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      Matrix metalloproteinase-13, NF-κB p65 and interleukin-1β are associated with the severity of knee osteoarthritis

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          Abstract

          Knee osteoarthritis (KOA) is a prevalent disease, especially in the elderly. The present study examined the expression of matrix metalloproteinase-13 (MMP-13), NF-κBp65 and interleukin (IL)-lβ in the synovial tissues of KOA patients and the role of MMP-13 and the NF-κBp65 signalling pathway in KOA pathogenesis. A total of 100 KOA patients were enrolled in our hospital from December 2015 to December 2017 and were classified into either a mild KOA group (Outerbridge grade 1 and 2) or a severe KOA group (Outerbridge grade 3 and 4). Non-OA patients were included as controls. Synovial tissues from patients in both groups were collected for detection of the mRNA and protein expression of MMP-13, NF-κBp65 and IL-lβ. Synovial tissue slices were subjected to haematoxylin and eosin staining and immunohistochemistry (SP method). Cartilage tissues were observed under a light microscope after Safranin O-fast green staining. Reverse transcription-quantitative PCR and western blot analyses demonstrated that the expression of MMP-13, NF-κBp65 and IL-lβ in the mild and severe groups were substantially upregulated compared with the control group (all P<0.05). A positive correlation between MMP-13 and NF-κBp65 expression in the KOA synovial tissues was identified (P<0.05). Immunohistochemistry revealed that the expression of MMP-13 and NF-κBp65 was related to the severity of KOA (MMP-13: severe, 92.54%; moderate, 76.52%; control: 32.14%; and NF-κBp65: severe, 85.56%; moderate, 48.12%; control: 28.32%). This evidence indicated that the severity of KOA was related to MMP-13 and NF-κBp65 expression. The NF-κB signalling pathway may be activated during OA progression, which could upregulate the expression of MMP-13 and IL-1β and accelerate the deterioration of articular cartilage.

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          Knee extensor muscle weakness is a risk factor for development of knee osteoarthritis. A systematic review and meta-analysis.

          The objective of this study was to perform a systematic review and meta-analysis on the association between knee extensor muscle weakness and the risk of developing knee osteoarthritis. A systematic review and meta-analysis was conducted with literature searches in Medline, SPORTDiscus, EMBASE, CINAHL, and AMED. Eligible studies had to include participants with no radiographic or symptomatic knee osteoarthritis at baseline; have a follow-up time of a minimum of 2 years, and include a measure of knee extensor muscle strength. Hierarchies for extracting data on knee osteoarthritis and knee extensor muscle strength were defined prior to data extraction. Meta-analysis was applied on the basis of the odds ratios (ORs) of developing symptomatic knee osteoarthritis or radiographic knee osteoarthritis in subjects with knee extensor muscle weakness. ORs for knee osteoarthritis and 95% confidence intervals (CI) were estimated and combined using a random effects model. Twelve studies were eligible for inclusion in the meta-analysis after the initial searches. Five cohort studies with a follow-up time between 2.5 and 14 years, and a total number of 5707 participants (3553 males and 2154 females), were finally included. The meta-analysis showed an overall increased risk of developing symptomatic knee osteoarthritis in participants with knee extensor muscle weakness (OR 1.65 95% CI 1.23, 2.21; I(2) = 50.5%). This systematic review and meta-analysis showed that knee extensor muscle weakness was associated with an increased risk of developing knee osteoarthritis in both men and women.
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            Evidence for central sensitization in patients with osteoarthritis pain: a systematic literature review.

            Hyperexcitability of the central nervous system (CNS) has been suggested to play an important role in the chronic pain experienced by osteoarthritis (OA) patients. A systematic review following PRISMA guidelines was performed to evaluate the existing evidence from the literature related to the presence of central sensitization (CS) in patients with OA.Electronic databases PubMed and Web of Science were searched to identify relevant articles using pre-defined keywords regarding CS and OA. Full-text clinical reports addressing studies of CS in human adults with chronic complaints due to osteoarthritis were included and screened for methodological quality by two independent reviewers. From the 40 articles that were initially eligible for methodological quality assessment, 36 articles achieved sufficient scores and therefore were discussed. The majority of these studies were case-control studies and addressed OA of the knee joint. Different subjective and objective parameters considered manifestations of CS, which have been previously reported in other chronic pain conditions such as whiplash or rheumatoid arthritis, were established in subjects with OA pain. Overall results suggest that, although peripheral mechanisms are involved in OA pain, hypersensitivity of the CNS plays a significant role in a subgroup of subjects within this population. Although the majority of the literature provides evidence for the presence of CS in chronic OA pain, clinical identification and treatment of CS in OA is still in its infancy, and future studies with good methodological quality are necessary.
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              Homeostatic mechanisms in articular cartilage and role of inflammation in osteoarthritis.

              Osteoarthritis (OA) is a whole joint disease, in which thinning and disappearance of cartilage is a critical determinant in OA progression. The rupture of cartilage homeostasis whatever its cause (aging, genetic predisposition, trauma or metabolic disorder) induces profound phenotypic modifications of chondrocytes, which then promote the synthesis of a subset of factors that induce cartilage damage and target other joint tissues. Interestingly, among these factors are numerous components of the inflammatory pathways. Chondrocytes produce cytokines, chemokines, alarmins, prostanoids, and adipokines and express numerous cell surface receptors for cytokines and chemokines, as well as Toll-like receptors. These receptors activate intracellular signaling pathways involved in inflammatory and stress responses of chondrocytes in OA joints. This review focuses on mechanisms responsible for the maintenance of cartilage homeostasis and highlights the role of inflammatory processes in OA progression.
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                Author and article information

                Journal
                Exp Ther Med
                Exp Ther Med
                ETM
                Experimental and Therapeutic Medicine
                D.A. Spandidos
                1792-0981
                1792-1015
                June 2020
                20 March 2020
                20 March 2020
                : 19
                : 6
                : 3620-3626
                Affiliations
                Department of Orthopedics, Nanjing Luhe People's Hospital, Nanjing, Jiangsu 211500, P.R. China
                Author notes
                Correspondence to: Dr Fu-Qing Lin, Department of Orthopedics, Nanjing Luhe People's Hospital, 28 Yan'an Road, Luhe, Nanjing, Jiangsu 211500, P.R. China linfuqing18@ 123456163.com
                Article
                ETM-0-0-8618
                10.3892/etm.2020.8618
                7185070
                32346426
                7dc9ba82-5602-4fd4-90d5-6c8104859852
                Copyright: © Zhao et al.

                This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.

                History
                : 14 October 2018
                : 30 October 2019
                Categories
                Articles

                Medicine
                knee osteoarthritis,matrix metalloproteinase-13,nf-κb p65,interleukin-1β,nf-κb signalling pathway

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