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Osteoarthritis (OA) is a frequent musculoskeletal disorder affecting millions of people worldwide. Despite advances in understanding the pathogenesis of OA, prognostic biomarkers or effective targeted treatment are not currently available. Research on epigenetic factors has yielded some new insights as new technologies for their detection continue to emerge. In this context, non-coding RNAs, including microRNAs, long non-coding RNAs, circular RNAs, piwi-interacting RNAs, and small nucleolar RNAs, regulate intracellular signaling pathways and biological processes that have a crucial role in the development of several diseases. In this review, we present current knowledge on the role of epigenetic factors with a focus on non-coding RNAs in the development, prediction and treatment of OA. This article is categorized under: RNA in Disease and Development > RNA in Disease., (© 2022 Wiley Periodicals LLC.) more...

Background: Osteoarthritis (OA) is a common degenerative joint condition caused by an imbalance between cartilage synthesis and degradation, which disrupts joint homeostasis. This study investigated the anti-inflammatory and joint-improving effects of Pinus densiflora root extract powder (PDREP) in both in vitro and in vivo OA models. Methods/Results: In an in vitro OA model, in which SW1353 human chondrosarcoma cells were treated with interleukin (IL)-1β, PDREP treatment significantly reduced the mRNA levels of matrix metalloproteinase (MMP)-1, MMP-3, and MMP-13 while enhancing collagen type II alpha 1 (Col2a1) mRNA level, and decreased IL-6 and prostaglandin E2 (PGE2) levels. In addition, PDREP inhibited the phosphorylation of extracellular signal-regulated kinases (ERK), c-Jun N-terminal kinase (JNK), p38, nuclear factor-kappa B (NF-κB), and the expression of inducible nitric oxide synthase (iNOS). In a monosodium iodoacetate (MIA)-induced OA rat model, the administration of PDREP resulted in decreased OA clinical indices, improved weight-bearing indices and gait patterns, reduced histological damage, and lowered serum inflammatory cytokine and MMPs expression. Furthermore, PDREP downregulated the phosphorylation of ERK, JNK, p38, and NF-κB, as well as the expression of iNOS, consistent with the in vitro findings. Conclusions: These results suggest that PDREP exhibits anti-inflammatory and joint-improving effects and has potential as a therapeutic strategy or functional food for the treatment of OA. [ABSTRACT FROM AUTHOR] more...

Arthritides are a highly heterogeneous group of disorders that include two major clinical entities, localized joint disorders such as osteoarthritis (OA) and systemic autoimmune-driven diseases such as rheumatoid arthritis (RA). Arthritides are characterized by chronic debilitating musculoskeletal conditions and systemic chronic inflammation. Poor mental health is also one of the most common comorbidities of arthritides. Depressive symptoms which are most prevalent, negatively impact patient global assessment diminishing the probability of achieving the target of clinical remission. Here, we investigated new insights into mechanisms that link different joint disorders to poor mental health, and to this issue, we explored the action of the synovial fluid-derived extracellular vesicles (EVs) on neuronal function. Our data show that the exposure of neurons to different concentrations of EVs derived from both RA and OA synovial fluids (RA-EVs and OA-EVs) leads to increased excitatory synaptic transmission but acts on specific modifications on excitatory or inhibitory synapses, as evidenced by electrophysiological and confocal experiments carried out in hippocampal cultures. The treatment of neurons with EVs membrane is also responsible for generating similar effects to those found with intact EVs suggesting that changes in neuronal ability arise upon EVs membrane molecules′ interactions with neurons. In humans with arthritides, we found that nearly half of patients (37.5%) showed clinically significant psychiatric symptoms (CGIs score ≥ 3), and at least mild anxiety (HAM-A ≥ 7) or depression (MADRS and HAM-D ≥ 7); interestingly, these individuals revealed an increased concentration of synovial EVs. In conclusion, our data showing opposite changes at the excitatory and inhibitory levels in neurons treated with OA- and RA-EVs, lay the scientific basis for personalized medicine in OA and RA patients, and identify EVs as new potential actionable biomarkers in patients with OA/RA with poor mental health. [ABSTRACT FROM AUTHOR] more...

Matrix metalloproteinases (MMPs) play crucial roles in tissue homeostasis and pathologies by remodeling the extracellular matrix. Previous studies have demonstrated the biological activities of MMP-derived cleavage products. Furthermore, specific fragments can serve as biomarkers. Therefore, an in vitro cleavage assay to identify substrates and characterize cleavage patterns could provide important insight in disease-relevant mechanisms and the identification of novel biomarkers. In the pathogenesis of osteoarthritis (OA), MMP-2, -8, -9 and -13 are of vital importance. However, it is unclear which protease can cleave which matrix component. To address this question, we established an in vitro cleavage assay using recombinantly expressed MMPs and the two cartilage matrix components, COMP and thrombospondin-4. We found a time- and concentration-dependent degradation and an MMP-specific cleavage pattern for both proteins. Cleavage products can now be enriched and purified to investigate their biological activity. To verify the in vivo relevance, we compared the in vitro cleavage patterns with serum and synovial fluid from OA patients and could indeed detect fragments of similar size in the human samples. The cleavage assay can be adapted to other MMPs and substrates, making it a valuable tool for many research fields. [ABSTRACT FROM AUTHOR] more...

Objectives: This study aims to define serum levels of netrin-1 and netrin receptors in patients with fibromyalgia (FM) and osteoarthritis (OA). Patients and methods: This cross-sectional study was conducted with a total of 150 female participants (mean age: 47.2±16.1 years; range, 18 to 89 years) at Fırat University between June 2016 and December 2016. The participants were evaluated in three groups: the FM group with 50 patients, the OA group with 50 patients, and the control group, which included 50 healthy volunteers. Netrin-1, netrin receptors (DCC, UNC5B, and UNC5D), interleukin (IL)-6, IL-10, and IL-17 levels were analyzed by the enzyme-linked immunosorbent assay from the serum samples of the participants. Results: The level of serum netrin-1 was significantly lower in the FM group than in the control and OA groups (p<0.01 and p<0.001, respectively). However, the difference between patients with OA and healthy controls in terms of netrin-1 was not statistically significant (p>0.05). In addition, serum levels of netrin receptors and cytokines in the FM group were similar to the control group (p>0.05). However, serum DCC, UNC5D, IL-6, and IL-10 levels were higher in the OA group compared to the control group (p<0.001, p<0.05, p<0.01, and p<0.001, respectively). Conclusion: Serum netrin-1 level is suppressed in FM, which suggests that netrin-1 is influential in FM pathogenesis. [ABSTRACT FROM AUTHOR] more...

Osteoarthritis is considered a degenerative disease, with knee and hip osteoarthritis being the most common form. Drug treatment is aimed at relieving symptoms with analgesics and non-selective or selective NSAIDs. Curcuma longa is a species used in Ayurvedic medicine without treating inflammatory conditions. The purpose of this scoping review is to identify and examine the evidence related to the effects of using C. longa in the treatment of osteoarthritis and the possible benefits in relation to treatment with NSAIDs. This research was conducted using an approach proposed by Arksey and O'Malley, the JBI Scope Review Methodology Handbook, and the PRISMA-ScR Guidelines and Checklist. Four studies meet the inclusion criteria, three were obtained as trials randomized clinical trials and the fourth study is a pilot clinical trial. The evidence raised shows that treatment with C. longa can reduce the symptoms of osteoarthritis with less potential to cause adverse events. However, the methodological quality of the included studies and the sample size do not allow definitive selections to be taken. These limitations indicate the need to carry out randomized clinical trials of high methodological quality, following CONSORT guidelines to confirm the efficacy of C. longa in the treatment of osteoarthritis and its benefits over conventional treatments. [ABSTRACT FROM AUTHOR] more...

Copyright of Hungarian Medical Journal / Orvosi Hetilap is the property of Akademiai Kiado and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.) more...

Aim: Mesenchymal stem cell (MSC)‐based therapy is being explored in treating osteoarthritis (OA). Human umbilical cord‐derived mesenchymal stem cells (hUC‐MSCs) are least reported. In this study, we investigated the effects of single intra‐articular injections of hUC‐MSCs on a rat OA model. Method: hUC‐MSCs were isolated from the Wharton's jelly of the human umbilical cord and identified. Eighteen Sprague‐Dawley rats were used for the OA model. All rats were divided into 3 groups: hyaluronic acid (HA)+MSCs (n = 6), HA (n = 6), and control group (n = 6). One by 106 hUC‐MSCs in 100 μL HA, 100 μL HA or 100 μL saline were injected into the knee joint 4 weeks post‐surgery as a single dose. Cartilage degeneration was evaluated at 6 and 12 weeks after treatment with macroscopic examination, micro‐computed tomography analysis, behavioral analysis, and histology. Results: At 6 weeks, the HA + MSCs group had a significantly better International Cartilage Repair Society score in the femoral condyle compared to the HA and control groups. Histological analysis also showed more proteoglycan and less cartilage loss, with lower modified Mankin score in the HA + MSCs group. However, at 12 weeks there were no significant differences between groups from macroscopic examination and histological analysis. Subchondral bone sclerosis of the medial femoral condyle and behavioral tests showed no significant differences between groups at 6 and 12 weeks. Conclusion: These findings indicate that single injection of hUC‐MSCs can have temporary effects on decelerating the progression of cartilage degeneration in OA rats, but may not inhibit OA progression in the long‐term. [ABSTRACT FROM AUTHOR] more...

Objective: To identify long noncoding RNAs (lncRNAs) associated with the inflammatory phenotype of synovial fibroblasts from obese patients with osteoarthritis (OA), and to explore the expression and function of these lncRNAs. Methods: Synovium was collected from normal‐weight patients with hip fracture (non‐OA; n = 6) and from normal‐weight (n = 8) and obese (n = 8) patients with hip OA. Expression of RNA was determined by RNA‐sequencing and quantitative reverse transcription–polymerase chain reaction. Knockdown of lncRNA was performed using LNA‐based GapmeRs. Synovial fibroblast cytokine production was measured by enzyme‐linked immunosorbent assay. Results: Synovial fibroblasts from obese patients with OA secreted greater levels of interleukin‐6 (IL‐6) (mean ± SEM 162 ± 21 pg/ml; P < 0.001) and CXCL8 (262 ± 67 pg/ml; P < 0.05) compared to fibroblasts from normal‐weight patients with OA (IL‐6, 51 ± 4 pg/ml; CXCL8, 78 ± 11 pg/ml) or non‐OA patients (IL‐6, 35 ± 3 pg/ml; CXCL8, 56 ± 6 pg/ml) (n = 6 patients per group). RNA‐sequencing revealed that fibroblasts from obese OA patients exhibited an inflammatory transcriptome, with increased expression of proinflammatory messenger RNAs (mRNAs) as compared to that in fibroblasts from normal‐weight OA or non‐OA patients (>2‐fold change, P < 0.05; n = 4 patients per group). A total of 19 lncRNAs were differentially expressed between normal‐weight OA and non‐OA patient fibroblasts, and a further 19 lncRNAs were differentially expressed in fibroblasts from obese OA patients compared to normal‐weight OA patients (>2‐fold change, P < 0.05 for each), which included the lncRNA for metastasis‐associated lung adenocarcinoma transcript 1 (MALAT1). MALAT1 was rapidly induced upon stimulation of OA synovial fibroblasts with proinflammatory cytokines, and was up‐regulated in the synovium from obese OA patients as compared to normal‐weight OA patients (1.6‐fold change, P < 0.001) or non‐OA patients (6‐fold change, P < 0.001). MALAT1 knockdown in OA synovial fibroblasts (n = 4 patients) decreased the levels of mRNA expression and protein secretion of CXCL8 (>1.5‐fold change, P < 0.01), whereas it increased expression of mRNAs for TRIM6 (>2‐fold change, P < 0.01), IL7R (<2‐fold change, P < 0.01), HIST1H1C (>1.5‐fold change, P < 0.001), and MAML3 (>1.5‐fold change, P < 0.001). In addition, MALAT1 knockdown inhibited the proliferation of synovial fibroblasts from obese patients with OA. Conclusion: Synovial fibroblasts from obese patients with hip OA exhibit an inflammatory phenotype. MALAT1 lncRNA may mediate joint inflammation in obese OA patients. [ABSTRACT FROM AUTHOR] more...

Objective: The aim of this study was to investigate cross-sectional associations between serum levels of IL-8 and the above outcomes in patients with knee osteoarthritis (OA). Methods: A total of 160 subjects with clinical knee OA were included. Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score and Lequesne index were used to assess the joint symptom. Magnetic resonance imaging was used to measure knee structural abnormalities including infrapatellar fat pad (IPFP) signal intensity alternation. Knee radiographic OA was assessed by radiography using the Kellgren-Lawrence (K-L) grading system. Enzyme-linked immunosorbent assay was used to measure the serum levels of IL-8 and cartilage or bone biomarkers. Results: In multivariable analyses, serum IL-8 was positively associated with WOMAC weight-bearing pain (β 2.85, P = 0.028), WOMAC physical dysfunction (β 12.71, P = 0.048), and Lequesne index (β 1.65, P = 0.015), and had positive associations with IPFP signal intensity alteration (OR 3.18, P = 0.011) and serum levels of N-telopeptide of type I collagen (NTXI), N-terminal procollagen III propeptide (PIIINP), matrix metalloproteinase (MMP)3, and MMP13 (β 0.24–1.44, all P < 0.05) in patients with clinical knee OA. Furthermore, there were positive associations between IL-8 and WOMAC score (β 22.49, P = 0.037), K-L grades (OR 3.88, P = 0.013), and IPFP signal intensity alteration (OR 3.20, P = 0.033) in patients with radiographic OA. Conclusions: Serum levels of IL-8 were positively associated with increased knee symptoms, IPFP signal intensity alteration, and serum levels of bone and/or cartilage biomarkers, suggesting that IL-8 may have a role to play in knee OA. Key Point • This study systemically investigates the associations between serum IL 8 and knee symptoms, joint structures, and cartilage or bone biomarkers in patients with knee osteoarthritis, and some significant associations have been found, suggesting that IL 8 may have a role to play in knee OA. [ABSTRACT FROM AUTHOR] more...

Background: Previously, we reported that ChondorT showed significant anti-arthritis and anti-inflammatory effects. ChondroT, a new herbal medication, consists of the water extracts of Osterici Radix, Lonicerae Folium, Angelicae Gigantis Radix, Clematidis Radix, and Phellodendri Cortex (6:4:4:4:3). The objective of this study was to investigate the effects of ChondroT in collagenase-induced osteoarthritis rat model. Methods: Osteoarthritis was induced by the injection of collagenase into the right knee joint cavity of rats. The samples were divided into seven groups [intact (n = 6), control (n = 6), indomethacin (n = 6), Joins tab (n = 6), ChondroT50 (n = 6), ChondroT100 (n = 6), and ChondroT200 (n = 6)]. The control group was administered normal saline, indomethacin group was administered indomethacin (2 mg/kg), and Joins tab group was administered Joins Tab (20 mg/kg). The ChondroT50, ChondroT100, and ChondroT200 groups were administered 50, 100, and 200 mg/kg of ChondroT, respectively. All oral administrations were initiated 7 days after the induction of arthritis and were continued for a total of 12 days. At the end of the experiment, serum aminotransferase, albumin, blood urea nitrogen, creatinine, leukocyte, and inflammatory cytokines [tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-6] were analyzed. Hematoxylin and eosin (H&E) and safranin O-fast green staining of the articular structures of the knee joint were performed. Results: TNF-α and IL-1β decreased in the ChondroT100 and ChondroT200 groups compared with those in the control group. IL-6 and aspartate aminotransferase decreased in the ChondroT50, ChondroT100, and ChondroT200 groups compared with that in the control group. Albumin, WBC and lymphocytes decreased in the ChondroT100 and ChondroT200 groups compared with those in the control group. In H&E stain, synoviocytes, cartilage lacunae, and chondrocytes were well preserved in the ChondroT100 and ChondroT200 groups, and safranin O-fast staining showed a clear reaction of proteoglycans in the ChondroT100 and ChondroT200 groups. Conclusions: Based on these results, it can be proposed that ChondroT has anti-osteoarthritic effects on collagenase-induced rat model. [ABSTRACT FROM AUTHOR] more...

Copyright of Shipin Kexue/ Food Science is the property of Food Science Editorial Department and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.) more...

Abstract: Aim: Osteoarthritis (OA) is a major cause of morbidity and incapacity in the elderly. This study evaluates serum levels of the chemokines CCL2, CXCL8, CXCL9, and CXCL10 in 16 patients with primary OA of the knees, and investigates how treatment with hydroxychloroquine (HCQ) for 4 months affects these chemokine levels. Method: Thirteen elderly patients received a placebo. Healthy control groups consisted of 10 elderly individuals (age > 60 years) with no clinical or radiological evidence of OA (CT‐O), and 10 young adult individuals, (CT‐Y group, age < 40 years). Results: The CT‐Y group presented lower levels of all chemokines studied, in comparison to the other groups. HCQ treatment did not alter the serum levels of CCL2 (P = 0.80), CXCL8 (P = 0.76), CXCL9 (P = 0.95) and CXCL10 (P = 0.74) in OA patients. Conclusion: Hydroxychloroquine treatment did not alter the serum levels of CCL2, CXCL8, CXCL9 or CXCL10 in patients with OA of the knees, although increased serum levels correlated with aging for all subjects, including controls. [ABSTRACT FROM AUTHOR] more...

Background: Joint impact injuries initiate a progressive articular damage finally leading to post-traumatic osteoarthritis (PTOA). Racehorses represent an ideal, naturally available, animal model of the disease. Standardbred racehorses developing traumatic osteoarthritis of the fetlock joint during the first year of their career were enrolled in our study. Age-matched controls were contemporarily included. Biomarker levels of equine osteoarthritis were measured in serum and synovial fluid (SF) at baseline, and repeated yearly over the next 4 years of training (from T1 to T4). The effect of time and disease on the biomarker concentrations were analysed, and their relationship with clinical and radiographic parameters were assessed. We hypothesized that the kinetics of pro-inflammatory cytokines and structural biomarkers of joint disease would demonstrate progression of degenerative joint status during post-traumatic osteoarthritis and clarify the effect of early joint trauma. Results: The concentrations of IL1-ß, IL-6, TNF-a in the SF of PTOA group peaked at T0, decreased at T1, and then progressively increased with time, reaching levels higher than those observed at baseline starting from T3. CTXII and COMP levels were similar in PTOA and control horses at baseline, and increased in serum and synovial fluid of PTOA horses starting from T2 (serum and synovial CTXII, and serum COMP) or T3 (synovial COMP). The percentual change of TNF-a in the SF of the affected joints independently contributed to explaining the radiological changes at T3 vs T2 and T4 vs T3. Conclusions: Temporal changes of selected biomarkers in STBRs with an acute episode of traumatic fetlock OA demonstrated that long-term increased concentrations of inflammatory cytokines, type II collagen fragments and COMP, in the SF and serum, are related to PTOA. Based on the observed decrease in inflammatory merkers at T1, we hypothesize that the progression of PTOA could be effectively modulated by proper treatment strategies. Annual variations of synovial concentration of TNF-a can reliably predict radiographic progression of PTOA. [ABSTRACT FROM AUTHOR] more...

Background: The purpose of this study is to investigate the possible attenuating role of the intra-articular administration of Fetuin-A in post-traumatic secondary osteoarthritis in rats, and also its effect on the systematic levels of interleukins (ILs)-2,4,7, bone morphogenetic proteins (BMPs) 2, 4, 7, C-Reactive Protein (CRP) and Fetuin-A. Methods: Thirty male Sprague Dawley rats were separated in two groups where post-traumatic osteoarthritis was induced surgically by Anterior Cruciate Ligament Transection and the transection of the Medial Collateral Ligament of the right knee. In the Control Group, only the surgical intervention took place. In Fetuin Group, along with the induction of osteoarthritis, a single dose of bovine fetuin was administrated intra-articularly, intra-operatively. Both groups were examined for 8 weeks. The levels of interleukins, bone morphogenetic proteins, Fetuin-A and C-Reactive Protein were evaluated by ELISA of peripheral blood in three time periods: preoperatively, 5 and 8 weeks post-operatively. Osteoarthritic lesions of the knee were classified according to the Osteoarthritis Research Society International Grading System and the Modified Mankin Score, by histologic examination. Results: IL-2 levels were significantly decreased in the Fetuin Group. No statistical difference was signed on the levels of IL-7, BMP-2,4,7 and Fetuin-A between the two groups. CRP levels were significantly increased in the Fetuin Group in 5 weeks of the experiment. Fetuin Group signed better scores according to the OARSI classification system and Modified Mankin Score, without any statistical significance. Conclusions: Intra-articular administration of Fetuin-A restrictively affected the progression of post-traumatic arthritis in rats, as only the levels of IL-2 were decreased as well as limited osteoarthritic lesions were observed on the Fetuin Group. [ABSTRACT FROM AUTHOR] more...

Osteoarthritis (OA) is characterized by degradation of the cartilage matrix, leading to pathologic changes in the joints. However, the pathogenic effects of synovial tissue inflammation on OA knees are not clear. To investigate whether the inflammation caused by the medial plica is involved in the pathogenesis of osteoarthritis, we examined the expression of matrix metalloproteinases (MMPs), tissue inhibitors of metalloproteinases (TIMPs), interleukin (IL)-1β, and tumor necrosis factor (TNF)-α in the medial plica and pannus-like tissue in the knees of patients with medial compartment OA who underwent either arthroscopic medial release (stage II; 15 knee joints from 15 patients) or total knee replacement (stage IV; 18 knee joints from 18 patients). MMP-2, MMP-3, MMP-9, IL-1β, and TNF-α mRNA and protein levels measured, respectively, by quantitative real-time PCR and Quantibody human MMP arrays, were highly expressed in extracts of medial plica and pannus-like tissue from stage IV knee joints. Immunohistochemical staining also demonstrated high expression of MMP-2, MMP-3, and MMP-9 in plica and pannus-like tissue of stage IV OA knees and not in normal cartilage. Some TIMP/MMP ratios decreased significantly in both medial plica and pannus-like tissue as disease progressed from stage II to stage IV. Furthermore, the migration of cells from the pannus-like tissue was enhanced by IL-1β, while plica cell migration was enhanced by TNF-α. The results suggest that medial plica and pannus-like tissue may be involved in the process of cartilage degradation in medial compartment OA of the knee. [ABSTRACT FROM AUTHOR] more...