammation of the joints accompanied by osteochondral destruction. It can take many forms, including osteoarthritis, rheumatoid arthritis, and psoriatic arthritis. These diseases share one commonality-osteochondral destruction based on inflammation. The background includes a close interaction between osseous tissues and immune cells through various inflammatory cytokines. However, the tissues and cytokines that play major roles are different in each disease, and as a result, the mechanism of osteochondral destruction also differs. In recent years, there have been many findings regarding not only extracellular signaling pathways but also intracellular signaling pathways. In particular, we anticipate that the intracellular signals of osteoclasts, which play a central role in bone destruction, will become novel therapeutic targets. In this review, we have summarized the pathology of arthritis and the latest findings on the mechanism of osteochondral destruction, as well as present and future therapeutic strategies for these targets.
Topics: Arthritis; Bone Resorption; Bone and Bones; Cartilage; Cytokines; Humans; Inflammation; Osteoclasts; Signal Transduction
PubMed: 31382539
DOI: 10.3390/cells8080818