Joint Destruction In Patients Research Articles

Ultrasonographic Synovitis Is Associated with the Development of Joint Destruction in Patients with Psoriatic Arthritis.

Psoriatic arthritis (PsA) is characterized by enthesitis. As persistent inflammation around joints results in bone and cartilage destruction and physical impairment, a detailed assessment of inflammation is essential. We previously reported the difference between clinical assessment (tenderness) and ultrasound (US) assessment (inflammation) of entheses. Herein, we investigated whether clinical or US assessment of joints and entheses can predict the progression of joint destruction in Japanese patients with PsA. Thirty joints and 14 entheses in 47 patients were assessed using US and clinical examination. The US greyscale (GS) and power Doppler (PD) scores at the ultrasonographic synovitis, the US active enthesitis count, and the clinical tender joint/entheses count were assessed. Additionally, the yearly radiographic progression of the Sharp-van der Heijde scoring method for PsA was assessed. Their correlations were investigated. About half of the patients with PsA experienced joint destruction during a follow-up period of 20.4 months. Progression of joint destruction in patients with PsA only correlated with joint GS and PD scores, reflecting the severity of ultrasonographic synovitis, not with the tender joint/entheses count. US examinations are essential for preventing joint destruction and physical impairment in patients with PsA.

Predictive value of baseline concomitant glucocorticoid for abatacept-mediated long-term inhibition of radiographic progression: insights from the KURAMA cohort

Abatacept (ABT) is a biological disease-modifying antirheumatic drug (bDMARDs) for rheumatoid arthritis (RA) when conventional synthetic DMARDs are ineffective. We aimed to evaluate the long-term effects of ABT on joint destruction in patients treated for over 2 years. Radiographic progression was evaluated using the van der Heijde-modified Total Sharp Score (mTSS) by two rheumatologists at ABT initiation and after 2 years. Multivariate logistic regression analysis was used to identify factors associated with structural remission, defined as the mean annual change in mTSS ≤0.5. Among the 111 patients included, 48 discontinued, and 63 continued ABT treatment until radiographic evaluation was performed. The rate of patients who achieved estimated TSS REM (yearly progression of van der Heijde modified total Sharp scores ≤0.5) was significantly lower in ABT-dropouts than in the ABT-continued group (69% vs. 48%, p = .0336 by Fisher’s exact test). Among the continued ABT cases, concomitant glucocorticoid treatment at ABT initiation was the strongest negative predictive factor of estimated TSS REM in univariate and multivariate logistic regression analyses. Radiographic progression after ABT administration should be evaluated separately for dropout and non-dropout cases. Glucocorticoids at the initiation of ABT may serve as a predictive factor for joint destruction in long-term ABT use.

Leukocyte Ig-like receptor A3 facilitates inflammation, migration and invasion of synovial tissue-derived fibroblasts via ERK/JNK activation.

Leukocyte Ig-like receptor A3 (LILRA3) is a soluble receptor belongs to the immunoglobulin superfamily. Our previous studies demonstrated that LILRA3 is a common genetic risk for multiple autoimmune diseases, including RA. Functional LILRA3 conferred increased risk of joint destruction in patients with early RA. We undertook this study to further investigate the pathological role of LILRA3 in joint inflammation of RA. Soluble LILRA3 was measured by ELISA. LILRA3 plasmids were transfected into human fibroblast-like synoviocytes (FLSs) using electroporation. Activation of extracellular signal-regulated kinase (ERK) and c-Jun N-terminal kinase (JNK) was determined by western blots. Cytokine transcripts were quantified by real-time PCR. Migratory and invasive capacities of FLSs were evaluated using transwell migration and Matrigel invasion assays. FLS apoptosis was analysed using flow cytometry. Colocalization of LILRA3, LILRB1 and HLA-G in RA-FLSs was visualized by immunofluorescence staining. Soluble LILRA3 was specifically expressed in synovial fluid and serum LILRA3 was significantly increased and positively correlated with disease activity/severity in RA patients. LILRA3 induced an increased expression of IL-6, IL-8 and MMP3 in RA-FLSs. In vitro LILRA3 stimulation or overexpression promoted RA-FLS migration and invasion, and enhanced phosphorylation of ERK/JNK. Inhibition of ERK/JNK resulted in suppression of IL-6/IL-8 expression in LILRA3-stimulated RA-FLSs. LILRA3 was co-localized with its homologue LILRB1 and shared ligand HLA-G in RA-FLSs. The present study provides the first evidence that soluble LILRA3 is a novel proinflammatory mediator involved in synovial inflammation by promoting RA-FLS activation, migration and invasion, probably through the ERK/JNK signalling pathways.

Safety and Efficacy of Golimumab in Rheumatoid Arthritis: A Prospective, Multicenter, Real-World Study from India

Abstract Background: Tumor necrosis factor (TNF) has been associated with inflammation and joint destruction in patients with rheumatoid arthritis (RA), and several anti-TNF agents, including golimumab, are currently in clinical use. This postmarketing surveillance (PMS) study was carried out at six rheumatology centers in India to assess the safety and efficacy of golimumab in patients with moderate-to-severe RA, in a real-world setting. Methods: This was a prospective, multicenter, open-label, single-arm, PMS study, where golimumab 50 mg subcutaneous was administered monthly as per locally approved prescribing regulations. The primary endpoint was to assess the safety of golimumab. Health Assessment Questionnaire-Disability Index (HAQ-DI), Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F), auto-injector satisfaction/user-friendliness, injection-site pain/reactions, and 28-joint Disease activity score (DAS-28) including erythrocyte sedimentation rate (ESR) (DAS-28-ESR) and C-reactive protein (CRP) (DAS-28 CRP), were evaluated as per investigator’s routine practice. Results: Over 6 months, 120 patients were enrolled and 109 completed the study. Sixty-two (51.7%) patients experienced ≥1 treatment-emergent adverse events (TEAEs). The majority of TEAEs reported in the study were mild to moderate in severity. No deaths were reported. The mean (standard deviation [SD]) change from baseline in HAQ-DI (−0.9 [0.65]) and FACIT-F (14.8 [10.20]) suggested improvement in physical function and fatigue, respectively. The majority of patients (n = 77 [64.2%]) were “very satisfied” on the satisfaction/user-friendliness parameters of auto-injector and majority (n = 99 [91.7%]) did not experience injection-site reactions. Mean (SD) change from baseline of DAS-28 scores (not assessed for all patients; DAS-28 ESR [n = 62]: −2.0 [1.25]) indicated an improvement in disease activity. Conclusions: Golimumab (50 mg) in combination with methotrexate was found to be safe and well-tolerated in Indian patients with moderate-to-severe RA. No new safety signals emerged.

Endothelial Stat3 activation promotes osteoarthritis development.

The mechanism of the balance between subchondral angiogenesis and articular damage within osteoarthritis (OA) progression remains a mystery. However, the lack of specific drugs leads to limited clinical treatment options for OA, frequently failing to prevent eventual joint destruction in patients. Increasing evidence suggests that subchondral bone angiogenesis precedes cartilage injury, while proliferating endothelial cells (ECs) induce abnormal bone formation. Signal transducer and activator of transcription 3 (Stat3) is triggered by multiple cytokines in the OA microenvironment. Here, we observed elevated Stat3 activation in subchondral bone H-type vessels. Endothelial Stat3 activation will lead to stronger cell proliferation, migration and angiogenesis by simulating ECs in OA. In contrast, either Stat3 activation inhibition or knockdown of Stat3 expression could relieve such alterations. More interestingly, blocking Stat3 in ECs alleviated angiogenesis-mediated osteogenic differentiation and chondrocyte lesions. Stat3 inhibitor reversed surgically induced subchondral bone H-type vessel hyperplasia in vivo, significantly downregulating vessel volume and vessel number. Due to the reduced angiogenesis, subchondral bone deterioration and cartilage loss were alleviated. Overall, our data suggest that endothelial Stat3 activation is an essential trigger for OA development. Therefore, targeted Stat3 blockade is a novel promising therapeutic regimen for OA.

Association of the Clinical and Radiographic Findings at Onset With Future Joint Destruction in Patients With Rheumatoid Arthritis.

Since inflammation can cause joint destruction in patients with rheumatoid arthritis (RA), it is assumed that joints that are symptomatic at onset are at higher risk of joint destruction; however, this theory remains controversial. This study aimed to investigate whether the progression of joint destruction in hands and feet could be predicted from the clinical and radiographic findings at onset. This study included 75 patients who visited our hospital within one year after the onset of RA with at least 12 months of follow-up. We examined the positive predictive value (PPV) and the sensitivity of the clinical findings (swelling, tenderness, and squeeze test) and joint destruction at onset for the progression of joint destruction. Sixty joints (45 metacarpophalangeal and proximal interphalangeal joints, 15 metatarsophalangeal joints) exhibited progressive structural destruction during the study course. Both the PPV and the sensitivity of the clinical findings for the progression of joint destruction were low; however, only the sensitivity of the squeeze test for the feet was high. The PPV of joint destruction at onset was higher than the clinical findings, and the sensitivity of joint destruction at onset was as high as the squeeze test for the feet. Conclusions: Regular follow-up with imaging is necessary regardless of symptoms and joint destruction at the onset. Adding the squeeze test for feet to routine clinical practice may help predict the risk of joint destruction for the feet.

Baseline erythrocyte sedimentation rate level predicts long-term inhibition of radiographic progression by tocilizumab: the KURAMA cohort

The short-term effect of tocilizumab (TCZ) on the radiographic progression of rheumatoid arthritis has been reported; however, reports on its long-term effects are scarce. In this study, we aimed to evaluate its long-term effects on joint destruction in patients who had been treated with TCZ for at least two years and for whom X-rays were available. Radiographic progression was evaluated with modified Total Sharp Score (mTSS), and structural remission was defined as the mean annual change in mTSS ≤0.5. Of the 59 patients included in this study (median age, 62 years; female, 81.4%), 34 patients (57.6%) achieved structural remission. Patients who achieved structural remission were relatively younger (59 years vs. 64 years, p = .06), had relatively higher proportion of anti-citrullinated protein antibody positivity (91.2% vs. 72.0%, p = .08), relatively lower C-reactive protein level (0.6 mg/dL vs. 2.2 mg/dL, p = .05), and significantly lower erythrocyte sedimentation rate (ESR) level (28.0 mm/h vs 65.5 mm/h, p = .003) than those who did not. Multivariate logistic regression analysis demonstrated that the baseline ESR level was significantly associated with structural remission (odds ratio, 0.98; 95% confidence interval: 0.96–0.99, p = .049). The baseline ESR level is a critical determinant of the long-term effect of TCZ on joint destruction.

Serum 14-3-3 ETA levels in ankylosing spondylitis with pure axial involvement: Could it be a potential biomarker to assess disease activity?

Aim: The 14-3-3η (eta) protein has been associated with the severity of the disease and joint destruction in patients with rheumatoid arthritis (RA). It has also been shown to be likely to be effective in inflammatory events. We aimed to investigate whether eta levels could be a potential biomarker in the diagnosis of ankylosing spondylitis (AS) and in the determination of disease activity in patients with AS.Methods: This study included 51 patients diagnosed with AS and 49 healthy controls aged 20-65 years. The routine hemogram, erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP) levels were measured and the neutrophil/lymphocyte ratio (NLR) was calculated in the patients. The serum eta levels were also measured in the patient and healthy control groups. The Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and the Ankylosing Spondylitis Disease Activity Score (ASDAS) were used to assess disease activity. Sacroiliac joint radiographs of the patients were evaluated and the sacroiliitis was graded.Results: There was no statistically significant correlation between the degree of sacroiliitis, disease activity indices, and eta levels. There was no statistically significant correlation between eta levels and hematological parameters except for CRP. There was a negative, weak, and statistically significant relationship between the patients’ eta levels and CRP (r=-0.277; p=0.049). We could not find any correlation between the degree of sacroiliitis, disease activity indexes, and serum eta levels in AS patients.Conclusion: Serum eta levels are not a good biomarker for detecting disease activity in patients with ankylosing spondylitis. The 14-3-3η protein may play a more active role in rheumatic diseases where peripheral joint involvement is prominent.

Psoriatic arthritis successfully treated with second-line anti-interleukin-6 treatment: a case report and review of the literature

BackgroundPsoriatic arthritis treatment with antitumor necrosis factor has been shown to reduce disease activity. Nonetheless, more than 30% of patients do not achieve a sufficient response to tumor necrosis factor blockers. Currently, treatment with interleukin-6 inhibitors is expected to be effective and suppress the joint destruction in patients with psoriatic arthritis; however, evidence regarding their efficacy is limited to a few reports.Case presentationA 78-year-old Japanese woman with psoriatic arthritis associated with rapid joint destruction was successfully treated with a second-line anti-interleukin-6 receptor agent. In this case, a tumor necrosis factor inhibitor induced an inadequate response, and the right knee and left hip joints required artificial joint replacement surgery. However, second line treatment with anti-interleukin-6 treatment was effective, and the right elbow joint function was preserved.ConclusionsWe experienced a case of psoriatic arthritis, in which anti-interleukin-6 treatment repaired a bone cyst in the lateral epicondyle of the humerus and enthesitis of the distal interphalangeal joints. The patient is currently in clinical remission with no restrictions in daily life activities. Anti-interleukin-6 treatment may address the unmet needs of patients with psoriatic arthritis who are resistant or intolerant to antitumor necrosis factor treatment, with rapidly destructive large joints but with well-managed skin manifestations.

Effect of continuous administration of tocilizumab for 5 years or more on the progression of wrist joint destruction in patients with rheumatoid arthritis

Effect of continuous administration of tocilizumab for 5 years or more on the progression of wrist joint destruction in patients with rheumatoid arthritis

Neuropathic arthropathy of the shoulder caused by syringomyelia: a case report

Neuropathic or Charcot arthropathy is a chronic degenerative disease that causes joint destruction in patients with abnormal sensation and proprioception. Charcot shoulder is rare and its most common cause is syringomyelia. Patients present insidiously with joint instability, swelling and dysfunction. Pain may not be present due to sensory loss. The key to successful management is early diagnosis by a thorough history, physical examination and imaging after exclusion of inflammatory, infectious and malignant etiology. Most commonly, Charcot shoulders are managed conservatively, although surgical intervention has recently proven to be a promising treatment for recovering function in selected patients. We present a 52-year-old female with chronic complaints of sensory loss and swelling of her right upper limb that progressively evolved for shoulder pain and marked dysfunction, which led to the diagnosis of syringomyelia associated with Chiari I malformation and for what she had undergone posterior fossa craniectomy. Considering her past medical history and after exclusion of other etiology, she was diagnosed with shoulder neuropathic arthropathy. She initiated conservative treatment but symptomatic and functional improvement was poor, highlighting the importance of early diagnosis and management of these patients.

Efficacy of Intra-Articular Triamcinolone Acetonide Injections for Wrist Pain in Rheumatoid Arthritis Patients: A Retrospective Study

Background: Synovectomy, arthroplasty, and other surgical procedures are generally used to correct wrist joint destruction in patients with rheumatoid arthritis (RA). Methodology: We unilaterally injected 20 mg of triamcinolone acetonide and 5 mL of 1% lidocaine hydrochloride of RA patients with joints pain who refused surgery. We then evaluated the clinical benefit and safety of intra-articular triamcinolone acetonide by analyzing data on (1) the number of injections with Larsen’s grade and whether a biologic was used or not, (2) decrease in visual analog scale pain, (3) changes in carpal height ratio, radio carpal distance ratio and radial rotation angle in dorso-palmar plain X-ray imaging, and (4) the side effects of triamcinolone acetonide injection into the joints. Results: The mean number of injections per patient was less than 5 times, and sufficiently reduced or eliminated joints pain. X-ray evaluation did not reveal progress of joint destruction due to triamcinolone acetonide. No side effects of injection did not occur. Conclusions: It was found that joint injection of triamcinolone acetonide can reduce joint pain and suppress joint destruction, and it is possible that surgery will not be necessary in the future.

A genome-wide association study identifying the SNPs predictive of rapid joint destruction in patients with rheumatoid arthritis.

Rheumatoid arthritis (RA) is a common chronic autoimmune disease leading to joint destruction. The aim of the present study was to identify the genomic factors predictive of susceptibility to joint destruction in patients with RA by performing a genome-wide association study of genetic variants, including single nucleotide polymorphisms (SNPs). The study sample included 228 patients with a diagnosis of RA in the past 5 years. Patients were classified into rapid (total Sharp score/years of RA, ≥50) and slow (total Sharp score/years of RA, <50) joint destruction groups for analysis. The association between the genome-wide SNP analysis and joint destruction was evaluated. The following SNPs were strongly associated with rapid radiographic joint destruction: rs2295926 (P<1x10-7), belonging to the N-acetylgalactosaminyltransferase 12 (GALNT12) gene and rs11958855 (P<1x10-6), belonging to the KCNN2 gene (associated with the potassium calcium-activated channel subfamily). The identification of genetic predictors of rapid joint destruction in RA (GALNT12 and KCNN2) may provide information regarding potential therapeutic targets, and this information may be used to assist in the management RA disease progression, thereby improving the functional outcomes for patients.

Depression and severity of articular destruction in patients with rheumatoid arthritis

To assess the influence of anxiety and depressive disorders on joint destruction in patients with rheumatoid arthritis (RA). 128 RA-patients were included, 87% were women with a mean age of 47.411.3 years and a median of RA duration 96 [48; 228] months. At the inclusion most patients had moderate (n=56, 43.7%) and severe (n=48, 37.5%) disease activity according to DAS28. Joint destruction was classified as maximal in patients with radiographic stage III, IV and/or osteonecrosis) and minimal in patients with stage I, II and no osteonecrosis. Pain intensity was measured with the BPI (Brief Pain Inventory) scale, severity of fatigue with fatigue severity scale (FSS), clinically important fatigue was diagnosed in patients with FSS4. Anxiety and depressive disorders (ADD) were diagnosed by a licensed psychiatrist in 123 (96.1%) of RA-patients in accordance with ICD-10 in semi-structured interview. Severity of depression and anxiety was evaluated with Montgomery-Asberg Depression Rating Scale (MADRS) and Hamilton Anxiety Rating Scale (HAM-A). RA-patients with ADD were divided into the following treatment groups: 1 сDMARDs (n=39), 2 сDMARDs+PPT (sertraline or mianserine), n=43, 3 сDMARDs+bDMARDs (n=32), 4 сDMARDs+bDMARDs+PPT (sertraline or mianserine), n=9. Biologics treatment duration varied from 1 to 6 years, antidepressants from 6 to 96 weeks. 83 (67.5%) RA patients were assessed at five-years follow-up. Linear regression analysis was conducted to determine factors associated with maximal join destruction. According to linear regression analysis, maximal joint destruction at 5 years follow-up was associated with higher baseline BPImax, longer RA and ADD duration, clinically important fatigue at baseline, baseline extraarticular RA manifestations, recurrent depressive disorder at 5-years follow-up and treatment with cDMARDs only. Recurrent depressive disorder without antidepressant treatment is an important predictor of progression of joint destruction in patients with rheumatoid arthritis.

Reduced Skeletal Muscle Independently Predicts One-Year Aggravated Joint Destruction In Patients With Rheumatoid Arthritis

Background: Numerous cross-sectional studies have reported the associations between rheumatoid arthritis (RA) and reduced skeletal muscle. We firstly explored the dynamic change of skeletal muscle and its effect on RA clinical outcomes in a real-world prospective cohort. Methods: Consecutive RA patients were treated according to the treat-to-target strategy and completed at least one-year follow-up. Clinical data and muscle index (assessed by bioelectric impedance analysis) were collected at baseline and visits at 3, 6, 9 and 12 months. Myopenia was defined by appendicular skeletal muscle mass index ≤7.0kg/m2 in men and ≤5.7kg/m2 in women. One-year radiographic progression as primary outcome was defined by a change in the total Sharp/van der Heijde modified score ≥0.5 units. Results: Among 348 recruited patients, 315 RA patients (mean age 47.9 years, 84.4% female) completed one-year follow-up. There were 143 (45.4%) RA patients showing myopenia at baseline. Compared with those without baseline myopenia, RA patients with baseline myopenia had higher rate of one-year radiographic progression (43.4% vs. 21.5%, all P<0.05). Baseline myopenia was an independent risk factor for one-year radiographic progression (AOR=2.360, 95%CI: 1.076-5.179), especially among RA patients in remission at baseline (AOR=3.492, 95%CI: 1.257-9.699). Further analysis of six subtypes of dynamic skeletal muscle change showed that newly acquired myopenia at endpoint was associated with radiographic progression (AOR=5.377, 95%CI: 1.599-18.080). Conclusions: Reduced skeletal muscle is an independent predicting factor for one-year aggravated joint destruction in both active and remission RA. The importance of dynamic monitoring of skeletal muscle and muscle improvement therapy are worth exploration. Funding Statement: This work was supported by National Natural Science Foundation of China (grant no. 81971527 and 81801606), Guangdong Natural Science Foundation (grant no. 2019A1515011928 and 2018A030313541), and Science and Technology Program of Guangzhou (grant No. 201904010088). Declaration of Interests: Jian-Zi Lin, Yin Liu, Jian-Da Ma, Ying-Qian Mo, Chu-Tao Chen, Le-Feng Chen, Qian-Hua Li, Ze-Hong Yang, Dong-Hui Zheng, Li Ling, Pierre Miossec, Lie Dai declare that they have no competing interests. Ethics Approval Statement: This study was conducted in compliance with the Helsinki Declaration and the protocol was approved by the Medical Ethics Committee of Sun Yat-sen Memorial Hospital (SYSEC-2009-06 and SYSEC-KY-KS-012). All participants gave their written informed consent before clinical data collection.

Reduced skeletal muscle independently predicts 1-year aggravated joint destruction in patients with rheumatoid arthritis.

Background:Numerous cross-sectional studies have reported the associations between rheumatoid arthritis (RA) and reduced skeletal muscle. We firstly explored the dynamic change of skeletal muscle and its effect on RA clinical outcomes in a real-world prospective cohort.Methods:Consecutive RA patients were treated according to the treat-to-target strategy and completed at least 1-year follow up. Clinical data and muscle index (assessed by bioelectric impedance analysis) were collected at baseline and visits at 3, 6, 9 and 12 months. Myopenia was defined by appendicular skeletal muscle mass index ⩽7.0 kg/m2 in men and ⩽5.7 kg/m2 in women. A 1-year radiographic progression as primary outcome was defined by a change in the total Sharp/van der Heijde modified score ⩾0.5 units.Results:Among 348 recruited patients, 315 RA patients (mean age 47.9 years, 84.4% female) completed 1-year follow up. There were 143 (45.4%) RA patients showing myopenia at baseline. Compared with those without baseline myopenia, RA patients with baseline myopenia had higher rate of 1-year radiographic progression (43.4% versus 21.5%, all p < 0.05). Baseline myopenia was an independent risk factor for 1-year radiographic progression with adjusted odds ratio (AOR) of 2.5-fold, especially among RA patients in remission at baseline both defined by Disease Activity Score in 28 joints (DAS28) including C-reactive protein (DAS28-CRP) or erythrocyte sedimentation rate (DAS28-ESR) with AOR of 18.5~42.9-fold. Further analysis of six subtypes of dynamic skeletal muscle change showed that newly acquired myopenia at endpoint was associated with radiographic progression (AOR of 5.4-fold).Conclusions:Reduced skeletal muscle is an independent predicting factor for 1-year aggravated joint destruction, especially in remission RA. The importance of dynamic monitoring of skeletal muscle and muscle improvement therapy are worth exploration.

Serum and synovial matrix metalloproteinases 1 and 3 in patients with early rheumatoid arthritis: potentially prospective biomarkers of ultrasonographic joint damage and disease activity

BackgroundMatrix metalloproteinase-1 (MMP-1) and MMP-3 play important roles in the pathogenesis of rheumatoid arthritis (RA) and have been suggested as markers of disease activity and joint damage.Objective The aim was to analyze the clinical significance of MMP-1 and MMP-3 in relation to markers of disease activity and degree of joint destruction in patients with early RA at presentation and after 6 months.Patients and methodsBaseline levels of serum MMP-1 and MMP-3 were assessed in 50 patients with early RA (symptoms <1 year), 20 patients with osteoarthritis (OA), and 20 age-matched and sex-matched healthy controls. Serum MPP-1 and MPP-3 were correlated with disease activity markers [erythrocyte sedimentation rate (ESR), C-reactive protein, disease activity score 28–ESR] and radiographic joint damage using simple erosion narrowing score and musculoskeletal ultrasound of wrist and hand joints. Baseline synovial fluid MMP-1 and MMP-3 levels were evaluated for 20 patients indicated for arthrocentesis.ResultsBaseline serum MMP-1 and MMP-3 were significantly higher in RA group versus OA group and healthy controls (P<0.001). Synovial MMP-1 and MMP-3 levels were significantly higher in RA versus OA group. Serum MMP-1 and MMP-3 levels significantly correlated with rheumatoid factor titers, anticyclic citrullinated peptide, disease activity score 28-ESR score, joint erosions, and Outcome Measures in Rheumatology score of synovitis and Doppler signals. Serum MMP-1 did not correlate with C-reactive protein, but significantly correlated with the number of erosions at presentation and on follow-up. The number of patients with erosions and the number of erosions per patient increased after 6 months and correlated with serum MMP-1 and MMP-3. The best cutoff values of serum MMP-1 and MMP-3 to discriminate between RA and healthy controls were greater than 20 and greater than 50ng/ml, respectively.ConclusionElevated serum levels of MMP-1 and MMP-3 can be used as an indicator of disease activity in patients with early RA and can reflect the degree of joint damage and correlate with the number of new joint erosions.

Inhibition of cyclooxygenase-2 activity in subchondral bone modifies a subtype of osteoarthritis

Osteoarthritis (OA) causes the destruction of joints. Its pathogenesis is still under investigation, and there is no effective disease-modifying therapy. Here, we report that elevated cyclooxygenase-2 (COX-2) expression in the osteocytes of subchondral bone causes both spontaneous OA and rheumatoid arthritis (RA). The knockout of COX-2 in osteocytes or treatment with a COX-2 inhibitor effectively rescues the structure of subchondral bone and attenuates cartilage degeneration in spontaneous OA (STR/Ort) mice and tumor necrosis factor-α transgenic RA mice. Thus, elevated COX-2 expression in subchondral bone induces both OA-associated and RA-associated joint cartilage degeneration. The inhibition of COX-2 expression can potentially modify joint destruction in patients with arthritis.

LncRNA‑NR024118 overexpression reverses LPS‑induced inflammatory injury and apoptosis via NF‑κB/Nrf2 signaling in ATDC5 chondrocytes.

Osteoarthritis (OA) is one of the most prevalent types of chronic joint diseases. Chondrocytes survival is closely associated with the destruction of joints in patients with OA. Long noncoding RNAs (lncRNAs) serve a critical role in OA. However, to the best of our knowledge, the role of lncRNAs NR024118 in OA has not been examined. In the present study, the expression levels of NR024118 in lipopolysaccharide (LPS)-induced chondrocytes was measured using reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and the apoptosis levels of cells was determined using flow cytometry. The levels of scavenged reactive oxygen species and expression levels of the antioxidant enzymes including superoxide dismutase (SOD), catalase (CAT), and heme oxygenase-1 (HO-1) were measured using specialized detection kits. The expression of interleukin (IL)-1β, IL-6 and IL-18 were measured using ELISA. Expression of the cell apoptosis markers Bcl-2, Bax, Bcl-2-like protein 11, NF-κB, phosphorylated (p)-NF-κB inhibitor β (IκBβ), IκBβ, p-transcription factor p65 (p65) and p65, and nuclear factor erythroid-2 related factor 2 (Nrf2) signaling pathways-associated proteins, Nrf2, HO-1 and quinone oxidoreductase-1 were detected by western blot analysis and RT-qPCR. The results indicated that in ATDC5 cells, apoptosis, oxidative stress and inflammation were significantly increased and the expression level of NR024118 was significantly decreased by LPS-mediated induction. NR024118 overexpression significantly reversed the effects of LPS treatment in the ATDC5 cell line. In addition, the overexpression of NR024118 decreased NF-κB expression levels and activated the Nrf2 signaling pathways in LPS-induced ATDC5 cells. The present study demonstrated that NR024118 attenuated the effects of LPS-induction on ATDC5 cells. These results suggest that NR024118 may be a potential target for diagnosis and treatment of OA.

CD21-/low B cells associate with joint damage in rheumatoid arthritis patients.

Depletion of B cells is beneficial in rheumatoid arthritis (RA) patients with autoantibodies to citrullinated proteins (ACPA) and/or the Fc portion of immunoglobulins (rheumatoid factor [RF]), suggesting a role for B cells in disease pathogenesis. To date, however, the identity of specifically pathogenic B cell subsets has not been discovered. One candidate population is identified by the low expression or absence of complement receptor 2 (CD21-/low B cells). In this study, we sought to determine whether there was any correlation between CD21-/low B cells and clinical outcome in patients with established RA, either ACPA+ /RF+ (n=27) or ACPA- /RF- (n=10). Healthy donors (n=17) were included as controls. The proportion of the CD21-/low CD27- IgD- memory B cell subset in peripheral blood (PB) was significantly increased in ACPA+ /RF+ RA patients compared with healthy donors, and the frequency of this subset correlated with joint destruction (r=0.57, P<0.04). The levels of the chemokines CXCL-9 and CXCL-10 were higher in synovial fluid than in plasma, and PB CD21-/low cells expressed the receptor, CXCR3. In synovial fluid, most of the B cells were CD21-/low , approximately 40% of that population was CD27- IgD- , and a third of those expressed the pro-osteoclastogenic factor receptor activator of the nuclear factor κB ligand (RANKL). This subset also secreted RANKL, in addition to other factors such as IL-6, even in the absence of stimulation. We interpret these data as reason to propose the hypothesis that the CD27- IgD- subset of CD21-/low B cells may mediate joint destruction in patients with ACPA+ /RF+ RA.