Common Arthritic Disease Research Articles

HSF1 Increases EOGT-Mediated Glycosylation of Notch1 to Promote IL-1β-Induced Inflammatory Injury of Chondrocytes.

Osteoarthritis (OA) is the most common arthritic disease in humans. Nevertheless, the pathogenic mechanism of OA remains unclear. This study aimed to explore that heat-shock transcription factor 1 (HSF1) facilitated interleukin-1 beta (IL-1β) chondrocyte injury by increasing Notch1 O-linked N-acetylglucosamine (O-GlcNAc) modification level. Human chondrocytes were incubated with 5 ng/ml interleukin-1 beta (IL-1β) for 24 h to establish OA cell model. The messenger RNA (mRNA) or protein expressions were assessed using reverse transcription-quantitative polymerase chain reaction, western blot, or immunofluorescence. Chondrocyte viability was examined by Cell Counting Kit-8 assay. Enzyme-linked immunosorbent assay was employed to detect the secretion levels of interleukin-6 (IL-6) and interleukin-8 (IL-8). Immunoprecipitation was adopted to detect Notch1 O-GlcNAc modification level. The interaction between HSF1 and epidermal growth factor-like (EGF) domain-specific O-GlcNAc transferase (EOGT) promoter was analyzed by dual-luciferase reporter gene and chromatin immunoprecipitation assays. Herein, our results demonstrated that HSF1, EOGT, Notch1, and Notch1 intracellular domain (NICD1) expressions in chondrocytes were markedly increased by IL-1β stimulation. EOGT elevated Notch1 expression in IL-1β-treated chondrocytes by increasing Notch1 O-GlcNAc modification level. EOGT silencing reduced IL-1β-induced chondrocyte inflammatory injury. In addition, HSF1 knockdown relieved IL-1β-induced chondrocyte inflammatory injury. Molecular interaction experiment proved that HSF1 transcriptionally activated EOGT expression in IL-1β-treated chondrocytes. HSF1 promoted IL-1β-induced inflammatory injury in chondrocytes by increasing EOGT-mediated glycosylation of Notch1.

Identification of m7G-related hub biomarkers and m7G regulator expression pattern in immune landscape during the progression of osteoarthritis

BackgroundAccumulating evidence has shown that aberrant N7-methylguanosine (m7G) RNA methylation played an important role in the occurrence and development of cancer. However, knowledge of m7G modifications in inflammatory diseases is limited. Osteoarthritis (OA) is the most common arthritic disease with poor prognosis. Our research aimed to identify m7G-related hub biomarkers and investigate m7G regulator expression pattern in immune landscape of OA patients. MethodsGene expression profiles and their clinical information were obtained from the Gene Expression Omnibus (GEO) database, and differential analysis of 14 m7G-related regulators between elective OA and normal samples was performed. M7G-related hub genes for OA were mined based on single-sample gene set enrichment analysis (ssGSEA) and the random forest (RF) algorithm, and qRT-PCR was performed to confirm the abnormal expression of hub genes. Enrichment, protein–protein interaction (PPI), transcription factor (TF)-gene interaction and microRNA (miRNA)-gene coregulatory analysis based on m7G hub genes were performed. Then we predicted several candidate drugs related to m7G hub genes using DSigDB database. Moreover, we comprehensively evaluated m7G methylation patterns in OA samples and systematically correlated these modification patterns with the characteristics of immune cell infiltration. The m7G score was generated to quantify m7G methylation patterns for individual OA patients by the application of principal component analysis (PCA) algorithm. ResultsWe constructed an OA predictive model based on 4 m7G hub genes (SNUPN, METTL1, EIF4E2 and CYFIP1). Two m7G methylation patterns in OA were discovered to show distinct biological characteristics, and an m7G score were generated. M7G cluster A and a higher m7G score were found to be related to an inflamed phenotype. ConclusionsOur study was the first to comprehensively investigate the m7G methylation dysregulations in immune landscape during the progression of OA. These 4 m7G gene-related signatures can be used as novel OA biomarkers to predict the occurrence of OA. Evaluating the m7G methylation patterns of OA individuals will contribute to enhancing our cognition of immune infiltration characterization and guiding more effective immunotherapy strategies.

Early Results with the Use of Synthetic Cartilage Implant Augmented with 3D Printed Baseplate to Prevent Implant Subsidence for Treatment of Hallux Rigidus

Category: Midfoot/Forefoot Introduction/Purpose: Hallux rigidus (HR) of the first metatarsophalangeal joint (MTPJ) is a common arthritic disease which causes pain and stiffness. Synthetic cartilage implant (SCI) resurfacing has become a popular treatment option since it has similar biomechanical properties as native cartilage, reduces pain, and preserves MTPJ motion. However, recent studies have reported on implant subsidence leading to SCI treatment failure and subsequent revision surgery. A novel solution involves proximally inserting a custom 3D printed baseplate in the metatarsal head to prevent SCI subsidence. The purpose of this study is to evaluate the clinical and radiographic outcomes of patients who underwent SCI resurfacing augmented with a 3D printed beasplate for the treatment of HR by a single surgeon. Methods: Electronic health records were queried from August 2017 to August 2021 for patients who were treated with SCI (Cartiva Synthetic Cartilage Implant; Cartiva Inc., Alpharetta, GA) augmented with a custom 3D printed baseplate by a single surgeon. Through a dorsal approach to the MTPJ, the custom 3D printed baseplate is inserted in the metatarsal head and the SCI implant is positioned two millimeters proud from the cortex. An akin osteotomy is then performed and fixed with a staple. For the study, surgical indications included symptomatic HR and revision of previously failed SCI treatment. Patient demographics, body mass index (BMI), medical comorbidities, and followup periods were recorded. Preoperative and postoperative range of motion, visual analog scale (VAS) pain scores, and x-ray imaging were compared. Descriptive and univariate statistics were used to analyze data. Results: Twenty-one patients underwent SCI resurfacing augmented with a 3D printed baseplate. The cohort consisted of 18 females, and presented with a mean BMI of 30.4+-5 Kg/m2, mean age of 56.4+-10 years, and mean followup of 9.8+-13 months since the procedure. Patients experienced a significant improvement in VAS pain (P=0.002) scores. The SCI augmented with 3D printed baseplate survivorship was 90.4%, with only two (9.5%) patients requiring revision to first MTPJ arthrodesis for SCI subsidence and sesamoidal arthritis. Two (9.5%) patients additionally underwent reoperation for staple removal and infection. The first MTPJ space was maintained on x-ray imaging for 19 (90.5%) patients, with only two (9.5%) patients demonstrating implant subsidence. Conclusion: SCI resurfacing augmented with a custom 3D printed baseplate demonstrated significant improvements in pain and prevented implant subsidence in patients suffering from symptomatic HR. Future prospective studies should be performed to expand upon the clinical outcomes data analyzing this novel technique to prevent SCI subsidence in the treatment for HR.

Perioperative management of elderly patients with osteoarthritis requiring total knee arthroplasty.

Knee osteoarthritis is a common arthritic disease which mainly affects the elderly (≥65 years old) population. As a result of the cartilage degeneration, it can cause a significant amount of pain and functional limitation. In patients who are refractory to conservative management, total knee arthroplasty is being utilised as the last resort in management. In this review, we discuss the perioperative management of elderly patients with osteoarthritis requiring total knee arthroplasty.

Bioinformatics analysis of differentially expressed genes in subchondral bone in early experimental osteoarthritis using microarray data

BackgroundOsteoarthritis (OA) is the most common arthritic disease in humans, affecting the majority of individuals over 65 years of age. The aim of this study is to identify the gene expression profile specific to subchondral bone in OA by comparing the different expression profiles in experimental and sham-operation groups.MethodsGene expression profile GSE30322 was downloaded from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) were obtained by limma package. And Database for Annotation, Visualization and Integrated Discovery (DAVID) databases were further used to identify the potential gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. Furthermore, a protein–protein interaction (PPI) network was constructed and significant modules were extracted.ResultsTotally, 588 DEGs were identified including 199 upregulated DEGs and 389 downregulated DEGs screened in OA and sham-operation. GO showed that DEGs were significantly enhanced for ribosomal subunit export from nucleus and molting cycle. KEGG pathway analysis revealed that target genes were enriched in thiamine metabolism.ConclusionThese key candidate DEGs that affect the progression of OA, and these genes might serve as potential therapeutic targets for OA.

Urate transporter inhibitor lesinurad is a selective peroxisome proliferator-activated receptor gamma modulator (sPPAR\u03b3M) in vitro

Gout is the most common arthritic disease in human but was long neglected and therapeutic options are not satisfying. However, with the recent approval of the urate transporter inhibitor lesinurad, gout treatment has experienced a major innovation. Here we show that lesinurad possesses considerable modulatory potency on peroxisome proliferator-activated receptor γ (PPARγ). Since gout has a strong association with metabolic diseases such as type 2 diabetes, this side-activity appears as very valuable contributing factor to the clinical efficacy profile of lesinurad. Importantly, despite robustly activating PPARγ in vitro, lesinurad lacked adipogenic activity, which seems due to differential coactivator recruitment and is characterized as selective PPARγ modulator (sPPARγM).

Towards secondary prevention of early knee osteoarthritis

Osteoarthritis (OA) of the knee is the most common arthritic disease, yet a convincing drug treatment is not available. The current narrative review focuses on integration of scientific evidence and...

Protein biomarkers associated with pain mechanisms in osteoarthritis

Osteoarthritis (OA) is the most common arthritic disease in the world, leading to debilitating pain and destruction of joint tissues. While pain is the hallmark symptom of osteoarthritis, clear associations between pain and disease processes involved in joint deterioration are lacking. OA pain is multifactorial and may arise from multiple distinct or concurrent mechanisms, and may thus present as different pain sub-types. Several biomarkers developed to reflect important pathological processes are available, and associations between such biomarkers and OA pain may give hints to important pathological features, which have not been possible to assess using clinical, radiographic or magnetic resonance imaging techniques. This review highlights a selection of important, protein-derived biomarkers measured in body fluids from OA patients, which have been associated with different types and aspects of OA pain, and discusses the potential mechanisms behind the associations. SignificanceOsteoarthritis (OA) is a heterogenous disease affecting the entire joint, including cartilage, bone and synovium. While pain is the hallmark symptom of osteoarthritis, clear associations between pain and disease processes involved in joint deterioration are lacking. Thus, there is clear need for biomarkers that can accurately describe the underlying processes and distinguish between different disease and pain pathologies. In this review we discuss a selected number of biomarkers which have been directly or indirectly associated with pain mechanisms and development of pain in OA either via structural correlates or as molecular sensitizing agents. We further evaluate the challenges that the OA field faces in the development and application of biomarkers for OA pain.

Assessing the Quality and Content of Accessible Information on the Internet Regarding Hallux Rigidus

Category: Midfoot/Forefoot Introduction/Purpose: The internet has grown into one of the biggest resource of easy accessible health information for the general public. Hallux rigidus (HR) is the most common arthritic disease pattern of the foot. There is no mutual consent on the ideal operative intervention for this disease. State of knowledge is essential for a decision to proceed with a HR specific treatment, since this decision is ultimately a shared one between the patient and the physician. Therefore, many patients comb through the internet for medical information related to this specific topic. The purpose of this study was to assess the quality and integrity of the online available informative content about HR using acknowledged scoring instruments, proven quality markers and a novel designed specific HR score. Methods: In December 2016 the search term “hallux rigidus” was used to search Google (Google Inc., Mountain View, CA, USA) by three independent reviewers (two experienced orthopedic surgeons and one trained medical student). The content of the first 50 hits were analyzed by the use of specific scores including the DISCERN score, the Journal of the American Medical Association (JAMA) benchmark criteria and the Health On the Net code (HONcode) as a seal of quality for providing complete and transparent health-related information. Also the Flesch Reading Ease (FRE), the Flesch Kincaid Grade Level (FKGL), and the Gunning Fog Index (GFI) were recorded as indicators for readability. Websites were classified as follows: academic, commercial, government or non-profit organization (NPO), physician or group, and unspecified. A HR-specific content score was developed consisting of 19 specified items to evaluate the overall aspects about the procedure, management and potential complications. Results: Of the 50 screened websites, 37 (74%) were included for analysis. Of these 37 websites, 20 were from a physician or group, 8 were commercial, 6 were academic, 3 were governmental or NPO and 1 was unspecified. The mean DISCERN score of the websites was 46±10. The highest score was 65 points, whereas the lowest was 21. HON Code certification was present in six (16%) and HON seal in two websites (5%). The FRE, RKGL and GFI were 43,2±14, 8,1±2, and 6,7±2 respectively. The HR specific content score was 7±3. Conclusion: Quality and content of accessible information on the internet on HR was analyzed by three individuals by various objective scores. 37 websites were included in the analysis. The majority of websites provided poor information on the management of HR. Patients need to be aware of this fact. In the future measures need to be taken to improve quality and content of HR related websites.

Factors associated with initiation and persistence of urate-lowering therapy

BackgroundGout is the most common inflammatory arthritic disease and is caused by crystal deposition secondary to persistent hyperuricemia. Etiological treatment with urate-lowering therapy (ULT) has been available since the 1950s but previous studies have demonstrated suboptimal degree of treatment. In recent years we have seen recommendations for ULT earlier in the course of the disease, but there are few contemporary reports reflecting the current situation. Therefore we set out to investigate proportion receiving and persisting with ULT after gout diagnosis and predictors thereof.MethodA population-based cohort study using regional and national population-based registers. Cohort of patients (n = 7709) from western Sweden with incident gout aged 18 years and above from 2011 to 2013. An incident case of gout was defined as having been given a diagnosis of gout (ICD-10 M10, M14.0-14.1) not preceded by a gout diagnosis or a dispensation of ULT during the previous 5 years. Main outcome measures were cumulative incidence and predictors for start of, and persistence with, ULT in gout.ResultsWithin the first year after first gout diagnosis, 32% received ULT. Male sex, presence of diabetes or cardiovascular comorbidity, reduced kidney function but not diagnosed “end-stage kidney failure” increased the likelihood of receiving ULT. Of those starting ULT a majority (75%) did not persist with ULT treatment within the first 2 years. Age <50 years, lack of comorbidities, and “normal kidney function” or “end-stage kidney failure” were associated with non-persistence with ULT.ConclusionsOnly a minority of patients received ULT and a majority of these did not persist with treatment over the next 2 years. However, the older patients with renal impairment and comorbidities, possibly suffering from a more severe gout disease, were more likely to receive and persist with treatment. There is thus still room for considerable improvement with regards to management of ULT in gout.

Incidence and prevalence of gout in Western Sweden.

BackgroundThe aim of the present study was to describe prevalence and trends in the incidence of gout and patterns of urate-lowering treatment (ULT) in the Western Swedish Health Care Region (WSHCR) from 2002 to 2012.MethodsWe used regional and national healthcare registers to estimate the prevalence and incidence of gout in 2012, and trends in incidence for each calendar year from 2005 to 2012. We also investigated the pattern of ULT for gout using the Swedish Prescribed Drug Register.ResultsIn 2012, in the population aged 20 years and above, the prevalence of gout was 1.8 % (95 % confidence interval (CI) 1.77 to 1.82) and the incidence was 190 cases (95 % CI 180 to 200) per 100,000 person-years. Applying more strict definitions for a gout case rendered a prevalence of 1.36 % (95 % CI 1.34 to 1.38) and 0.5 (95 % CI 0.49 to 0.51) per 100,000 person-years, respectively. The incidence of gout increased steadily and significantly from 2005 to 2012, with an almost 50 % increase in the total population. There was no significant difference in the prevalence of gout in rural compared to urban areas. ULT was dispensed to only 42 % of patients with gout in 2012 who had ever been diagnosed with gout during the preceding 10-year period.ConclusionsGout is the most common arthritic disease in WSHCR, Sweden, and has increased substantially over the last decade, with only a minority of prevalent cases in 2012 receiving ULT.Electronic supplementary materialThe online version of this article (doi:10.1186/s13075-016-1062-6) contains supplementary material, which is available to authorized users.

The role of MCP-1-CCR2 ligand-receptor axis in chondrocyte degradation and disease progress in knee osteoarthritis.

Background Osteoarthritis (OA) is a common arthritic disease and multifactorial whole-joint disease. Interactions of chemokines and OA is inadequately documented.Results In vivo and in vitro studies were conducted to investigate monocyte chemoattractant protein 1 (MCP-1) and receptor chemokine (C–C motif) receptor 2 (CCR2) in chondrocyte degradation and cartilage degeneration. Chondrocytes from 16 OA patients and 6 normal controls were involved in this study. After stimulation of MCP-1, the expression of MCP-1 and CCR2 increased significantly (P < 0.001) and the expression of MMP-13 also increased (P < 0.05). MCP-1 stimulation also induced (or enhanced) the apoptosis of OA chondrocytes (P < 0.05). Additionally, the degradation of cartilage matrix markers (metalloproteinase 3 and 13, MMP3 and MMP13) in the culture medium of normal chondrocytes was also assessed. Furthermore, intra-articular injection of MCP-1 in mouse knees induced cartilage degradation and the CCR2 antagonist did not impede cartilage destroy in rats knees of monosodium iodoacetate (MIA) model.ConclusionsThe results of this study demonstrate that the MCP-1-CCR2 ligand-receptor axis plays a special role in the initiation and progression of OA pathology. Patients with ambiguous etiology can gain some insight from the MCP-1-CCR2 ligand-receptor axis.

Polymorphisms in GCKR, SLC17A1 and SLC22A12 were associated with phenotype gout in Han Chinese males: a case–control study

BackgroundGout is a common arthritic disease resulting from elevated serum uric acid (SUA) level. A large meta-analysis including 28,141 individuals identified nine single nucleotide polymorphisms (SNPs) associated with altered SUA level in a Caucasian population. However, raised SUA level alone is not sufficient for the development of gout arthritis and most of these SNPs have not been studied in a Han Chinese population. Here, we performed a case–control association analysis to investigate the relationship between these SUA correlated SNPs and gout arthritis in Han Chinese.MethodsA total of 622 ascertained gout p9atients and 917 healthy controls were genotyped. Genome-wide significant SNPs, rs12129861, rs780094, rs734553, rs742132, rs1183201, rs12356193, rs17300741 and rs505802 in the previous SUA study, were selected for our analysis.ResultsNo deviation from the Hardy–Weinberg equilibrium was observed either in the case or control cohorts (corrected p > 0.05). Three SNPs, rs780094 (located in GCKR, corrected p = 1.78E−4, OR = 0.723), rs1183201 (located in SLC17A1, corrected p = 1.39E−7, OR = 0.572) and rs505802 (located in SLC22A12, corrected p = 0.007, OR = 0.747), were significantly associated with gout on allelic level independent of potential cofounding traits. While the remaining SNPs were not replicated. We also found significant associations of uric acid concentrations with these three SNPs (rs780094 in GCKR, corrected p = 3.94E−5; rs1183201 in SLC17A1, corrected p = 0.005; rs505802 in SLC22A12, corrected p = 0.003) and of triglycerides with rs780094 (located in GCKR, corrected p = 2.96E−4). Unfortunately, SNP-SNP interactions for these three significant SNPs were not detected (rs780094 vs rs1183201, p = 0.402; rs780094 vs rs505802, p = 0.434; rs1183201 vs rs505802, p = 0.143).ConclusionsThree SUA correlated SNPs in Caucasian population, rs780094 in GCKR, rs1183201 in SLC17A1 and rs505802 in SLC22A12 were confirmed to be associated with gout arthritis and uric acid concentrations in Han Chinese males. Considering genetic differences among populations and complicated pathogenesis of gout arthritis, more validating tests in independent populations and relevant functional experiments are suggested in future.

Quadriceps muscle strength and its relationship to radiographic knee osteoarthritis

Quadriceps muscle strength and its relationship to radiographic knee osteoarthritis

PReS-FINAL-2135: Analysis of the HLA region in a large cohort of juvenile idiopathic arthritis cases identifies independent effects at HLA-DRB1

Juvenile idiopathic arthritis (JIA) is the most common arthritic disease of childhood and is caused by a combination of genes and environment. In the last few years great advances have been made in dissecting the genetic basis of JIA with now 17 confirmed susceptibility loci identified. One of these loci, the MHC region, has been established for many years but the complexity and the broad linkage disequilibrium (LD) across the region has rendered fine-mapping associations challenging. Novel imputation strategies can now be utilized to impute HLA classical alleles and amino acids across the region.

OP0212 Analysis of the immunochip in a large cohort of oligo- and polyarthritis juvenile idiopathic arthritis (JIA) cases confirms previous and identifies novel associations

BackgroundGenome wide association studies (GWAS) have been hugely successful in identifying susceptibility loci for autoimmune diseases. One interesting outcome of GWAS is the observation that many of the loci are...

Genetic susceptibility factors for psoriatic arthritis

Psoriatic arthritis (PsA) has a large genetic component to its heritability, yet investigation into the genetic basis of the disease has lagged behind other rheumatic diseases mainly because of the difficulty in defining classification criteria that would accurately differentiate it from other forms of inflammatory arthritis. However, using a variety of approaches, some confirmed associations have now been identified with PsA susceptibility, making a review of these recent developments timely. Family studies continue to suggest a large genetic contribution to PsA. Using a candidate gene approach, genes robustly confirmed to be associated with psoriasis vulgaris (PsV) have also been found to be associated with PsA (HLA-Cw*0602, IL23R, IL12B). There is less overlap reported with rheumatoid arthritis (RA) than PsV susceptibility loci but one report suggests that the AFF3 locus may be associated with both RA and PsA. Large, well powered genome-wide association studies are currently underway and should provide further insights into the cause of this common arthritic disease over the next few months. The bulk of evidence so far suggests that the genetic factors underlying PsV are also associated with PsA suggesting that future studies of PsV could include patients with PsA.

Community Oriented Program for the Control of Rheumatic Diseases: studies of rheumatic diseases in the developing world

The Community Orientated Program for the Control of Rheumatic Diseases (COPCORD) is based on collecting community data on rheumatic complaints and disability. After identifying significant problems, a search for disease risk factors is made, and control and treatment measures are recommended. This review covers the results of surveys in five countries-China, Brazil, Kuwait, Vietnam, and Australia-published in the last 18 months. Musculoskeletal pain is a major health problem in all surveys undertaken in both developed and developing countries. Knee and low back pain are the most frequent complaints, and osteoarthritis is the most common arthritic disease identified, particularly affecting the knees. The prevalence of rheumatoid arthritis is generally lesser in these studies compared with published surveys of white patients. However, the prevalence of gout varied widely, possibly because of changes in lifestyle and racial factors. Septic arthritis and rheumatic fever were rarely seen except in an Australian aboriginal community, pointing to improvement in standards of living and health care, at least in the urban settings, according to the Vietnamese authors. Population data are required on musculoskeletal complaints as a basis for decisions on health control and treatment programs. Surveys in five countries have identified the frequency of especially knee and low back pain, the prevalence of knee osteoarthritis, and the wide variability in the prevalence of gout, partly because of lifestyle and thus potentially correctable risk factors. Self-medication with potent pharmaceutical products in countries where doctors' prescriptions are not required is a recognizable health hazard.