Inflammatory Joint Disorders Research Articles

Age Related Osteoarthritis: Regenerative Therapy, Synthetic Drugs, and Naturopathy to Combat Abnormal Signal Transduction

Introduction: Osteoarthritis (OA) is a common chronic inflammatory neurodegenerative joint disorder that causes disability among the geriatric population. It involves the loss of the articular cartilage that covers the end of a long bone thereby failing to prevent the friction between the joints. Method: The literature on the prevalence of OA and different risk factors like physical inactivity, obesity, and joint injury was searched through Google scholar, PubMed, research gate, Wikipedia, etc for the review. Result: OA has affected around 303 million people globally. It affects the knee, hip, hands, and spine joints owing to common symptoms like pain, swelling, and disability. Further, OA-associated disability causes depression leading to an economic and social burden with physical isolation, thus making it more severe for older people in their day-to-day lifestyle. Presently, no permanent cure has been devel-oped for OA. Although, there are many risk factors of OA, among them, the most prominent one is considered to be “aging”. Most people crossing the age of 65–70 years have been associated with changes in the joints (one or more) about the development of OA. Several theories related to cellular aging and cell senescence with OA development. However, aging alone does not cause this condition; it is accelerated by the abnormal signal transduction followed by the progression of OA. The blueprint of possible management of OA by the different approaches has been the prime concern of this review work. Conclusion: An outline of the risk factors of abnormal signal transduction and different treatment ap-proaches, including regenerative therapy, synthetic drugs, and naturopathy manipulating them concern-ing OA are discussed in this review which might be an answer to the age-old issue of geriatrics.

MiR-124-3p sabotages lncRNA MALAT1 stability to repress chondrocyte pyroptosis and relieve cartilage injury in osteoarthritis

BackgroundOsteoarthritis (OA) is a prevalent inflammatory joint disorder. microRNAs (miRNAs) are increasingly involved in OA.AimOur study is proposed to clarify the role of miR-124-3p in chondrocyte pyroptosis and cartilage injury in OA.MethodsOA mouse model was established via the treatment of destabilization of the medial meniscus (DMM), and the in vitro cell model was also established as mouse chondrocytes were induced by lipopolysaccharide (LPS). Mouse cartilage injury was assessed using safranin-O-fast green staining, hematoxylin–eosin staining, and OARSI grading method. Expressions of miR-124-3p, MALAT1, KLF5, and CXCL11 were determined. Cartilage injury (MMP-13, osteocalcin), inflammation (IL-6, IL-2, TNF-, IL-1β, and IL-18)- and pyroptosis-related factors (Cleaved Caspase-1 and GSDMD-N) levels were detected. Mechanically, MALAT1 subcellular localization was confirmed. The binding relationships of miR-124-3p and MALAT1 and MALAT1 and KLF5 were verified. MALAT1 half-life period was detected. Then, miR-124-3p was overexpressed using agomiR-124-3p to perform the rescue experiments with oe-MALAT1 or oe-CXCL11.ResultsmiR-124-3p was downregulated in DMM mice and LPS-induced chondrocytes where cartilage injury, and increased levels of inflammation- and pyroptosis-related factors were found. miR-124-3p overexpression relieved cartilage injury and repressed chondrocyte pyroptosis. miR-124-3p bounds to MALAT1 to downregulate its stability and expression, and MALAT1 bounds to KLF5 to enhance CXCL11 transcription. Overexpression of MALAT1 or CXCL11 annulled the repressive function of miR-124-3p in chondrocyte pyroptosis.ConclusionmiR-124-3p reduced MALAT1 stability and inhibited the binding of MALAT1 and KLF5 to downregulate CXCL11, thereby suppressing chondrocyte pyroptosis and cartilage injury in OA.

Celastrol inhibits rheumatoid arthritis by inducing autophagy via inhibition of the PI3K/AKT/mTOR signaling pathway

ObjectiveRheumatoid arthritis (RA) is a chronic autoimmune inflammatory disorder of the synovial joints. Celastrol (Cel) is a quinone-methylated triterpenoid extracted from Tripterygium wilfordii Hook F (TwHF) that has been proven to be effective in treating RA. However, the underlying molecular mechanism of celastrol in the treatment of RA remains unknown. This study explored the protective effect of celastrol against RA and the specific mechanisms of celastrol in vitro and in vivo. MethodsA chicken type II collagen (CII)-induced arthritis (CIA) mouse model was used to explore the anti-arthritic effects of celastrol, and paw swelling degree, the poly-arthritis index score and serum cytokine levels were determined. Pathological morphology was observed using hematoxylin and eosin (H&E) staining. The influences of celastrol on the proliferation of tumor necrosis factor-α (TNF-α)-induced fibroblast-like synoviocytes (FLSs) were tested by Cell Counting Kit-8 (CCK-8) assays and5-ethynyl-2′-deoxyuridine (EdU) staining assays. The level of autophagy was detected by transmission electron microscopy (TEM). Furthermore, the PI3K/AKT/mTOR pathway and the status of autophagy in the CIA model and FLSs were also detected by western blot and immunofluorescence staining. ResultsThe results showed that celastrol decreased arthritis severity and inhibited TNF-α-induced FLSs proliferation. Additionally, celastrol decreased the secretion of pro-inflammatory cytokines. Moreover, celastrol increased autophagosome levels and LC3B protein expression in TNF-α-treated FLSs. Furthermore, celastrol increased the protein expression of LC3-II and Beclin-1 and decreased the phosphorylation degree of mTOR and AKT. ConclusionIn conclusion, our findings confirmed that celastrol ameliorates RA via the up-regulation of autophagy by inhibiting the PI3K/AKT/mTOR axis.

Adipose-Derived Stem Cell Exosomes as a Novel Anti-Inflammatory Agent and the Current Therapeutic Targets for Rheumatoid Arthritis.

Patients with rheumatoid arthritis (RA), a chronic inflammatory joint disorder, may not respond adequately to current RA treatments. Mesenchymal stem cells (MSCs) elicit several immunomodulatory and anti-inflammatory effects and, thus, have therapeutic potential. Specifically, adipose-derived stem cell (ADSC)-based RA therapy may have considerable potency in modulating the immune response, and human adipose tissue is abundant and easy to obtain. Paracrine factors, such as exosomes (Exos), contribute to ADSCs’ immunomodulatory function. ADSC-Exo-based treatment can reproduce ADSCs’ immunomodulatory function and overcome the limitations of traditional cell therapy. ADSC-Exos combined with current drug therapies may provide improved therapeutic effects. Using ADSC-Exos, instead of ADSCs, to treat RA may be a promising cell-free treatment strategy. This review summarizes the current knowledge of medical therapies, ADSC-based therapy, and ADSC-Exos for RA and discusses the anti-inflammatory properties of ADSCs and ADSC-Exos. Finally, this review highlights the expanding role and potential immunomodulatory activity of ADSC-Exos in patients with RA.

Role of BLACAT1 in IL-1β-Induced Human Articular Chondrocyte Apoptosis and Extracellular Matrix Degradation via the miR-149-5p/ HMGCR Axis.

Osteoarthritis (OA) is an inflammatory joint disorder with high incidence rates. Long non-coding RNAs (LncRNAs) influence OA development. In this research, we attempt to figure out the functions of lncRNA BLACAT1 in human articular chondrocyte (HAC) apoptosis and extracellular matrix (ECM) degradation in OA. Interleukin (IL)-1β was employed to induce HAC damage. Cell viability and apoptosis were detected, with expression patterns of lncRNA BLACAT1, miR-149-5p, and HMGCR, and levels of Caspase-3, Caspase-9, BAX, Bcl-2, COL2A1, and SOX9 determined. Then, lncRNA BLACAT1 was silenced in IL-1β-treated HACs to analyze its role in HAC damage. The target relations of lncRNA BLACAT1 and miR-149-5p and miR-149-5p and HMGCR were verified. In addition, combined experiments were performed as a miR-149-5p inhibitor or HMGCR overexpression was injected into cells with lncRNA BLACAT1 silencing. In IL-1β-treated HACs, lncRNA BLACAT1 and HMGCR were overexpressed while miR- 149-5p was poorly expressed, along with reduced cell viability, enhanced apoptosis, elevated Caspase-3 and Caspase-9 activities, increased BAX level, decreased Bcl-2 level, and declined levels of COL2A1 and SOX9, which were reversed by lncRNA BLACAT1 silencing. LncRNA BLACAT1 targeted miR-149-5p, and miR-149-5p targeted HMGCR. miR-149-5p knockout or HMGCR overexpression annulled the inhibitory role of lncRNA BLACAT1 silencing in HAC apoptosis and ECM degradation. LncRNA BLACAT1 was overexpressed in IL-1β-treated HACs, and the lncRNA BLACAT1/miR-149-5p/HMGCR ceRNA network promoted HAC apoptosis and ECM degradation.

Pro and contra: is synovitis, acne, pustulosis, hyperostosis, and osteitis (SAPHO) a spondyloarthritis variant?

The purpose of this review is to present the up-to-date evidence on the epidemiology, pathogenesis, musculoskeletal manifestations, and imaging of the synovitis, acne, pustulosis, hyperostosis, and osteitis (SAPHO) syndrome and to discuss its relationship with spondyloarthritis (SpA). SAPHO is a rare inflammatory disorder of bone, joints, and skin, with a worldwide distribution that predominantly affects the middle-age adults. The hallmark of the syndrome is a constellation of sterile inflammatory osteitis, hyperostosis, and synovitis involving the anterior chest wall, associated with acneiform and neutrophilic dermatoses, such as palmoplantar pustulosis and severe acne. The axial skeleton, sacroiliac, and peripheral joints can be involved in a similar fashion to SpA. The pathogenesis of the syndrome is multifactorial. The diagnosis is mainly based on the clinical and typical radiological features. The treatment approach is based on the off-label use of antibiotics, bisphosphonates, disease-modifying antirheumatic drugs, and anticytokine biologics. The SAPHO syndrome shares common features with SpA-related diseases, yet also shows some unique pathogenetic and clinical features. The nosology of SAPHO remains a subject of controversy, awaiting further research into the pathogenetic and clinical aspects of this syndrome. A better understanding of these aspects will improve the diagnostics and clinical care of patients with SAPHO.

Engineering approaches to investigate the roles of lymphatics vessels in rheumatoid arthritis.

Rheumatoid arthritis (RA) is one of the most common chronic inflammatory joint disorders. While our understanding of the autoimmune processes that lead to synovial degradation has improved, a majority of patients are still resistant to current treatments and require new therapeutics. An understudied and promising area for therapy involves the roles of lymphatic vessels (LVs) in RA progression, which has been observed to have a significant effect on mediating chronic inflammation. RA disease progression has been shown to correlate with dramatic changes in LV structure and interstitial fluid drainage, manifesting in the retention of distinct immune cell phenotypes within the synovium. Advances in dynamic imaging technologies have demonstrated that LVs in RA undergo an initial expansion phase of increased LVs and abnormal contractions followed by a collapsed phase of reduced lymphatic function and immune cell clearance in vivo. However, current animal models of RA fail to decouple biological and biophysical factors that might be responsible for this lymphatic dysfunction in RA, and a few attempted in vitro models of the synovium in RA have not yet included the contributions from the LVs. Various methods of replicating LVs in vitro have been developed to study lymphatic biology, but these have yet not been integrated into the RA context. This review discusses the roles of LVs in RA and the current engineering approaches to improve our understanding of lymphatic pathophysiology in RA.

Prevalence and characteristics of systemic conditions in patients undergoing orthognathic surgery: a retrospective study

The aim of this study was to investigate the prevalence and characteristics of systemic conditions in patients undergoing orthognathic surgery at a tertiary centre. Ninety of the 838 patients undergoing orthognathic surgery between 2013 and 2019 had a systemic condition (prevalence of 10.7%). The most prevalent categories of systemic conditions were inflammatory joint disorders, endocrinological disorders, and syndromes. Patients with syndromes were significantly younger at the time of surgery than patients with endocrinological (P < 0.001), inflammatory joint (P = 0.003), or gastrointestinal disorders (P = 0.033). Endocrinological disorders, syndromes, and malignancies were more frequently associated with a skeletal class III malocclusion (P = 0.009, P < 0.001, and P = 0.048 respectively). Further research is needed to clarify the role of systemic conditions in the aetiology of malocclusion and postoperative outcomes.

Kirenol: A Potential Natural Lead Molecule for a New Drug Design, Development, and Therapy for Inflammation.

Kirenol, a potential natural diterpenoid molecule, is mainly found in Sigesbeckia species. Kirenol has received a lot of interest in recent years due to its wide range of pharmacological actions. In particular, it has a significant ability to interact with a wide range of molecular targets associated with inflammation. In this review, we summarise the efficacy and safety of kirenol in reducing inflammation, as well as its potential mechanisms of action and opportunities in future drug development. Based on the preclinical studies reported earlier, kirenol has a good therapeutic potential against inflammation involved in multiple sclerosis, inflammatory bowel disorders, diabetic wounds, arthritis, cardiovascular disease, bone damage, and joint disorders. We also address the physicochemical and drug-like features of kirenol, as well as the structurally modified kirenol-derived molecules. The inhibition of pro-inflammatory cytokines, reduction in the nuclear factor kappa-B (NF-κB), attenuation of antioxidant enzymes, stimulation of heme-oxygenase-1 (HO-1) expression, and nuclear factor erythroid 2-related factor 2 (Nrf2) phosphorylation are among the molecular mechanisms contributing to kirenol’s anti-inflammatory actions. Furthermore, this review also highlights the challenges and opportunities to improve the drug delivery of kirenol for treating inflammation. According to the findings of this review, kirenol is an active molecule against inflammation in numerous preclinical models, indicating a path to using it for new drug discovery and development in the treatment of a wide range of inflammations.

A computational model revealing the immune-related hub genes and key pathways involved in rheumatoid arthritis (RA).

Rheumatoid arthritis (RA) has one of the highest disability rates among inflammatory joint disorders. However, the reason and possible molecular events are still unclear. There are various treatment options available, but no complete cure. To obtain early diagnosis and successful medication in RA, it is necessary to explore gene susceptibility and pathogenic factors. The main intend of our work is to explore the immune-related hub genes with similar functions that are differentially expressed in RA patients. Three datasets such as GSE21959, GSE55457, and GSE77298, were taken to analyze the differently expressed genes (DEGs) among 55 RA and 33 control samples. We obtained 331 upregulated and 275 downregulated DEGs from three Gene Expression Omnibus (GEO) datasets using the R package. Furthermore, a protein-protein interaction network was built for upregulated and downregulated DEGs using Cytoscape. Subsequently, MCODE analysis was performed and obtained the top two modules in each DEG's upregulated and downregulated protein-protein interactions (PPIs) network. CytoNCA and cytoHubba were performed and identified overlapping DEGs. In addition, we narrowed down DEGs by filtering with immune-related genes and identified DE-IRGs. Gene ontology (GO) and KEGG pathway analysis in upregulated and downregulated DEGs were executed with the DAVID platform. Our study obtained the nine most significant DE-IRGs in RA such as CXCR4, CDK1, BUB1, BIRC5, AGTR1, EGFR, EDNRB, KALRN, and GHSR. Among them, CXCR4, CDK1, BUB1, and BIRC5 are overexpressed in RA and may contribute to the pathophysiology of the disease. Similarly, AGTR1, EGFR, EDNRB, KALRN, and GHSR are all low expressed in RA and may have a contribution to pathogenesis. GO, KEGG functional enrichment, and GeneMANIA showed that the dysregulated process of DE-IRGs causes RA development and progression. These findings may be helpful in future studies in RA diagnosis and therapy.

β-arrestin-2 alleviates rheumatoid arthritis injury by suppressing NLRP3 inflammasome activation and NF- κB pathway in macrophages

ABSTRACT Rheumatoid arthritis (RA) is a chronic inflammatory joint disorder that inflicts damage to the joints of the hands and wrist. The aim of this study was to investigate the protective effect of β-Arrestin-2 (βArr2) on RA in vivo and in vitro. The βArr2 adenovirus (βArr2-Ad) or the control (Con-Ad) was injected into the ankle joint cavity of collagen-induced arthritis (CIA) mice. According to the results, an improvement was shown in the symptoms and pathological injury of RA after an upregulation of βArr2. Correspondingly, the inflammatory response was attenuated, as evidenced by the decreased serum pro-inflammatory cytokines levels and NF-κB pathway-related proteins. Nucleotide-binding domain leucine-rich repeat and pyrin domain containing receptor 3 (NLRP3) inflammasome activation was inhibited in CIA mice treated with βArr2-Ad injection, as reflected by the diminished IL-18 level and declined protein levels of inflammasome components in the ankle joint. Likewise, the anti-inflammatory effect of macrophages was also validated by in vitro experiments. In summary, βArr2 effectively ameliorates ankle inflammation in CIA mice via NF-κB/NLRP3 inflammasome, providing theoretical and clinical basis for RA therapy.

Evaluation of the Ankylosing Spondylitis Transcriptome for Oxidative Phosphorylation Pathway: The Shared Pathway with Neurodegenerative Diseases.

Ankylosing spondylitis (AS) is a systemic inflammatory disorder of joints and entheses. Recent studies have reported an increased prevalence of dementia in AS patients. However, data for exploring the association between dementia and AS remain uncertain. In this study, enriched pathways and differentially expressed genes (DEGs) were identified in whole blood transcription data of AS patients obtained from the gene expression omnibus (GEO) database; using gene set enrichment analysis (GSEA) and differential expression analysis. Four pathways, including oxidative phosphorylation, Alzheimer's, Parkinson's, and Huntington's diseases were significantly enriched in AS patients compared to the controls. We identified 22 common genes among the pathways that showed an increasing trend in AS compared to the controls. Five of them including COX7B, NDUFB3, ATP5PF, UQCRB, and NDUFS4 were the most significant genes which were selected for gene expression analysis; using real-time PCR on RNA contents of peripheral blood mononuclear cells (PBMCs) of AS patients and controls (20 samples from each group). The gene expression analysis indicated considerable overexpression of COX7B (p<0.0001) and ATP5J (p=0.0001) genes in AS patients group in comparison to the control samples. The role of oxidative phosphorylation has previously been established in dementia pathogenesis. Given that AS patients have also a remarkably higher prevalence of dementia than the their healthy counterparts, hence our results may propose that the common pathway of oxidative phosphorylation can be regarded as a possible shared contributing factor in the etiopathogenesis of AS and dementia.

Pro-regenerative Dialogue Between Macrophages and Mesenchymal Stem/Stromal Cells in Osteoarthritis.

Osteoarthritis (OA), the most common degenerative and inflammatory joint disorder, is multifaceted. Indeed, OA characteristics include cartilage degradation, osteophytes formation, subchondral bone changes, and synovium inflammation. The difficulty in discovering new efficient treatments for OA patients up to now comes from the adoption of monotherapy approaches targeting either joint tissue repair/catabolism or inflammation to address the diverse components of OA. When satisfactory, these approaches only provide short-term beneficial effects, since they only result in the repair and not the full structural and functional reconstitution of the damaged tissues. In the present review, we will briefly discuss the current therapeutic approaches used to repair the damaged OA cartilage. We will highlight the results obtained with cell-based products in clinical trials and demonstrate how the current strategies result in articular cartilage repair showing restricted early-stage clinical improvements. In order to identify novel therapeutic targets and provide to OA patients long-term clinical benefits, herein, we will review the basis of the regenerative process. We will focus on macrophages and their ambivalent roles in OA development and tissue regeneration, and review the therapeutic strategies to target the macrophage response and favor regeneration in OA.

Metabolomics Reveals the Mechanisms for the Pulmonary Toxicity of Siegesbeckia orientalis L. and the Toxicity-Reducing Effect of Processing.

Siegesbeckia orientalis L. (SO) is a commonly used Chinese medicinal herb. It has long been used as a remedy in traditional Chinese medicine (TCM) for symptoms that resemble inflammatory joint disorders. However, it is slightly toxic. According to the TCM theory, processing can reduce the toxicity of the herbs. Here, we performed metabolomics to determine whether processing with rice wine reduces the toxicity of raw SO, and to explore the mechanisms underlying the raw SO–induced toxicity and the toxicity-reducing effect of processing. Our results showed that raw SO has long-term toxicity in rats. It significantly elevated the serum level of LDH and caused histopathological damages in the lung tissues. It is worth noting that the LDH level in the PSO group was lower than that in the raw SO group, and the damages in lung tissues were relatively mild in PSO-treated rats, suggesting that processing reduces the pulmonary toxicity of the raw. Moreover, a total of 32 significantly changed metabolites were identified. Based on the MetaboAnalyst pathway analysis, we found that two characteristic metabolic pathways including alanine, aspartate and glutamate metabolism and glycerophospholipid metabolism were only changed in the raw SO group, while histidine metabolism was only changed in the PSO group, which suggests that induction of oxidative stress contributes to raw SO–induced pulmonary toxicity, and free radical scavenging might be responsible for the toxicity-reducing effect of processing. Our data shed new light on how raw SO induces pulmonary toxicity and how the toxicity can be reduced by processing. This study not only provides scientific justifications for the traditional processing theory of SO, but also helps to optimize the processing protocol and the clinical drug combination of SO.

Lasp1 regulates adherens junction dynamics and fibroblast transformation in destructive arthritis

The LIM and SH3 domain protein 1 (Lasp1) was originally cloned from metastatic breast cancer and characterised as an adaptor molecule associated with tumourigenesis and cancer cell invasion. However, the regulation of Lasp1 and its function in the aggressive transformation of cells is unclear. Here we use integrative epigenomic profiling of invasive fibroblast-like synoviocytes (FLS) from patients with rheumatoid arthritis (RA) and from mouse models of the disease, to identify Lasp1 as an epigenomically co-modified region in chronic inflammatory arthritis and a functionally important binding partner of the Cadherin-11/β-Catenin complex in zipper-like cell-to-cell contacts. In vitro, loss or blocking of Lasp1 alters pathological tissue formation, migratory behaviour and platelet-derived growth factor response of arthritic FLS. In arthritic human TNF transgenic mice, deletion of Lasp1 reduces arthritic joint destruction. Therefore, we show a function of Lasp1 in cellular junction formation and inflammatory tissue remodelling and identify Lasp1 as a potential target for treating inflammatory joint disorders associated with aggressive cellular transformation.

In vivo nano contrast-enhanced photoacoustic imaging for dynamically lightening the molecular changes of rheumatoid arthritis

Rheumatoid arthritis (RA) is one of the most prevalent inflammatory joint disorders. Early diagnosis, accurate staging, and imaging guided treatment response of RA remain crucial clinical significances for improving treatment outcomes. In this study, we introduced endogenous melanin nanoparticles (MNPs) conjugated with Cyclic Arg-Gly-Asp (RGD) peptide (MNP-PEG-RGD) as a contrast agent for accurate photoacoustic imaging (PAI) of RA diagnosis. It was observed that the prepared nanoprobes had favorable PA sensitivity, photostability and biocompatibility. In vivo studies using RA mouse model revealed that this nanoprobe could target αvβ3 actively at 1 h post-injection, while the signal was remarkably increased in the arthritic joint which could earlier diagnose RA than conventional imaging system. It was of crucial importance to staging RA by PAI with significant difference in nanoprobes accumulation. Furthermore, we tracked the therapeutic efficacy of etanercept in RA treatment by PAI. The observed advancement of arthritis on the PAI was confirmed by histological and immunohistochemical analysis. In conclusion, this study shed light on the development of innovative multifunctional theranostic nanoplatform for both RA monitoring and treatment with a promising future in clinical translation.

OP0089 DO PAIN CATASTROPHIZING REDUCE THE LIKELIHOOD OF REMISSION IN PATIENTS WITH CHRONIC INFLAMMATORY JOINT DISORDERS?

Background:Rheumatoid arthritis (RA), psoriatic arthritis (PsA) and axial spondyloarthritis (ax-SpA) may have a devastating impact on patients’ lives, including chronic and relapsing pain. One factor contributing to bio-psycho-social model of pain in these diseases, is pain catastrophizing (PC) defined as tendency to report pain experience in exaggerated terms, to ruminate more or to feel helpless about it. In one RA study PC has been shown to be associated with patient reported outcomes e.g. reduced likelihood of remission using composite measures.[1]Objectives:Main objective of this study was to explore if pain catastrophizing score is associated with remission rates in the chronic inflammatory joint disorders RA, PsA and ax-SpA.Methods:Patients were recruited during routine assessment at an outpatient clinic in Norway. Variables collected included demographics, treatment, disease duration, global pain VAS, pain catastrophizing score (PCS), and disease activity scores: DAS28-CRP for RA, BASDAI for ax-SpA and DAPSA for PsA. Cut off definitions of remission was for DAS28 &lt;2.6, for BASDAI &lt;4.0 and for DAPSA ≤4.0. Two questions from Coping Strategies Questionnaire as recommended by Jensen et al [2] were used to describe PC, range PC total score (PCS) 0–6. Patients with PCS ≥ 4 were defined as high pain catastrophizers. Statistics included Chi-Square test and adjusted logistic regression (enter procedure).Results:For RA (N=580), PsA (N=394) and ax-SpA (N=225) mean age (SD) was 61.5 (13.1), 54.4 (12.9) and 47.5 (12.9) years, mean disease duration 12.6 (10.9), 10.2 (8.4) and 12.2 (10.7) years and percentage of women 66.7%, 47.0% and 38.4%. Mean (SD) DAS28-CRP in RA was 2.3 (1.0), BASDAI for ax-SpA 3.7 (2.3) and DAPSA for PsA 10.8 (8.5). Mean (SD) global pain (VAS 0-100mm) was for RA 32.0 (25.6), for PsA 35.5 (25.4) and for ax-SpA 39.4 (25.4) mm. Conventional synthetic DMARDs were used by 65.0% of RA patients, 54.8% by PsA and 9.8% in ax-SpA and for biologic DMARDs the corresponding numbers were 36.7%, 43.9%, 65.9%, respectively.Percentage of patients in remission was significantly lower in high pain catastrophizers compared with low pain catastrophizers in RA (34.1% vs 70.3%, p&lt;0.01) and ax-SpA patients (17.9% vs 64.5%, p&lt;0.01) but not in PsA (10.3% vs 26.7%, p=0.06).In analysis adjusting for age, gender, disease duration and global pain (Tab. 1), PC was independently associated with lower remission rate in RA (OR 0.79 (95% CI 0.63, 0.99), p=0.04) and in ax-SpA (OR 0.65 (95% CI 0.46, 0.93), p=0.02) but not in PsA (OR 0.83 (95% CI 0.55, 1.25), p=0.37)Conclusion:Our data indicates that high level of patient’s PC may reduce likelihood of achieving remission in RA and ax-SpA. Interestingly, this was not shown in PsA patients. Further studies are needed to reveal the importance of PC and its influence on composite disease activity measures used to define disease status e.g. remission.Table 1.Variables and their associations with remission rates in RA, PsA, ax-SpA in logistic regression analysis.RA remissionPsA remissionax-SpA remissionOR (95%CI)pOR (95%CI)pOR (95%CI)pPCS0.79 (0.63, 0.99)0.040.83 (0.55, 1.25)0.370.65 (0.46, 0.93)0.02Age0.99 (0.97, 1.01)0.171.00 (0.96, 1.04)0.850.98 (0.94, 1.02)0.27Gender0.87 (0.52, 1.45)0.590.37 (0.15, 0.93)0.030.92 (0.40, 2.14)0.85Disease duration1.03 (1.00, 1.05)0.030.95 (0.90, 1.00)0.061.04 (0.99, 1.09)0.09Global pain (VAS)0.96 (0.95, 0.97)&lt;0.010.85 (0.81, 0.89)&lt;0.010.90 (0.88, 0.92)&lt;0.01

Trajectories of disease courses in the inception cohort of newly diagnosed patients with JIA (ICON-JIA): the potential of serum biomarkers at baseline

ObjectiveJuvenile idiopathic arthritis (JIA) is a heterogeneous group of inflammatory joint disorders with a chronic-remitting disease course. Treat-to-target approaches have been proposed but monitoring disease activity and predicting the response to treatment remains challenging.MethodsWe analyzed biomarkers and their relationship to outcome within the first year after JIA diagnosis in the German Inception Cohort of Newly diagnosed patients with JIA (ICON-JIA). CRP, CXCL9, CXCL10, CXCL11, erythrocyte sedimentation rate, G-CSF, IL-6, IL-17A, IL-18, MCP-1, MIP-1α, MMP-3, S100A8/A9, S100A12, TNFα, and TWEAK were measured at baseline and 3 months later.ResultsTwo-hundred-sixty-six JIA patients with active disease at baseline were included, with oligoarthritis and rheumatoid factor-negative polyarthritis representing the most frequent categories (72.9%). Most biomarkers were elevated in JIA compared to healthy pediatric controls. Patients with systemic JIA had higher CRP, S100A8/A9 and S100A12 levels compared to other JIA categories. Baseline levels of TWEAK, G-CSF and IL-18 were lower in oligoarthritis patients with disease extension within 1 year. Increased baseline levels of CRP, S100A8/A9, S100A12 and ESR were associated with the subsequent addition of biologic disease-modifying antirheumatic drugs (DMARDs). Higher baseline ESR, G-CSF, IL-6, IL-17A and TNF levels indicated an increased risk for ongoing disease activity after 12 months.ConclusionOur data demonstrate that elevated baseline levels of CRP, S100A8/A9 and S100A12 as well as increased ESR are associated with the necessity to escalate therapy during the first 12 month of follow-up. Furthermore, biomarkers related to Th17 activation may inform on future disease course in previously treatment-naïve JIA patients.

Pharmacological screening of ethanolic extract of Pithecellobium dulce for antiarthritic activity in Rats

Arthritis is an inflammatory joint disorder in which cartilage of the joint is gradually lost and categorized by swelling of joints, pain, and loss of function. The present study was conducted to explore the antiarthritic activity of ethanolic extract of Pithecellobium dulce against formaldehyde induced at sub plantar region of the left hind paw during days 1 and 3 of the study period. The changes observed in paw diameter during the study period, various biochemical, and haematological parameters were monitored. The Radiographic analysis and histopathology significantly improved after treatment with test extract P. dulce (250 mg/kg, b.w., p.o. ) as compared to the standard treatment with indomethacin (10 mg/kg, b.w., p.o. ).The results of the current investigation concluded that ethanolic extract of P. dulce possesses significant anti-arthritic activity against formaldehyde induced arthritis model, justifying its therapeutic role in arthritic conditions. The observed antiarthritic activity may be due to the presence of phytoconstituents such as alkaloids and flavonoids. P. dulce significantly suppressed the paw oedema in formaldehyde models ( P &lt;0.001). The Histopathological and radiographic studies of joints also showed a protective effect of P. dulce .

The Role of Chronic Inflammatory Bone and Joint Disorders in the Pathogenesis and Progression of Alzheimer's Disease.

Late-onset Alzheimer's Disease (LOAD) is a devastating neurodegenerative disorder that causes significant cognitive debilitation in tens of millions of patients worldwide. Throughout disease progression, abnormal secretase activity results in the aberrant cleavage and subsequent aggregation of neurotoxic Aβ plaques in the cerebral extracellular space and hyperphosphorylation and destabilization of structural tau proteins surrounding neuronal microtubules. Both pathologies ultimately incite the propagation of a disease-associated subset of microglia—the principle immune cells of the brain—characterized by preferentially pro-inflammatory cytokine secretion and inhibited AD substrate uptake capacity, which further contribute to neuronal degeneration. For decades, chronic neuroinflammation has been identified as one of the cardinal pathophysiological driving features of AD; however, despite a number of works postulating the underlying mechanisms of inflammation-mediated neurodegeneration, its pathogenesis and relation to the inception of cognitive impairment remain obscure. Moreover, the limited clinical success of treatments targeting specific pathological features in the central nervous system (CNS) illustrates the need to investigate alternative, more holistic approaches for ameliorating AD outcomes. Accumulating evidence suggests significant interplay between peripheral immune activity and blood-brain barrier permeability, microglial activation and proliferation, and AD-related cognitive decline. In this work, we review a narrow but significant subset of chronic peripheral inflammatory conditions, describe how these pathologies are associated with the preponderance of neuroinflammation, and posit that we may exploit peripheral immune processes to design interventional, preventative therapies for LOAD. We then provide a comprehensive overview of notable treatment paradigms that have demonstrated considerable merit toward treating these disorders.