Site: About Arthritis

Arthrography - What You Need to Know
Has your doctor discussed arthrography with you as part of determining why you may be having joint pain or joint stiffness, among other arthritis symptoms? Arthrography is an imaging technique...

Arthritis Vaccine - A Reality Sooner Rather Than Later?
Any time there's breaking news having to do with rheumatoid arthritis, and the words "cure" or "vaccine" are involved, you've grasped my attention and the attention of countless other rheumatoid...

Foot Orthotics May Relieve Arthritis Pain
If you have arthritis in your feet, your doctor may recommend foot orthotics to help relieve pain and provide support while improving how you walk. Foot orthotics are shoe inserts...

TNF Blockers - Does Their Use Predict Work Disability?
TNF blockers are an important treatment option for rheumatoid arthritis patients. Enbrel, the first TNF blocker that was marketed in 1998, arrived on the scene with great promise -- the...

B-cells Can Act Independently in Rheumatoid Arthritis, Lupus
In systemic autoimmune diseases, such as rheumatoid arthritis and lupus, B-cells can be activated in the absence of T-cells, according to Yale University researchers. The new findings oppose a long-held...

Recovering from Stroke More Difficult for Rheumatoid Arthritis Patients
People with rheumatoid arthritis who have had a stroke have lower functional ability than stroke patients who don't have arthritis. According to researchers from University Texas Medical Branch, a study...

Interleukin 10 (IL-10) Suppresses Immune System, According to Researchers
A cytokine, called interleukin 10 (IL-10) is secreted to suppress the immune system in response to the inflammation produced by autoimmune diseases. This finding could be important in terms of...

Joint Registry Needed to Track Problem Hip and Knee Replacements
Joint replacements can fail for various reasons, one of which is a defective prosthesis. When this happens, patients may need a replacement of their replacement -- and certainly it would...

Actemra (tocilizumab) Recommended for Approval by FDA Advisory Committee
Actemra (tocilizumab), the first interleukin-6 receptor-inhibiting monoclonal antibody for the treatment of rheumatoid arthritis, has been recommended for approval by the FDA Arthritis Advisory Committee. The vote to approve was...

Chronic Pain Remains a Burden for Arthritis Patients
Chronic pain is characteristic of many diseases, including arthritis. Reportedly, 75 million Americans live with some type of chronic or recurrent pain. The Centers for Disease Control and Prevention has...

Site: MedicineNet Arthritis General

Strep Throat
Title: Strep Throat
Category: Diseases and Conditions
Created: 12/31/1997
Last Editorial Review: 8/19/2008

Gout
Title: Gout
Category: Diseases and Conditions
Created: 12/31/1997
Last Editorial Review: 8/18/2008

Knee Pain
Title: Knee Pain
Category: Diseases and Conditions
Created: 12/31/1997
Last Editorial Review: 8/18/2008

Snoring
Title: Snoring
Category: Diseases and Conditions
Created: 11/29/2005
Last Editorial Review: 8/18/2008

Lack of Energy in Old Age May Foretell Illness
Title: Lack of Energy in Old Age May Foretell Illness
Category: Health News
Created: 8/15/2008 2:00:00 AM
Last Editorial Review: 8/15/2008

Cheerleading Leads the Pack in Injuries
Title: Cheerleading Leads the Pack in Injuries
Category: Health News
Created: 8/15/2008
Last Editorial Review: 8/15/2008

Postmenopausal Women With Breast Cancer Face Joint Issues
Title: Postmenopausal Women With Breast Cancer Face Joint Issues
Category: Health News
Created: 8/13/2008 9:18:00 AM
Last Editorial Review: 8/13/2008

Powerful Antacid Drugs Raise Fracture Risk
Title: Powerful Antacid Drugs Raise Fracture Risk
Category: Health News
Created: 8/12/2008 2:00:00 AM
Last Editorial Review: 8/12/2008

Obese and Healthy?
Title: Obese and Healthy?
Category: Health News
Created: 8/12/2008
Last Editorial Review: 8/12/2008

Scoliosis
Title: Scoliosis
Category: Diseases and Conditions
Created: 8/30/1999 7:19:00 PM
Last Editorial Review: 8/11/2008

B Cells Can Act Alone in Autoimmune Diseases
Title: B Cells Can Act Alone in Autoimmune Diseases
Category: Health News
Created: 8/8/2008 2:00:00 AM
Last Editorial Review: 8/8/2008

Survey Shows Under 2% Have Epilepsy
Title: Survey Shows Under 2% Have Epilepsy
Category: Health News
Created: 8/8/2008
Last Editorial Review: 8/8/2008

Site: Arthritis Research & Therapy - Latest articles

Circulating immune complexes contain citrullinated fibrinogen in rheumatoid arthritis
IntroductionThere is increasing evidence that autoantibodies and immune complexes (ICs) contribute to synovitis in rheumatoid arthritis (RA), yet the autoantigens incorporated in ICs in RA remain incompletely characterized. Methods: We utilized C1q to capture ICs from plasma derived from human RA and control patients, followed by detection with antibodies specific for: (i) immunoglobulin to detect ICs, and (ii) fibrinogen to detect fibrinogen-containing ICs. RA and control plasma were separated by liquid chromatography, and fractions characterized by ELISA, immunoblotting and mass spectrometry. Immunohistochemical staining was performed on rheumatoid synovial tissue. Results: C1q-immunoassays demonstrated increased levels of IgG (P = 0.01) and IgM (P = 0.0002) ICs in plasma derived from RA patients possessing anti-cyclic citrullinated peptide autoantibodies (CCP+) as compared to healthy controls. About one-half of the CCP+ RA possessed circulating ICs containing fibrinogen (P = 0.0004). Fractionation of whole RA plasma revealed citrullinated fibrinogen in the high molecular weight fractions that contained immune complexes. Positive correlations were observed between fibrinogen containing immune complex and anti-citrullinated fibrinogen autoantibodies, anti-CCP antibody, rheumatoid factor and certain clinical characteristics. Immunohistochemical staining demonstrated co-localization of fibrinogen, immunoglobulin and complement component C3 in RA pannus tissue. Mass spectrometry analysis of immune complexes immunoprecipitated from RA pannus tissue lysates demonstrated the presence of citrullinated fibrinogen. Conclusions: Circulating ICs containing citrullinated fibrinogen are present in one-half of CCP+ RA patients, and these immune complexes co-localize with C3 in the rheumatoid synovium suggesting that they contribute to synovitis in a subset of RA patients.

TH-17 cells in rheumatoid arthritis
IntroductionThis study was conducted to quantify the number of TH-17 cells present in rheumatoid arthritis (RA) synovial fluid (SF) and the to determine the level of IL-17 cytokine in RA, osteoarthritis (OA) and normal synovial tissue, as well as to examine SF macrophages for the presence of IL-23, IL-27 and interferon (IFN)-g. Methods: Peripheral blood (PB) mononuclear cells from normal and RA donors and mononuclear cells from RA SF were examined either without stimulation, or after pretreatment with IL-23 followed by stimulation with PMA plus ionomycin (P/I). The abundance of TH-17 cells in RA SF was determined by flow cytometry. IL-17 levels were quantified in synovial tissue from RA, OA and normal individuals by ELISA. IL-23 was identified in SFs by ELISA. RA SF and control in vitro differentiated macrophages were either untreated or treated with the Toll like receptor (TLR)2 ligand peptidoglycan, and then IL-23, IL-27 and IFN-g mRNA levels were quantified by real-time RT-PCR. Results: Treatment with P/I alone or combined with IL-23 significantly increased the number of TH-17 cells in normal and RA PB and in RA SF. With or without P/I plus IL-23, the percentage of TH-17 cells was higher in RA SF compared to normal and RA PB. IL-17 levels were comparable in OA and normal synovial tissues, and these values were significantly increased in RA synovial tissue. Although IL-17 was readily detected in RA SFs, IL-23 was rarely identified in RA SF. However, IL-23 mRNA was significantly increased in RA SF macrophages compared to control macrophages, with or without TLR2 ligation. IL-27 mRNA was also significantly higher in RA SF compared to control macrophages, but there was no difference in IL-27 levels between RA and control macrophages following TLR2 ligation. IFN-g mRNA was also detectable in RA SF macrophages but not control macrophages and the increase of IFN-g mRNA following TLR2 ligation was greater in RA SF macrophages compared to control macrophages. Conclusions: These observations support a role for TH-17 cells in RA. Our observations do not strongly support a role or IL-23 in the generation to TH-17 cells in the RA joint, however, they suggest that strategies which enhance IL-27 or IFN-g might modulate the presence of TH-17 cells in RA.

Cia5d regulates a new fibroblast-like synoviocyte invasion-associated gene expression signature
IntroductionThe in vitro invasive properties of rheumatoid arthritis (RA) fibroblast-like synoviocytes (FLS) have been shown to correlate with disease severity and radiographic damage. We have recently determined that FLS obtained from pristane-induced arthritis (PIA)-susceptible DA rats are also highly invasive in the same in vitro assay through Matrigel. The transfer of alleles derived from the arthritis-resistant F344 strain at the arthritis severity locus Cia5d (RNO10), as in DA.F344(Cia5d) congenics, was enough to significantly and specifically reduce the invasive properties FLS. This genetically controlled difference in FLS invasion involves increased production of soluble membrane-type 1 matrix metalloproteinase (MT1-MMP) by DA, and is dependent on increased activation of matrix metalloproteinase-2 (MMP-2). In the present study we aimed at characterizing the pattern of gene expression that correlates with differences in invasion in order to identify pathways regulated by the Cia5d locus. Methods: Synovial tissues were collected from DA and DA.F344(Cia5d) rats 21 days after the induction of PIA. Tissues were digested and FLS isolated. After a minimum of four passages FLS were plated on Matrigel-covered dishes at similar densities for 24h, followed by RNA extraction. Illumina RatRef-12 expression BeadChip arrays were used. Expression data were normalized, followed by t-test, logistic regression and cluster analysis. Real-time quantitative polymerase chain reaction (QPCR) was used for validation of the microarray data. Results: 7,665 genes out of the 22,523 RefSeq gene probes present in the array were expressed by the FLS. The expression of 66 genes was significantly different between the DA and DA.F344(Cia5d) FLS (P<0.01). Nineteen of the 66 differentially expressed genes (28.7%) are genes involved in the regulation of cell cycle progression or cancer-associated phenotypes such as invasion and contact inhibition. These included Cxcl10, Vil2 and Nras, three genes up-regulated in DA and known to regulate MMP-2 expression and activation. Nine of the 66 genes (13.6%) are involved in the regulation of the estrogen receptor signaling or transcription. Five candidate genes located within the Cia5d interval were also differentially expressed. Conclusions: We have identified a novel FLS invasion-associated gene expression signature regulated by Cia5d. Many of the genes differentially expressed have been previously implicated in cancer cell phenotypes, including invasion, suggesting a parallel in the behavior of arthritis FLS and cancer cells, and raising novel pathways and genes for therapeutic intervention and prognostication.

Interferon-induced protein IFIT4 is associated with systemic lupus erythematosus and promotes differentiation of monocytes into DC-like cells
IntroductionA multitude of interferon (IFN)-inducible genes (IFIGs) was found highly expressed in the peripheral blood mononuclear cells (PBMC) of most patients with systemic lupus erythematosus (SLE) via oligonucleotide microarray. Among these IFIGs, interferon-induced protein with tetratricopeptide repeats 4 (IFIT4) is a novel gene with function unknown. Methods: In this study, we studied the role of IFIT4 in monocyte differentiation and the correlation between IFIT4 expression and the clinical manifestation of SLE using plasmid transfection, flow cytometry, mixed leukocyte responses (MLRs), ELISA, quantitative RT-PCR and Western blotting. Results: We found that both IFIT4 mRNA and protein expression levels were significantly higher in PBMCs and monocytes from SLE patients than those from healthy controls. IFIT4 expression was positively correlated with ANA, anti-dsDNA, and anti-Sm auto-immune antibodies in SLE. SLE patients with higher expression of IFIT4 had a higher prevalence of leucopenia, thrombocytopenia, and C3/C4 decrease. IFIT4 protein was localized exclusively in the cytoplasm, and significantly up-regulated by IFN-alpha in normal PBMCs. To determine the role of IFIT4 in monocyte differentiation, the monocytic cell line THP-1 was transfected with pEGFP-IFIT4 expression plasmid and stimulated with GM-CSF/IL-4 to generate IFIT4-primed DC-like cells (DCLCs). IFIT4-primed DCLCs acquired morphological characteristics of DCs more quickly with a greater resemblance to DCs and had higher expression of CD40, CD86, CD80, HLA-DR, and CD83, along with lower expression of CD14; increased IL-12 secretion; and an increased ability to stimulate T cell proliferation than DCLCs primed with a pEGFP-C1 control plasmid trasfection. Besides, IFIT4-primed DCLCs enhanced the IFN-gamma secretion (about 2.4 fold) by T cells compared with controls. Conclusions: Our findings suggested that IFIT4 might play a role in promoting monocyte differentiation into DCLCs and directing DCLCs to modulate Th1 cells differentiation, all of which might contribute to the autoimmunity and pathogenesis of SLE.

The role of fibroblast growth factor-8 (FGF8) in animal models of osteoarthritis
IntroductionFibroblast growth factor-8 (FGF8) is isolated as an androgen-induced growth factor and recently has shown to contribute to limb morphogenesis. The aim of this study was to clarify the role of FGF8 in animal models of osteoarthritis (OA). Methods: The expression of FGF8 in the partial meniscectomy model of OA in the rabbit knee was examined by immunohistochemistry. The effect of intraperitoneal administration of anti-FGF8 antibody was tested in a model of OA that employed injection of monoiodoacetic acid (MIA) or FGF8 into the knee joint of rats. Effect of FGF8 was also tested using cultured chondrocytes. Rabbit articular chondrocytes were treated with FGF8 for 48 hours, and the production of matrix metalloproteinase and the degradation of sulfated glycosaminoglycan in the extracellular matrix (ECM) were measured. Results: The expression of FGF8 in hyperplastic synovial cells and fibroblasts was induced in the meniscectomized OA model, whereas little or no expression was detected in normal synovium. Injection of FGF8 into rat knee joints induced the degradation of ECM, which was suppressed by anti-FGF8 antibody. In the MIA-induced arthritis model, anti-FGF8 antibody reduced ECM release into the synovial cavity. In cultured chondrocytes, FGF8 induced the release of matrix metalloproteinase 3 and prostaglandin E2 and caused degradation of ECM. The combination of FGF8 and interleukin-1alpha accelerated the degradation of ECM. Anti-FGF8 antibody suppressed the effects of FGF8 on the cells. Conclusions: FGF8 is produced by injured synovium and it enhances the production of protease and PGE2 from inflamed synoviocytes. Degradation of ECM is enhanced by FGF8. Therefore, FGF8 may participate in the degradation of cartilage and exacerbation of osteoarthritis.

Suppression of bone morphogenetic protein inhibitors promotes osteogenic differentiation: therapeutic implications
Bone morphogenetic proteins (BMPs) are expressed during osteogenesis and their action is regulated by corresponding BMP inhibitors. Chordin (a well recognized BMP inhibitor) and BMP-2 are expressed during osteogenic differentiation of human mesenchymal stem cells. Chordin inhibition induces human mesenchymal stem cell differentiation and reduces their proliferation by increasing BMP-2 bioavailability. The potential of suppressing BMP inhibitors is emerging as a biological therapeutic target in bone tissue engineering, because it results in an unopposed synergy between the various growth factors that are involved in osteogenesis, within their physiological milieu.

Adipose-derived mesenchymal stem cells from the sand rat: TGFbeta and 3D coculture with human disc cells stimulate proteoglycan and collagen type I rich extracellular matrix
IntroductionAdult mesenchymal stem cell therapy has potential application in the biologic treatment of disc degeneration. Our objectives were: 1) To direct adipose-derived mesenchymal stem cells (AD-MSC) from the sand rat to produce a proteoglycan and collagen type I extracellular matrix (ECM) rich in known ECM components of the annulus fibrosis of disc and 2) To stimulate proteoglycan production by co-culture of human annulus cells with AD-MSC. Methods: AD-MSC were isolated and characterized by adherence to plastic, appropriate expression of CD markers, and differentiation to osteoblasts and chondrocytes in vitro. AD-MSC were grown in three dimensional (3D) culture and treated with or without transforming growth factor beta (TGFbeta) to direct them to produce annulus-like ECM as determined by proteoglycan content and collagen expression. AD-MSC were cocultured with human annulus cells and grown in 3D culture. Results: AD-MSC produced a proteoglycan and collagen type I rich matrix following treatment with TGFbeta in 3D culture as confirmed by a 48% increase in proteoglycan content as assayed by 1,9-dimethylmethylene blue (DMB), and by immunohistochemical identification of extracellular matrix components. Coculture of human annulus and sand rat AD-MSC in 3D resulted in a 20% increase in proteoglycan production compared to the predicted value of the sum of the individual cultures. Conclusions: Results support the hypothesis that AD-MSC have potential in cell-based therapy for disc degeneration.

Association of the FCRL3 gene with rheumatoid arthritis: a further example of population specificity?
No abstract available

Biology and therapy of fibromyalgia. Evidence-based biomarkers for fibromyalgia syndrome
Researchers studying fibromyalgia strive to identify objective, measurable biomarkers that may identify susceptible individuals, may facilitate diagnosis, or that parallel activity of the disease. Candidate objective measures range from sophisticated functional neuroimaging to office-ready measures of the pressure pain threshold. A systematic literature review was completed to assess highly investigated, objective measures used in fibromyalgia studies. To date, only experimental pain testing has been shown to coincide with improvements in clinical status in a longitudinal study. Concerted efforts to systematically evaluate additional objective measures in research trials will be vital for ongoing progress in outcome research and translation into clinical practice.

Increased susceptibility to collagen-induced arthritis in female mice carrying congenic Cia40/Pregq2 fragments
IntroductionCollagen-induced arthritis (CIA) in mice is a commonly used experimental model for rheumatoid arthritis (RA). We have previously identified a significant quantitative trait locus denoted Cia40 on chromosome 11 that affects CIA in older female mice. This locus co-localizes with another locus, denoted Pregq2, known to affect reproductive success. The present study was performed to evaluate the role of the Cia40 locus in congenic B10.Q mice, and identify possible polymorphic candidate genes, which may also be relevant in the context of RA. Methods: Congenic B10.Q mice carrying a NFR/N fragment surrounding the Cia40/Pregq2 loci were created by 10 generations of backcrossing (N10). The congenic mice were investigated in the CIA model, and the incidence and severity of arthritis were recorded as well as the serum levels of anti-collagen II (CII) antibodies. Results: Significant effects on onset, incidence, severity and anti-CII antibody titres were observed in female mice carrying a heterozygous congenic Cia40/Pregq2 fragment of NFR/N origin, containing one or more polymorphic genes. Congenic male mice did not show increased incidence of CIA, but males carrying a heterozygous fragment showed a significant increase in severity in comparison to wildtype B10.Q males (littermates). Conclusions: The Cia40/Pregq2 locus at chromosome 11 contains one or more polymorphic genes of NFR/N origin that significantly influence both incidence and severity of CIA in heterozygous congenic mice of the B10.Q strain. The major polymorphic candidate genes for the effects on CIA are Cd79b, Abca8a and Map2k6. The congenic fragment also contains polymorphic genes that affect reproductive behavior and reproductive success. The Sox9 gene, known to influence sex reversal, is a candidate gene for the reproductive phenotype.