Severe Synovitis Research Articles

Validation of the ankle-specific pediatric arthritis ultrasound scoring system in children with juvenile idiopathic arthritis

ObjectiveTo validate the ankle-specific Pediatric Arthritis Ultrasound Scoring System (PAUSS-ankle) in children with juvenile idiopathic arthritis (JIA). MethodsPatients with a diagnosis of JIA prospectively underwent a standard clinical assessment and musculoskeletal ultrasound (MSUS) of one or both ankles. B-mode and Power-Doppler mode MSUS images were acquired and scored according to the PAUSS-ankle protocol. A subset of patients received a contrast-enhanced MRI (ceMRI) of the affected ankle. ceMRI scoring for synovitis was performed according to the Rheumatoid Arthritis MRI System (RAMRIS). Test characteristics of the PAUSS-ankle scores were evaluated with ceMRI as reference. Associations between the findings on physical examination, PAUSS-ankle, and RAMRIS were investigated. ResultsThirty-two patients with JIA contributed 63 MSUS and 15 ceMRIs of the ankles. The PAUSS-ankle total B-mode score had a moderate correlation with physical examination findings (correlation (r)=0.43, p < 0.001). The PAUSS-ankle B-mode score ≥1 exhibited a sensitivity of 79 % and specificity of 100 %, demonstrating excellent diagnostic accuracy with an area under the curve (AUC)= 0.89 (confidence intervals, CI, 0.78–1.00) while clinical assessment had a sensitivity of 57 % and AUC= 0.71 (CI: 0.58–0.85). The PAUSS-ankle B-mode score had significant strong correlations (r = 0.68–0.90, p < 0.005) with the RAMRIS for the assessment of disease severity for each joint area and the ankle joint as a whole. ConclusionOur findings demonstrate excellent diagnostic accuracy of the PAUSS-ankle in detecting the presence and severity of ankle synovitis when compared to ceMRI. The PAUSS-ankle holds significant promise as an accurate measurement that may complement current clinical standards.

Arthroscopic Assessment of Temporomandibular Joint Pathologies-Is It Possible for Non-Specialists in Arthroscopy? Analysis of Variability and Reliability of Dental Students' Ratings after a Comprehensive One-Semester Introduction.

Background: Arthroscopy of the temporomandibular joint (TMJ) plays a long-established role in the diagnostics and therapy of patients suffering from arthrogenic temporomandibular disorders (TMDs), which do not respond adequately to conservative/non-invasive therapy. However, the interpretation of arthroscopic findings remains challenging. This study investigates the reliability and variability of assessing arthroscopic views of pathologies in patients with TMDs by non-specialists in arthroscopy and whether a standardized assessment tool may improve correctness. Methods: Following a comprehensive one-semester lecture, dental students in the clinical stage of education were asked to rate 25 arthroscopic views (freeze images and corresponding video clips) regarding the severity of synovitis, adhesions, and degenerative changes on a scale of 0-10 (T1). The results were compared to ratings stated by two European-board-qualified academic OMF surgeons. In a second round (T2), the students were asked to repeat the ratings using a 10-point rating scheme. Results: With regard to all three subcategories, congruency with the surgeons' results at T1 was at a low level (p < 0.05 in 19/75 cases) and even decreased at T2 after the implementation of the TMDs-SevS (p < 0.05 in 38/75 cases). For both T1 and T2, therefore, the inter-rater agreement was at a low level, showing only a slight agreement for all three subcategories (Fleiss' Kappa (κ) between 0.014 and 0.099). Conclusions: The judgement of the arthroscopic pathologies of the TMJ remains an area of temporomandibular surgery that requires wide experience and training in TMDs to achieve expertise in TMJ arthroscopic assessments, which cannot be transferred by theoretical instruction alone.

Therapeutic Effects of Mesenchymal Stem Cells Derived from Bone Marrow and Adipose Tissue in a Rat Model of Temporomandibular Osteoarthritis

ObjectivesTo examine the potential of intra-articular administration of mesenchymal stem cells (MSCs) derived from bone marrow or adipose tissue to mitigate synovial inflammation in a rat model of temporomandibular joint (TMJ) osteoarthritis (OA). MethodsIn this experimental study, 40 rats were divided into 4 groups: (1) Control group; (2) Untreated TMJ-OA group; (3) TMJ-OA group treated with bone marrow-derived MSCs; (4) TMJ-OA group treated with adipose tissue-derived MSCs. The TMJ-OA model was established by inducing synovial inflammation through the intra-articular administration of complete Freund’s adjuvant (CFA). After 8 weeks of TMJ-OA establishment, the animals were sacrificed and each mandibular condyle was extracted for histological evaluation. ResultsThe untreated TMJ-OA group had significantly higher synovial inflammation, as indicated microscopically by higher grades of synovial membrane hyperplasia and adhesion, vascular vasodilation, and fibrin deposition than the control group (p < 0.001). Both TMJ-OA groups treated with MSCs had lower grades of synovial inflammation and less severe synovitis than the untreated TMJ-OA group (p < 0.001). The TMJ-OA group treated with adipose tissue-derived MSCs showed lower grades of synovial membrane hyperplasia and higher grades of fibrin deposition than the that treated with bone marrow-derived MSCs (p < 0.001). Other indicators of synovial inflammation and synovitis severity were comparable between the two treatment groups. ConclusionsAdministration of CFA to the TMJ-OA rat model augmented synovial inflammation. Intra-articular administration of MSCs derived from either bone marrow or adipose tissue attenuated the microscopic manifestations of this inflammation, indicating the therapeutic potential of this treatment for TMJ-OA.

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.

Effectiveness of Genicular Artery Embolization for Reducing Synovitis as Assessed by Contrast-Enhanced MR Imaging in Knee Osteoarthritis: A Pilot Study

PurposeTo investigate the impact of genicular artery embolization (GAE) on synovitis in knee osteoarthritis (OA) using contrast-enhanced magnetic resonance (MR) imaging and to assess its predictive role in pain response. Materials and MethodsA single-center retrospective analysis was conducted using contrast-enhanced MR imaging on 33 patients treated with GAE for knee OA between December 2022 and March 2023. MR assessments before the procedure and at 3 months after embolization were utilized in a semiquantitative scoring system for synovitis severity and distribution analysis. Pain and function through Western Ontario and McMaster Universities Osteoarthritis Index and visual analog scale scores were also assessed. ResultsSignificant synovitis reduction was noted after GAE, particularly in parapatellar and periligamentous areas. Synovial contrast enhancement scores significantly decreased from 5.1 (SD ± 2.0) to 2.9 (SD ± 2.0) at 3 months (P < .001), with a moderate negative correlation between synovial enhancement scores and pain levels (P = .005). ConclusionsGAE significantly reduced synovitis in knee OA, evidenced by contrast-enhanced MR imaging. The correlation between preprocedural synovial contrast enhancement scores and pain relief after the procedure, although promising, requires careful interpretation because of the complex factors affecting pain in knee OA.

“Fish head” sign on magnetic resonance imaging in knee synovitis – An observational pilot study

Objectives: Synovitis, characterized by joint inflammation, has various causes, including inflammatory, infectious, degenerative, traumatic, hemorrhagic, and neoplastic origins. Early detection is essential, and magnetic resonance imaging (MRI) plays a vital role in identifying synovial diseases before they lead to irreversible joint damage. It provides characterization and non-invasive monitoring of synovial changes. This study introduces and describes the novel “fish head” sign, a unique identifier of early knee synovitis on MRI. Materials and Methods: We conducted a retrospective analysis of 50 MRI cases of patients with rheumatoid arthritis (RA)-related synovitis who were referred to our clinic due to knee pain. The primary aim was to uncover insights into the “fish head” sign, a unique imaging feature observed on sagittal views of the lateral meniscus using proton density (PD)-weighted fat-suppressed sequences. Results: Within our cohort of 50 patients, 20 displayed the fish head sign on MRI, whereas 30 did not exhibit this sign. 17/20 of these patients had mild synovitis, 1/20 patients had moderate synovitis, and 2/20 patients had severe synovitis. Fourteen patients with synovitis did not demonstrate the sign. Conclusion: Our study introduces the “fish head” sign observed in PD MRI images of early knee synovitis among patients with RA. This unique sign has the potential to serve as a diagnostic tool or adjunct for patients with synovitis of the knee, reducing the need for contrast-enhanced imaging. This discovery offers valuable insights into the field of synovitis assessment, imaging, and diagnosis.

Interleukin-35 protein inhibits osteoclastogenesis and attenuates collagen-induced arthritis in mice.

Rheumatoid arthritis (RA) is a chronic autoimmune disease. Its pathological features include synovial inflammation, bone erosion, and joint structural damage. Our previous studies have shown that interleukin (IL)-35 is involved in the pathogenesis of bone loss in RA patients. In this study, we are further evaluating the efficacy of IL-35 on collagen-induced arthritis (CIA) in the mouse model.Male DBA/1J mice (n = 10) were initially immunized, 2 μg/mouse IL-35 was injected intraperitoneally every week for 3 weeks after the establishment of the CIA model. Clinical arthritis, histopathological analysis, and three-dimensional micro-computed tomography (3D micro-CT) were determined after the mice were anesthetized on the 42th day. In vitro, RANKL/M-CSF induced mouse preosteoclasts (RAW264.7 cells line) was subjected to antiarthritis mechanism study in the presence of IL-35.The results of clinical arthritis, histopathological analysis, and 3D micro-CT, the expression of RANK/RANKL/OPG axis, inflammatory cytokines, and osteoclastogenesis-related makers demonstrated decreasing severity of synovitis and bone destruction in the ankle joints after IL-35 treatment. Furthermore, IL-35 attenuated inflammatory cytokine production and the expression of osteoclastogenesis-related makers in a mouse preosteoclasts cell line RAW264.7. The osteoclastogenesis-related makers were significantly reduced in IL-35 treated RAW264.7 cells line after blockage with the JAK/STAT1 signaling pathway. These results demonstrated that IL-35 protein could inhibits osteoclastogenesis and attenuates CIA in mice.We concluded that IL-35 can exhibit anti-osteoclastogenesis effects by reducing the expression of inflammatory cytokines and osteoclastogenesis-related makers, thus alleviating bone destruction in the ankle joint and could be a potential therapeutic target for RA.

S100A12 is involved in the pathology of osteoarthritis by promoting M1 macrophage polarization via the NF-κB pathway

ABSTRACT Background Osteoarthritis (OA) is a degenerative joint disease that affects millions worldwide. Synovitis and macrophage polarization are important factors in the development of OA. However, the specific components of synovial fluid (SF) responsible for promoting macrophage polarization remain unclear. Methods Semi-quantitative antibody arrays were used to outline the proteome of SF. Differential expression analysis and GO/KEGG were performed on the obtained data. Immunohistochemistry and ELISA were used to investigate the relationship between SF S100A12 levels and synovitis levels in clinalclinical samples. In vitro cell experiments were conducted to investigate the effect of S100A12 on macrophage polarization. Public databases were utilized to predict and construct an S100A12-centered lncRNA-miRNA-mRNA competing endogenous RNA network, which was preliminarily validated using GEO datasets. Results The study outlines the protein profile in OA and non-OA SF. The results showed that the S100A12 level was significantly increased in OA SF and inflammatory chondrocytes. The OA synovium had more severe synovitis and higher levels of S100A12 than non-OA synovium. Exogenous S100A12 upregulated the levels of M1 markers and phosphorylated p65 and promoted p65 nuclear translocation, while pretreatment with BAY 11–7082 reversed these changes. It was also discovered that LINC00894 was upregulated in OA and significantly correlated with S100A12, potentially regulating S100A12 expression by acting as a miRNA sponge. Conclusions This study demonstrated that S100A12 promotes M1 macrophage polarization through the NF-κB pathway, and found that LINC00894 has the potential to regulate the expression of S100A12 as a therapeutic approach.

Inflammatory Knee Synovitis: Evaluation of an Accelerated FLAIR Sequence Compared With Standard Contrast-Enhanced Imaging.

The aim of this study was to assess the diagnostic value and accuracy of a deep learning (DL)-accelerated fluid attenuated inversion recovery (FLAIR) sequence with fat saturation (FS) in patients with inflammatory synovitis of the knee. Patients with suspected knee synovitis were retrospectively included between January and September 2023. All patients underwent a 3 T knee magnetic resonance imaging including a DL-accelerated noncontrast FLAIR FS sequence (acquisition time: 1 minute 38 seconds) and a contrast-enhanced (CE) T1-weighted FS sequence (acquisition time: 4 minutes 50 seconds), which served as reference standard. All knees were scored by 2 radiologists using the semiquantitative modified knee synovitis score, effusion synovitis score, and Hoffa inflammation score. Diagnostic confidence, image quality, and image artifacts were rated on separate Likert scales. Wilcoxon signed rank test was used to compare the semiquantitative scores. Interreader and intrareader reproducibility were calculated using Cohen κ. Fifty-five patients (mean age, 52 ± 17 years; 28 females) were included in the study. Twenty-seven patients (49%) had mild to moderate synovitis (synovitis score 6-13), and 17 patients (31%) had severe synovitis (synovitis score >14). No signs of synovitis were detected in 11 patients (20%) (synovitis score <5). Semiquantitative assessment of the whole knee synovitis score showed no significant difference between the DL-accelerated FLAIR sequence and the CE T1-weighted sequence (mean FLAIR score: 10.69 ± 8.83, T1 turbo spin-echo FS: 10.74 ± 10.32; P = 0.521). Both interreader and intrareader reproducibility were excellent (range Cohen κ [0.82-0.96]). Assessment of inflammatory knee synovitis using a DL-accelerated noncontrast FLAIR FS sequence was feasible and equivalent to CE T1-weighted FS imaging.

Blood flow velocity in the anterior humeral circumflex artery and tear size can predict synovitis severity in patients with rotator cuff tears.

Rotator cuff tears are often associated with synovitis, but the ability of noninvasive ultrasonography to predict the severity of synovitis remains unclear. We investigated whether ultrasound parameters, namely peak systolic velocity in the anterior humeral circumflex artery and Doppler activity in the glenohumeral joint and subacromial space, reflect synovitis severity. A total of 54 patients undergoing arthroscopic rotator cuff repair were selected. Doppler ultrasound was used to measure peak systolic velocity in the anterior humeral circumflex artery and Doppler activity in the glenohumeral joint and subacromial space, and these values were compared with the intraoperative synovitis score in univariate and multivariate analyses. Univariate analyses revealed that tear size, peak systolic velocity in the anterior humeral circumflex artery, and Doppler activity in the glenohumeral joint were associated with synovitis in the glenohumeral joint (P=0.02, P<0.001, P=0.02, respectively). In the subacromial space, tear size, peak systolic velocity in the anterior humeral circumflex artery, and Doppler activity in the subacromial space were associated with synovitis severity (P=0.02, P<0.001, P=0.02, respectively). Multivariate analyses indicated that tear size and peak systolic velocity in the anterior humeral circumflex artery were independently associated with synovitis scores in both the glenohumeral joint and the subacromial space (all P<0.05). These findings demonstrate that tear size and peak systolic velocity in the anterior humeral circumflex artery, which can both be measured noninvasively, are useful indicators of synovitis severity. Level of evidence: IV.

Role of Infrapatellar Fat Tissue in the Pathogenesis of Knee Osteoarthritis: A Review

Osteoarthritis (OA) is one of the most common joint diseases in the adult population. The role of indolent inflammation and predominance of catabolic cytokines over anabolic ones in OA has now been proven. The influence of obesity on the development of OA by releasing inflammatory mediators by fat tissue has been confirmed. Infrapatellar fat tissue (Hoffa’s fat pad) is a potential donor of proinflammatory cytokines, including specific fat tissue proinflammatory cytokines - adipokines. In a healthy person, infrapatellar fat tissue contributes to the distribution of mechanical load on the joint and metabolism of the synovial fluid. Infiltration of infrapatellar fat tissue by macrophages and lymphocytes leads not only to the production of proinflammatory cytokines with chondrolytic properties, but also to the maintenance of chronic inflammation in the synovial membrane, articular cartilage, and subchondral bone. Morphologic changes in Hoffa’s fat pad can be both an indicator of the inflammatory process in the joint cavity and a predictor of pathologic changes of the joint. Among histological changes, infiltration with macrophages and lymphocytes, fibrosis, thickening of the interlobular septa, reduction in the size of fat lobules and adipocytes, and increased vascularization are important for the course of OA. Morphologic changes can be assessed using a non-invasive method - magnetic resonance imaging, which makes it possible to evaluate the presence and severity of synovitis, thickening of the synovial membrane, edema, thickening of the interlobular septa, and a decrease in the volume of Hoffa’s fat pad. Histologic and tomographic signs can potentially be used to assess the severity of OA and develop prognostic scales. Infrapatellar fat tissue is also a source of mesenchymal stem cells phenotypically similar to chondrocytes, which can be used for regeneration of joint cartilage tissue with minimally invasive intervention to harvest them.

Clinical Implication of Glenohumeral and Subacromial Synovitis in Rotator Cuff Tears.

Synovitis of the glenohumeral (GH) joint and the subacromial (SA) space is commonly observed during arthroscopic rotator cuff surgery. To investigate the distribution, severity, and clinical implications of synovitis in the GH joint and SA space in patients with a full-thickness rotator cuff tear (RCT). Case series; Level of evidence, 4. Data were retrospectively collected from 207 patients with a full-thickness RCT who underwent arthroscopic repair. Preoperative parameters used in the clinical assessment included pain, range of motion (ROM), muscle strength, and functional scores. Macroscopic assessment of synovitis was performed intraoperatively in the 3 regions of interest (ROIs) of the GH joint and 4 ROIS of the SA space using an evaluation system. The distribution and severity of synovitis and the association between synovitis and clinical assessment were evaluated. Synovitis was more severe in the GH joint than in the SA space (P < .001). Synovitis in the posterior GH joint and the lateral SA space, where most of the rotator cuff was located, was the most severe area among the ROIs of the GH joint and the SA space, respectively (P < .05). All types of pain, except for pain at rest, were associated with synovitis in the posterior GH joint (P < .05). All ROM measures were associated with synovitis in the posterior and inferior GH joint (|r| > 0.20; P < .05 for both). The strength of the supraspinatus and the infraspinatus was associated with synovitis in the posterior GH joint (P < .05). Shoulder function was associated with synovitis in the posterior and inferior GH joint and more in the posterior GH joint (P < .05 for both). Synovitis in the SA space was not associated with any of the clinical parameters. Synovitis in the posterior GH joint was the most severe form of synovitis in the GH joint in patients with a full-thickness RCT. Synovitis in the posterior GH joint was closely associated with increased pain and decreased ROM, muscle strength, and functional score. Synovitis in the SA space was milder and not associated with any clinical parameters.

Intravenous Tranexamic Acid Improves Visual Clarity During Synovectomy in Patients Undergoing Arthroscopic Rotator Cuff Repair: A Double-Blind, Randomized Controlled Study

PurposeTo assess the effects of intravenous tranexamic acid (TXA) on visual clarity at various surgical stages and the correlation between severity of synovitis and bursitis and visual clarity in patients undergoing arthroscopic shoulder surgery under an interscalene brachial plexus block. MethodsThis double-blind, randomized controlled study included patients undergoing arthroscopic rotator cuff repair. The TXA group was injected 1000 mg of TXA intravenously, and the control group was administered the same volume in normal saline 10 min preoperatively. Visual clarity was rated according to a three-grade visual clarity scoring system from grade 1 (clear) to grade 3 (poor) at four surgical stages (I, intra-articular soft tissue procedure including synovectomy; II, acromioplasty; III, bursectomy; and IV, greater tuberoplasty). The primary outcome was arthroscopic visual clarity. The secondary outcomes were medications administered for hemodynamic stability, length of hospital stay, and thromboembolic events. ResultsAltogether, 63 patients were included in the study and they were divided into the TXA group comprising 32 patients and the control group comprising 31 patients. The TXA group showed significantly better visual clarity than the control group (1(1–2) vs 2(1–2), p=0.027) during stage I, but not during stages II–IV. Spearman correlation analysis revealed a significant correlation between synovitis and visual clarity grade during synovectomy (correlation coefficient, 0.393; p=0.001), but not between bursitis and visual clarity grade during bursectomy. Deep vein thrombosis and pulmonary embolism did not occur in either group. ConclusionsIntravenous TXA can improve visual clarity during intra-articular soft tissue procedures, including synovectomy. However, it does not have a significant effect during acromioplasty, bursectomy, and greater tuberoplasty. TXA can be used to improve visual clarity in patients with suspected severe synovitis. Level of EvidenceLevel I, randomized controlled trial

Sexual dimorphism of the synovial transcriptome underpins greater PTOA disease severity in male mice following joint injury

Osteoarthritis is a disease with sex-dependent prevalence and severity in both humans and animal models. We sought to elucidate sex differences in synovitis, mechanical sensitization, structural damage, bone remodeling, and the synovial transcriptome in the anterior cruciate ligament rupture (ACLR) mouse model of post-traumatic osteoarthritis (PTOA). Male and female 12-week-old C57/BL6J mice were randomized to Sham or noninvasive ACLR with harvests at 7d or 28d post-ACLR (n=9 per sex in each group - Sham, 7d ACLR, 28d ACLR). Knee hyperalgesia, mechanical allodynia, and intra-articular MMP activity (via intravital imaging) were measured longitudinally. Trabecular and subchondral bone remodeling and osteophyte formation were assessed by µCT. Histological scoring of PTOA and synovitis and anti-MMP13 immunostaining were performed. NaV1.8-Cre;tdTomato mice were used to document localization and sprouting of nociceptors. Bulk RNA-seq of synovium in Sham, 7d, and 28d post-ACLR, and contralateral joints (n=6 per group per sex) assessed injury-induced and sex-dependent gene expression. Male mice exhibited more severe joint damage at 7d and 28d and more severe synovitis at 28d, accompanied by 19% greater MMP activity, 8% lower knee hyperalgesia threshold, and 43% lower hindpaw withdrawal threshold in injured limbs compared to female injured limbs. Females had injury-induced catabolic responses in trabecular and subchondral bone, whereas males exhibited 133% greater normalized osteophyte volume relative to females and sclerotic remodeling of trabecular and subchondral bone. NaV1.8+ nociceptor sprouting in subchondral bone and medial synovium was induced by injury and comparable between sexes. RNA-seq of synovium demonstrated similar injury-induced transcriptomic programs between the sexes at 7d, but only female mice exhibited a transcriptomic signature indicative of synovial inflammatory resolution by 28d, whereas males had persistent pro-inflammatory, pro-fibrotic, pro-neurogenic, and pro-angiogenic gene expression. Male mice exhibited more severe overall joint damage and pain behavior after ACLR, which was associated with persistent activation of synovial inflammatory, fibrotic, and neuroangiogenic processes, implicating persistent synovitis in driving sex differences in murine PTOA.

Mesenchymal stem cells in synovial fluid increase in number in response to synovitis and display more tissue-reparative phenotypes in osteoarthritis

BackgroundSynovial fluid mesenchymal stem cells (SF-MSCs) originate in the synovium and contribute to the endogenous repair of damaged intra-articular tissues. Here, we clarified the relationship between their numbers and joint structural changes during osteoarthritis (OA) progression and investigated whether SF-MSCs had phenotypes favorable for tissue repair, even in an OA environment.MethodsPartial medial meniscectomy (pMx) and sham surgery were performed on both knees of rats. SF and knee joints were collected from intact rats and from rats at 2, 4, and 6 weeks after surgery. SF was cultured for 1 week to calculate the numbers of colony-forming cells and colony areas. Joint structural changes were evaluated histologically to investigate their correlation with the numbers and areas of colonies. RNA sequencing was performed for SF-MSCs from intact knees and knees 4 weeks after the pMx and sham surgery.ResultsColony-forming cell numbers and colony areas were greater in the pMx group than in the intact and sham groups and peaked at 2 and 4 weeks, respectively. Synovitis scores showed the strongest correlation with colony numbers (R = 0.583) and areas (R = 0.456). RNA sequencing revealed higher expression of genes related to extracellular matrix binding, TGF-β signaling, and superoxide dismutase activity in SF-MSCs in the pMx group than in the sham group.ConclusionThe number of SF-MSCs was most closely correlated with the severity of synovitis in this rat OA model. Tissue-reparative gene expression patterns were observed in SF-MSCs from OA knees, but not from knees without intra-articular tissue damage.

Role of high-temperature requirement serine protease A 2 in rheumatoid inflammation

BackgroundHigh-temperature requirement serine protease A 2 (HtrA2) is known to be involved in growth, unfolded protein response to stress, apoptosis, and autophagy. However, whether HtrA2 controls inflammation and immune response remains elusive.MethodsExpression of HtrA2 in the synovial tissue of patients was examined using immunohistochemistry and immunofluorescence staining. Enzyme-linked immunosorbent assay was used to determine the concentrations of HtrA2, interleukin-6 (IL-6), interleukin-8 (IL-8), chemokine (C-C motif) ligand 2 (CCL2), and tumor necrosis factor α (TNFα). Synoviocyte survival was assessed by MTT assay. For the downregulation of HtrA2 transcripts, cells were transfected with HtrA2 siRNA.ResultsWe found that the concentration of HtrA2 was elevated in rheumatoid arthritis (RA) synovial fluid (SF) than in osteoarthritis (OA) SF, and its concentrations were correlated with the number of immune cells in the RA SF. Interestingly, HtrA2 levels in the SF of RA patients were elevated in proportion to synovitis severity and correlated with the expression of proinflammation cytokines and chemokines, such as IL-6, IL-8, and CCL2. In addition, HtrA2 was highly expressed in RA synovium and primary synoviocytes. RA synoviocytes released HtrA2 when stimulated with ER stress inducers. Knockdown of HtrA2 inhibited the IL1β-, TNFα-, and LPS-induced release of proinflammatory cytokines and chemokines by RA synoviocytes.ConclusionHtrA2 is a novel inflammatory mediator and a potential target for the development of an anti-inflammation therapy for RA.

Identification of MYH9 as a key regulator for synoviocyte migration and invasion through secretome profiling

Objectives‘Invasive pannus’ is a pathological hallmark of rheumatoid arthritis (RA). This study aimed to investigate secretome profile of synovial fibroblasts of patients with RA (RA-FLSs), a major cell type comprising...

P130 Transcriptomic analysis of synovitis identifies inhibition of CXCL1 as a mechanism contributing to resolution of inflammatory arthritis under IL-27 control

Abstract Background/Aims Interleukin-27 (IL-27) regulates adaptive immune responses and is critical for the timely resolution of inflammation to restore tissue homeostasis. Studies have highlighted roles for IL-27 in limiting immune cell effector function, stromal cell responses and erosive joint pathology in clinical rheumatoid arthritis and experimental models of the disease. In the murine antigen-induced arthritis (AIA) model, IL-27 receptor-deficient (Il27ra-/-) mice develop severe synovitis associated with increased infiltration of synovial CD4+ T cells, development of synovial ectopic lymphoid-like structures and exacerbated cartilage and bone erosion. Similarly, mice with collagen-induced arthritis (CIA) administered IL-27 show improved joint pathology and reduced serum IFN-γ and IL-17 levels. Identifying mechanisms by which IL-27 regulates arthritis progression is key to understanding its therapeutic potential. Using RNA-sequencing of synovial tissue and joint-infiltrating CD4+ T cells we reveal that IL-27 regulates the magnitude of synovitis and genes in CD4+ T cells central to neutrophil recruitment. Methods Antigen-induced arthritis (AIA) was established in Il27ra-/- and wild-type control mice. RNA-sequencing was performed on whole synovial tissue and joint-infiltrating CD4+ T cells during the peak of joint inflammation and during the resolution of synovitis. Differentially expressed genes were interrogated by molecular pathway analysis and gene set enrichment analysis. CD4+ T cell culture assays, qPCR and ELISA were used to test and validate genes under IL-27 regulation. Results RNA-sequencing of whole synovial tissue revealed that pathways relating to CD4+ T cell and Th17 biology were significantly overrepresented in Il27ra-/- mice with AIA, consistent with a pathogenic role for these cells in inflammatory arthritis. Genes associated with neutrophil effector function (e.g. Elane, Padi4, Prtn3) and recruitment (e.g. Cxcl1, Cxcr2) were also highly expressed in Il27ra-/- synovium and was reflected in the increased number of Ly6G+CD11b+ neutrophils recovered from the joints of Il27ra-/- mice. In contrast to the transcriptomic analysis of inflamed synovial tissue, surprisingly RNA-sequencing of joint-infiltrating CD4+ T cells revealed that the expression of signature Th17 genes (e.g. Il17a, Il17f, Rorc) was comparable between WT and Il27ra-/- T cells. This implies that IL-27 predominantly regulates the magnitude of the joint CD4+ T cell infiltrate more than the effector characteristics of the infiltrating T cells. Differential gene expression analysis revealed heightened Cxcl1 expression in both whole synovial tissue and joint-infiltrating CD4+ T cells recovered from Il27ra-/- mice with AIA. CD4+ T cell differentiation cultures confirmed upregulation of Cxcl1 following T cell receptor activation and under Th1 polarizing conditions. Here, IL-27 suppressed the expression of CXCL1 at the mRNA and protein level. Conclusion Together, our data reveals a role for IL-27 in limiting CXCL1 expression in activated and joint-infiltrating CD4+ T cells, highlighting a novel mechanism by which IL-27 may integrate innate and adaptive arms of the immune response to regulate arthritis progression. Disclosure I. Burridge: None. S. Eastham: None. D.G. Hill: None. R. Andrews: None. B. Szomolay: None. N. Williams: None. S.A. Jones: None. G.W. Jones: None.

Combined femoral and acetabular version and synovitis are associated with dGEMRIC scores in people with femoroacetabular impingement (FAI) syndrome.

This study sought to explore, in people with symptoms, signs and imaging findings of femoroacetabular impingement (FAI syndrome): (1) whether more severe labral damage, synovitis, bone marrow lesions, or subchondral cysts assessed on magnetic resonance imaging(MRI) were associated with poorer cartilage health, and (2) whether abnormal femoral, acetabular, and/or combined femoral and acetabular versions were associated with poorer cartilage health. This cross-sectional study used baseline data from the 50 participants with FAI syndrome in the Australian FASHIoN trial (ACTRN12615001177549) with available dGEMRIC scans. Cartilage health was measured using delayed gadolinium-enhanced MRI of cartilage (dGEMRIC) score sampled at the chondrolabral junction on three midsagittal slices, at one acetabular and one femoral head region of interest on each slice, and MRI features were assessed using the Hip Osteoarthritis MRI Score. Analyses were adjusted for alpha angle and body mass index, which are known to affect dGEMRIC score. Linear regression assessed the relationship with thedGEMRIC score of (i) selected MRI features, and (ii) femoral, acetabular, and combined femoral and acetabular versions. Hips with more severe synovitis had worse dGEMRIC scores (partial η2 = 0.167, p = 0.020), whereas other MRI features were not associated. A lower combined femoral and acetabular version was associated with a better dGEMRIC score (partial η2 = 0.164, p = 0.021), whereas isolated measures of femoral and acetabular version were not associated. In conclusion, worse synovitis was associated with poorer cartilage health, suggesting synovium and cartilage may be linked to the pathogenesis of FAI syndrome. A lower combined femoral and acetabular version appears to be protective of cartilage health at the chondrolabral junction.

Temporomandibular Joint: Approach to the Intermediate Space by Triangulation With Transillumination Reference

Arthroscopy of the temporomandibular joint is a minimally invasive surgical procedure. Nowadays, 3 levels are described depending on the complexity. Level I involves a single puncture with an anterior irrigating needle for outflow. Level II involves a double puncture using triangulation in order to be able to perform minor operative maneuvers. Subsequently, it is possible to progress to Level III and perform more advanced techniques, through multiple punctures, involving the arthroscopic canula and 2 or more working cannulas. However, in cases of advanced degenerative pathology or re-arthroscopy, it is common to observe advanced fibrillation, severe synovitis, adhesions, or articular obliteration which makes conventional triangulation difficult. On these cases, we propose a simple and effective technique that facilitates approach to the intermediate space by means of triangulation with transillumination reference.