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ID PMID Title PublicationDate abstract
27492386 Microbiota and chronic inflammatory arthritis: an interwoven link. 2016 Aug 4 BACKGROUND: Only recently, the scientific community gained insights on the importance of the intestinal resident flora for the host's health and disease. Gut microbiota in fact plays a crucial role in modulating innate and acquired immune responses and thus interferes with the fragile balance inflammation versus tolerance. MAIN BODY: Correlations between gut bacteria composition and the severity of inflammation have been studied in inflammatory bowel diseases. More recently similar alterations in the gut microbiota have been reported in patients with spondyloarthritis, whereas in rheumatoid arthritis an accumulating body of evidence evokes a pathogenic role for the altered oral microbiota in disease development and course. In the context of dysbiosis it is also important to remember that different environmental factors like stress, smoke and dietary components can induce strong bacterial changes and consequent exposure of the intestinal epithelium to a variety of different metabolites, many of which have an unknown function. In this perspective, and in complex disorders like autoimmune diseases, not only the genetic makeup, sex and immunologic context of the individual but also the structure of his microbial community should be taken into account. CONCLUSIONS: Here we provide a review of the role of the microbiota in the onset, severity and progression of chronic inflammatory arthritis as well as its impact on the therapeutic management of these patients. Furthermore we point-out the complex interwoven link between gut-joint-brain and immune system by reviewing the most recent data on the literature on the importance of environmental factors such as diet, smoke and stress.
27158677 Proresolving and cartilage-protective actions of resolvin D1 in inflammatory arthritis. 2016 Apr 21 Rheumatoid arthritis (RA) is a debilitating disease characterized by persistent accumulation of leukocytes within the articular cavity and synovial tissue. Metabololipidomic profiling of arthritic joints from omega-3 supplemented mice identified elevated levels of specialized proresolving lipid mediators (SPM) including resolvin D1 (RvD1). Profiling of human RA synovial fluid revealed physiological levels of RvD1, which - once applied to human neutrophils - attenuated chemotaxis. These results prompted analyses of the antiarthritic properties of RvD1 in a model of murine inflammatory arthritis. The stable epimer 17R-RvD1 (100 ng/day) significantly attenuated arthritis severity, cachexia, hind-paw edema, and paw leukocyte infiltration and shortened the remission interval. Metabololipidomic profiling in arthritic joints revealed 17R-RvD1 significantly reduced PGE(2) biosynthesis, while increasing levels of protective SPM. Molecular analyses indicated that 17R-RvD1 enhanced expression of genes associated with cartilage matrix synthesis, and direct intraarticular treatment induced chondroprotection. Joint protective actions of 17R-RvD1 were abolished in RvD1 receptor-deficient mice termed ALX/fpr2/3(-/-) . These investigations open new therapeutic avenues for inflammatory joint diseases, providing mechanistic substance for the benefits of omega-3 supplementation in RA.
27974099 TNF inhibitors increase fat mass in inflammatory rheumatic disease: a systematic review wi 2017 Mar OBJECTIVES: To assess body composition of patients with inflammatory rheumatic disease and the effect of TNF inhibitors on it. METHODS: This was systematic review with meta-analysis of studies consulted on PubMed, Cochrane Library and EMBASE and assessing body composition in patients with rheumatoid arthritis or spondyloarthritis. We compared i) patients with healthy controls and ii) body components before and after TNF inhibitors. RESULTS: Among the 703 articles reviewed, 19 met the inclusion criteria. In patients with rheumatoid arthritis, a significant increase in fat mass (+1.85 kg, p=0.02), adiposity (+3.53%, p<0.00001) and android mass (+1.7 kg, p<0.00001) and a significant decrease in lean mass (-3.03 kg, p=0.01), were observed. In patients with spondyloarthritis, a significant but modest increase in fat mass (+0.69 kg, p=0.03) and a significant decrease in lean mass (-3.74 kg, p=0.03) were observed. Nine studies assessed impact of TNF inhibitors on body composition, with an increase of fat mass in the short and long term in all studies. Data on lean mass were controversial. Two studies found an increase in visceral or android mass under TNF inhibitors. CONCLUSIONS: Patients with inflammatory rheumatic disease have a significant decrease in lean mass and increase in fat mass. The use of TNF inhibitors is associated with a further increase in fat mass including android fat, which could potentially have cardiovascular consequences.
27274716 Synovial fluid proteome in rheumatoid arthritis. 2016 BACKGROUND: Rheumatoid arthritis (RA) is a chronic autoinflammatory disorder that affects small joints. Despite intense efforts, there are currently no definitive markers for early diagnosis of RA and for monitoring the progression of this disease, though some of the markers like anti CCP antibodies and anti vimentin antibodies are promising. We sought to catalogue the proteins present in the synovial fluid of patients with RA. It was done with the aim of identifying newer biomarkers, if any, that might prove promising in future. METHODS: To enrich the low abundance proteins, we undertook two approaches-multiple affinity removal system (MARS14) to deplete some of the most abundant proteins and lectin affinity chromatography for enrichment of glycoproteins. The peptides were analyzed by LC-MS/MS on a high resolution Fourier transform mass spectrometer. RESULTS: This effort was the first total profiling of the synovial fluid proteome in RA that led to identification of 956 proteins. From the list, we identified a number of functionally significant proteins including vascular cell adhesion molecule-1, S100 proteins, AXL receptor protein tyrosine kinase, macrophage colony stimulating factor (M-CSF), programmed cell death ligand 2 (PDCD1LG2), TNF receptor 2, (TNFRSF1B) and many novel proteins including hyaluronan-binding protein 2, semaphorin 4A (SEMA4D) and osteoclast stimulating factor 1. Overall, our findings illustrate the complex and dynamic nature of RA in which multiple pathways seems to be participating actively. CONCLUSIONS: The use of high resolution mass spectrometry thus, enabled identification of proteins which might be critical to the progression of RA.
26810262 Structure-activity relationship study of a series of novel oxazolidinone derivatives as IL 2016 Feb 15 A series of oxazolidinone and indole derivatives were synthesized and evaluated as IL-6 signaling blockers by measuring the effects of these compounds on IL-6-induced luciferase expression in human hepatocarcinoma HepG2 cells transfected with p-STAT3-Luc. Among different compounds screened, compound 4d was emerged as the most potent IL-6 signaling blockers with IC50 value of 5.9 μM which was much better than (+)-Madindoline A (IC50=21 μM), a known inhibitor of IL-6.
26788062 Serum Markers in Rheumatoid Arthritis: A Longitudinal Study of Patients Undergoing Inflixi 2015 Objective. The aim of this study was to investigate the clinical effect and serum markers in a cohort of rheumatoid arthritis patients with moderate to high disease activity, participating in an open clinical phase IV study conducted in Norway between 2001 and 2003 receiving infliximab treatment. Method. A total of 39 patients were studied, with a mean age of 54 years and 12-year disease duration. The analyses were performed using serum from patients at four assessment time points: baseline and 3, 6, and 12 months after starting treatment with infliximab. A wide variety of clinical data was collected and disease activity of 28 joints and Simple Disease Activity Index were calculated. The joint erosion was determined by X-ray imaging and the Sharp/van der Heijde score was determined. Serum analysis included multiplex immunoassays for 12 cytokines, 5 matrix metalloproteases, and 2 VEGFs. Results. The majority of the RA patients in this study had initially moderate to high disease activity and the infliximab treatment reduced the disease activity significantly and also reduced any further joint destruction and improved disease status. Most of the serum levels of cytokines and metalloproteases remained unchanged during the course of the study, and we were unable to detect changes in TNF-α in serum. Serum levels of IL-6 and VEGF-A decreased significantly after initiation of infliximab treatment. Conclusion. The serum levels of IL-6 and VEGF-A may be promising disease markers as they vary with disease progression. The clinical significance of these findings is yet to be determined and has to be confirmed in future clinical trials before being applied in the clinics.
26620687 Epidemiology of rheumatic diseases in Iran from analysis of four COPCORD studies. 2016 Nov AIM: To calculate the epidemiology of Rheumatic Diseases in Iran. MATERIALS AND METHODS: The data of Tehran, Zahedan, Sanandaj (urban) and Tuyserkan (rural) stage Community Oriented Program for the Control of Rheumatic Diseases (COPCORD) studies were gathered. The data were adjusted to the population number of the studied areas to represent Iran. RESULTS: The population of Iran is 75 149 669 (71.5% urban areas, males 50.4%) and of the mentioned area were respectively 10 000 000, 580 071, 311 444 and 109 262. The interviewed subjects were 10 291, 1565, 2100 and 5830. Male/female ratio was 0.9/1, 0.8/1, 08/1 and 0.8/1. Musculoskeletal complaints during the past 7 days (people aged ≥ 15 years) were detected in 44.7% of subjects. They were: shoulder 15.6%, wrist 10.4%, hands and fingers 10.2%, hip 8.3%, knee 27.4%, ankle 12.3%, toes 6.2%, cervical spine 14.2% and dorsolumbar spine 23.7%. Osteoarthritis (OA) was detected in 16.9%: knee 15.5%, hands 2.9% and hip 0.32%. Low back pain was found in 15.7%, sciatica in 0.94%, and soft tissue rheumatism in 4.6% (shoulder tenosynovitis 2.5%, frozen shoulder 0.56%, tennis elbow 1.2%, golf elbow 0.48%, de Quervain tenosynovitis 0.24%, trigger finger 0.2%, carpal tunnel syndrome 1.3%). Rheumatoid arthritis was detected in 0.37%, seronegative spondyloarthropathy in 0.24%, ankylosing spondylitis in 0.12%, systemic lupus erythematosus in 0.06%, Behcet's disease in 0.08%, fibromyalgia in 0.79% and gout in 0.13%. CONCLUSION: Compared to other COPCORD reports (17 countries), Iran gets the following rank: musculoskeletal complaints second, low back pain fourth, osteoarthritis second, knee osteoarthritis third, soft tissue rheumatism sixth, rheumatoid arthritis tenth, seronegative spondyloarthropathies fifth, gout eleventh and fibromyalgia fifth.
27196075 Endoscopic endonasal approach to the craniocervical junction: the importance of anterior C 2016 Apr We report our experience with the endoscopic endonasal approaches (EEA) for different craniocervical junction (CCJ) disorders to analyse outcomes and demonstrate the importance and feasibility of anterior C1 arch preservation or its reconstruction. Between January 2009 and December 2013, 10 patients underwent an endoscopic endonasal approach for different CCJ pathologies at our Institution. In 8 patients we were able to preserve the anterior C1 arch, while in 2 post-traumatic cases we reconstructed it. The CCJ disorders included 4 cases of irreducible anterior bulbo-medullary compression secondary to rheumatoid arthritis or CCJ anomalies, 4 cases of inveterate fractures of C1 and/or C2 and 2 tumours. Pre- and postoperative neuroradiological evaluation was always obtained by magnetic resonance imaging (MRI), computed tomographic (CT) scanning and dynamic cranio-vertebral junction x-ray. Pre- and postoperative neurologic disability assessment was obtained by Ranawat classification for patients with rheumatoid arthritis and by Nurick classification for the others. At a mean follow-up of 31 months (range: 14-73 months), an improvement of at least one Ranawat or Nurick classification level was observed in 6 patients, while in another 4 patients neurological conditions were stable. Radiological follow-up revealed an adequate bulbo-medullary decompression in all patients and a regular bone fusion in cases of C1 and/or C2 fractures. In all patients spinal stability was preserved and none required subsequent posterior fixation. The endoscopic endonasal surgery provided adequate exposure and a low morbidity minimally invasive approach to the antero-medial located lesions of the CCJ, resulting in a safe, effective and well-tolerated procedure. This approach allowed preservation of the anterior C1 arch and the avoidance of a posterior fixation in all patients of this series, thus preserving the rotational movement at C0-C2 segment and reducing the risk of a subaxial instability development.
26984804 Racial/Ethnic Disparity in Rates and Outcomes of Total Joint Arthroplasty. 2016 Apr Racial/ethnic disparity in total joint arthroplasty (TJA) has grown over the last two decades as studies have documented the widening gap between Blacks and Whites in TJA utilization rates despite the known benefits of TJA. Factors contributing to this disparity have been explored and include demographics, socioeconomic status, patient knowledge, patient preference, willingness to undergo TJA, patient expectation of post-arthroplasty outcome, religion/spirituality, and physician-patient interaction. Improvement in patient knowledge by effective physician-patient communication and other methods can possibly influence patient's perception of the procedure. Such interventions can provide patient-relevant data on benefits/risks and dispel myths related to benefits/risks of arthroplasty and possibly reduce this disparity. This review will summarize the literature on racial/ethnic disparity on TJA utilization and outcomes and the factors underlying this disparity.
26442128 Physical activity of elderly patients with rheumatoid arthritis and healthy individuals: a 2015 BACKGROUND: Most people with rheumatoid arthritis (RA) are physically inactive. An accelerometer worn on the waist has been used to evaluate physical activity in people with chronic conditions. It is useful for evaluating moderate to vigorous activity, although it tends to underestimate light or mild activities such as housework or family duties. An accelerometer worn on the wrist (i.e., actigraph) has recently been used to capture daily physical activity in inactive individuals. The purposes of this study were to investigate physical activity measured by an actigraph in patients with RA and in healthy individuals and to investigate the association between actigraphic data and self-reported physical function. METHODS: The subjects were 20 RA patients and 20 healthy individuals. All participants wore an actigraph on their wrist for 6-7 consecutive days. They also completed the Health Assessment Questionnaire disability index (HAQ-DI) and the Medical Outcomes Study (MOS) 36-item short form health survey (SF-36). We extracted three parameters from the actigraphic data: mean activity count (MAC), peak activity count (PAC), and low activity ratio (LAR). These three parameters were compared between the RA patients and healthy individuals and with the self-reported questionnaires. RESULTS: The MAC was significantly lower and the LAR was significantly higher in RA patients than in healthy individuals. The PAC was not different between the two groups. The LAR was negatively correlated with the MAC for the RA patients and for the healthy individuals. The decrease ratio of the LAR with the increase of the MAC for the RA patients was twice that of the healthy participants. In the RA patients, the LAR was significantly and moderately correlated with the HAQ-DI score and two dimensions of the SF-36 (i.e., "physical functioning" and "bodily pain"). CONCLUSION: Investigation of the proportion of low activity count using an actigraph may be useful to identify characteristics of the physical function in RA patients.
25580811 Design, synthesis, X-ray crystallographic analysis, and biological evaluation of thiazole 2015 Feb 12 Human dihydroorotate dehydrogenase (HsDHODH) is a flavin-dependent mitochondrial enzyme that has been certified as a potential therapeutic target for the treatment of rheumatoid arthritis and other autoimmune diseases. On the basis of lead compound 4, which was previously identified as potential HsDHODH inhibitor, a novel series of thiazole derivatives were designed and synthesized. The X-ray complex structures of the promising analogues 12 and 33 confirmed that these inhibitors bind at the putative ubiquinone binding tunnel and guided us to explore more potent inhibitors, such as compounds 44, 46, and 47 which showed double digit nanomolar activities of 26, 18, and 29 nM, respectively. Moreover, 44 presented considerable anti-inflammation effect in vivo and significantly alleviated foot swelling in a dose-dependent manner, which disclosed that thiazole-scaffold analogues can be developed into the drug candidates for the treatment of rheumatoid arthritis by suppressing the bioactivity of HsDHODH.
26581485 Adult onset Still's disease associated with malignancy-Cause or coincidence? 2016 Apr OBJECTIVE: To analyze all patients with adult onset Still's disease (AOSD) and malignancy described in the literature and to discuss their relation to each other. METHOD: Demographic, clinical, and laboratory characteristics of one index patient with AOSD seen in our institution who subsequently developed a malignant disease were compared with all other cases of AOSD and malignancy identified by a PubMed literature research. Furthermore, characteristics of AOSD patients with malignancy were compared to those without malignancy. RESULTS: We found 46 articles in English, French, Japanese, Korean, and Spanish language reporting 47 cases in addition to our own case. In 36 patients, the diagnosis of AOSD could be confirmed by retrospectively applying classification criteria according to Yamaguchi, Fautrel, and Crispin. The median time between diagnosis of AOSD and subsequent detection of a malignant disease was 9 months, 50% had a hematological disorder and 50% a solid tumor. In 33%, the symptoms of AOSD resolved after successful therapy of the neoplastic disease. Red flags for paraneoplastic AOSD were onset of symptoms at higher age, atypical features of rash, highly elevated lactate dehydrogenase, atypical cells in the differential blood count, and high concentrations of the soluble interleukin-2 receptor. CONCLUSION: A disease resembling AOSD can precede the clinical appearance of a hematologic malignancy or a solid tumor. Thorough diagnostic work-up of AOSD to rule out malignancy and awareness to conspicuous signs for malignancy-associated AOSD are therefore essential in the clinical work-up of such patients.
25964045 Anti-inflammatory activity of green versus black tea aqueous extract in a rat model of hum 2017 Feb AIM: Recently, there has been an increasing interest in tea (Camellia sinensis) as a protective agent against inflammatory diseases. Here, we evaluated/compared the anti-inflammatory activity of two different doses (0.5 and 1.0 g/kg body weight) of green tea aqueous extract (GTE, rich in catechins) and black tea aqueous extract (BTE, rich in theaflavins and thearubigins) in rat adjuvant-induced arthritis (AIA). METHODS: Adjuvant-induced arthritis rat model received orally/daily distilled water as vehicle, indomethacin (1.0 mg/kg body weight; a non-steroidal/anti-inflammatory drug), or tea aqueous extracts (for 28 or 14 consecutive days starting from day 0 or 14 of arthritis induction, respectively). RESULTS: The present study showed that only the high dose of GTE (from day 0) significantly alleviated (P < 0.05-0.001) all complications shown in arthritic rats, including synovial joint inflammation, elevation in erythrocyte sedimentation rate, blood leukocytosis (due to lymphocytosis and neutrocytosis), and changes in weight/cellularity of lymphoid organs. The anti-arthritic activity of the high dose of GTE (from day 0) was comparable (P > 0.05) with that of indomethacin (12.9-53.8 vs. 9.5-48.4%, respectively) and mediated by significantly decreasing and down-regulating (P < 0.001) the systemic production of pro-inflammatory cytokines and the expression of chemokine receptor-5 in synovial tissues, respectively. Moreover, the anti-arthritic activity of tea aqueous extracts was in the following order: high dose of GTE > low dose of GTE ≥ high dose of BTE > low dose of BTE. CONCLUSION: The present study proved the anti-inflammatory activity of GTE over BTE and equal to that of indomethacin in AIA rat model.
26236341 Current Concepts in the Management of Rheumatoid Hand. 2015 Rheumatoid arthritis (RA) is a chronic inflammatory disease caused by a T cell-driven autoimmune process, which majorly involves the diarthrodial joints. It affects 1% of the US population, and approximately 70% of patients with RA develop pathologies of the hand, especially of the metacarpophalangeal joints (MCP). Furthermore, also the extensor and flexor tendons of the fingers are frequently involved. The first line of treatment should be conservative. Three general classes of drugs are currently available for RA: nonsteroidal anti-inflammatory agents (NSAIDs), corticosteroids, and disease modifying antirheumatic drugs (DMARDs). Encouraging results have been obtained using DMARDs. However, when severe deformities occur or when patients are unresponsive to medical management and injections therapy, surgical intervention should be performed to relieve pain and restore function. Several surgical options have been described for the management of MCP joint deformities, including soft tissue procedures, arthrodesis, and prosthetic replacement. Tendons ruptures are generally managed with tendon transfer surgery, while different surgical procedures are available to treat fingers deformities. The aim of the present review is to report the current knowledge in the management of MCP joint deformities, as well as tendons damage and fingers deformities, in patients with RA.
27981462 An educational leaflet improves response to invitation for screening for arthritis in pati 2017 Mar This study hypothesises that an educational leaflet about psoriatic arthritis (PsA) will improve psoriasis patients' attendance for screening for PsA. A random sample of patients ≥18 years old with a coded diagnosis of psoriasis and no diagnosis of PsA, rheumatoid arthritis or ankylosing spondylitis were identified from five GP surgeries in Yorkshire, UK. Patients were randomised 1:1 to receive study information alone or with the educational leaflet, with an invitation to attend for a screening examination by a dermatologist and rheumatologist. Nine hundred thirty-two invitation packs were sent to recruit 191 (20.5%) participants. One hundred sixty-nine (88.5%) had current or previous psoriasis and 17 (10.1%) had previously undiagnosed PsA. The estimated prevalence of PsA was 18.1% (95% CI: 16.2, 20.1%).The response rate was lower than expected and was not significantly higher when patients received the educational leaflet (22.8 vs 18.3%, p = 0.08). Response rates varied by practice (14.7 to 30.6%). However, deprivation scores for each practice revealed a significant increase in response with the leaflet for deprivation decile of 3 (p < 0.001) but no significant differences in the other practices. An educational leaflet about PsA improves attendance for screening in primary care, but only in those practices with higher levels of socioeconomic deprivation.
26286188 The Evaluation of the Therapeutic Efficacy and Side Effects of a Macromolecular Dexamethas 2016 Jan PURPOSE: To investigate the efficacy and safety of N-(2-hydroxypropyl) methacrylamide (HPMA) copolymer-dexamethasone conjugate (P-Dex) in the collagen-induced arthritis (CIA) mouse model. METHODS: HPMA copolymer labeled with a near infrared fluorescence (NIRF) dye was administered to mice with CIA to validate its passive targeting to inflamed joints and utility as a drug carrier system. The CIA mice were treated with P-Dex, dexamethasone (Dex) or saline and the therapeutic efficacy and skeletal toxicity evaluated using clinical scoring and micro-computed tomography (μ-CT). RESULTS: The NIRF signal of the HPMA copolymer localized to arthritic joints consistent with its passive targeting to sites of inflammation. While the CIA mice responded more rapidly to P-Dex compared to Dex, the final clinical score and endpoint μ-CT analyses of localized bone erosions indicated that both single dose P-Dex and dose equivalent daily Dex led to comparable clinical efficacy after 30 days. μ-CT analysis of the proximal tibial metaphyses showed that P-Dex treatment was associated with significantly higher BMD and BV/TV compared to Dex and the saline control, consistent with reduced glucocorticoid (GC) skeletal toxicity. CONCLUSION: These results validate the therapeutic efficacy of P-Dex in the CIA mouse model. P-Dex treatment averted the adverse effects of GC's on systemic bone loss, supporting its utility in clinical development for the management of rheumatoid arthritis.
26850811 Mind body therapies in rehabilitation of patients with rheumatic diseases. 2016 Feb Mind body therapies (MBT) share a global approach involving both mental and physical dimensions, and focus on relationship between brain, mind, body and behavior and their effects on health and disease. MBT include concentration based therapies and movement based therapies, comprising traditional Oriental practices and somatic techniques. The greatest part of rheumatic diseases have a chronic course, leading to progressive damages at musculoskeletal system and causing physical problems, psychological and social concerns. Thus, rheumatic patients need to be treated with a multidisciplinary approach integrating pharmacological therapies and rehabilitation techniques, that not should only aim to reduce the progression of damages at musculoskeletal system. Thus, MBT, using an overall approach, could be useful in taking care of the overall health of the patients with chronic rheumatic diseases. This review will deal with different MBT and with their effects in the most common chronic rheumatic diseases (Rheumatoid Arthritis, Ankylosing Spondylitis, Fibromyalgia Syndrome).
26785775 Effect of M3 muscarinic acetylcholine receptor deficiency on collagen antibody-induced art 2016 Jan 19 BACKGROUND: There is increasing evidence that the non-neuronal cholinergic system might be of importance for the pathology of rheumatoid arthritis. The role of M3 muscarinic acetylcholine receptor (M3R) in this regard has, however, not been investigated to date. Thus, in the present study we analyzed if M3R deficiency might have a protective effect on experimentally induced arthritis. METHODS: Collagen antibody-induced arthritis (CAIA) was evoked in M3R-deficient (M3R(-/-)) mice and wild-type (WT) littermates. Severity of arthritis was assessed by scoring of paw swelling. The joints of arthritic and nonarthritic animals were analyzed for histopathological changes regarding synovial tissue, cartilage degradation and bone destruction. Further, gene expression analysis of respective markers was performed. Systemic and local inflammatory response was determined by flow cytometry and immunohistochemistry for leukocytes as well as mRNA and protein measurements for pro-inflammatory cytokines and chemokines. RESULTS: In arthritic M3R(-/-) mice the number of leukocytes, specifically neutrophils, was enhanced even though clinical arthritis score was not significantly different between WT and M3R(-/-) mice with CAIA. In M3R(-/-) mice, levels of neutrophil chemoattractant chemokine C-X-C-motif ligand 2 (CXCL2) as well as the pro-inflammatory cytokine interleukin-6 were already strongly increased in mice with low arthritis score, whereas WT mice only showed prominent expression of these markers when reaching high arthritis scores. Furthermore, arthritic M3R(-/-) mice displayed a stronger degradation of collagen II in the articular cartilage and, most strikingly, histopathological evaluation revealed more severe bone destruction in arthritic mice with M3R deficiency compared to WT littermates. Moreover, in M3R(-/-) mice, gene expression of markers for bone degradation (matrix metalloproteinase 13, cathepsin K and receptor activator of nuclear factor-κB ligand) was already increased in mice with low arthritis score. CONCLUSIONS: Taken together, the present study shows that while M3R(-/-) mice were not protected from CAIA, they had a tendency toward a higher inflammatory response after arthritis induction than WT mice. Further, arthritis-induced joint destruction was significantly stronger in mice with M3R deficiency, indicating that stimulation of M3R might have protective effects on arthritis.
25974389 Association between cannabinoid receptor type 2 Q63R variant and oligo/polyarticular juven 2015 OBJECTIVES: To investigate whether the functional variant Q63R of the cannabinoid 2 (CB2) receptor is associated with susceptibility to oligo/poly-articular juvenile idiopathic arthritis (JIA) and with its clinical features. METHOD: A total of 171 Italian children with oligoarticular/rheumatoid factor negative poly-articular JIA and 600 healthy controls were enrolled in the study and genotyped. RESULTS: A significant difference in genotype distribution of the CB2 Q63R variant (CNR2 rs35761398) between oligo/poly-articular JIA patients and controls was found (p = 0.001). The R63 variant was associated with increased rates of relapse (p = 0.0001). CONCLUSIONS: This study indicates that the CB2 receptor contributes to susceptibility to oligo/polyarticular JIA and to the severity of its clinical course.
26343051 Cannabinoid-based drugs targeting CB1 and TRPV1, the sympathetic nervous system, and arthr 2015 Sep 6 Chronic inflammation in rheumatoid arthritis (RA) is accompanied by activation of the sympathetic nervous system, which can support the immune system to perpetuate inflammation. Several animal models of arthritis already demonstrated a profound influence of adrenergic signaling on the course of RA. Peripheral norepinephrine release from sympathetic terminals is controlled by cannabinoid receptor type 1 (CB1), which is activated by two major endocannabinoids (ECs), arachidonylethanolamine (anandamide) and 2-arachidonylglycerol. These ECs also modulate function of transient receptor potential channels (TRPs) located on sensory nerve fibers, which are abundant in arthritic synovial tissue. TRPs not only induce the sensation of pain but also support inflammation via secretion of pro-inflammatory neuropeptides. In addition, many cell types in synovial tissue express CB1 and TRPs. In this review, we focus on CB1 and transient receptor potential vanilloid 1 (TRPV1)-mediated effects on RA since most anti-inflammatory mechanisms induced by cannabinoids are attributed to cannabinoid receptor type 2 (CB2) activation. We demonstrate how CB1 agonism or antagonism can modulate arthritic disease. The concept of functional antagonism with continuous CB1 activation is discussed. Since fatty acid amide hydrolase (FAAH) is a major EC-degrading enzyme, the therapeutic possibility of FAAH inhibition is studied. Finally, the therapeutic potential of ECs is examined since they interact with cannabinoid receptors and TRPs but do not produce central side effects.