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Roche Suspends Phase III Trials for Ocrelizumab
 Roche, a Swiss pharmaceutical company, has suspended late-stage clinical trials of a biologic drug being developed to treat rheumatoid arthritis and lupus. The drug, ocrelizumab, is a fully human monoclonal antibody against CD-20 positive lymphocytes. In plain English, it was being developed as an anti-B cell therapy similar to Rituxan (rituximab).
Johns Hopkins reported that ocrelizumab was expected to "reduce the development of drug neutralizing antibodies and infusion reactions" compared to rituximab. In theory, sounds like progress. Instead, it has been established that the safety risk associated with ocrelizumab outweighed the benefits. Roche has disclosed that several patients died from infections -- the exact number has not yet been released. For now, although testing has been suspended for rheumatoid arthritis and lupus, ocrelizumab is still being tested for relapsing remitting multiple sclerosis (MS).
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Roche Suspends Phase III Trials for Ocrelizumab originally appeared on About.com Arthritis on Wednesday, March 10th, 2010 at 23:59:51. Permalink | Comment | Email this
Bursitis - Fast Facts
 Bursae are small fluid-filled sacs that serve as cushions and reduce friction between bone and other moving parts, such as overlying muscle, tendons, or skin. There are approximately 160 bursae found throughout the body. If a bursa becomes inflamed, the condition is referred to as bursitis.
People whose occupation or leisure activity requires repetitive use of a joint are prone to bursitis. Learn more about the symptoms, diagnosis, and treatment of bursitis in Bursitis - Fast Facts.
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Bursitis - Fast Facts originally appeared on About.com Arthritis on Sunday, March 7th, 2010 at 23:34:44. Permalink | Comment | Email this
Arthritis Can Affect Self-Esteem
 Living with chronic pain and physical limitations can test your confidence and affect your self-esteem. Think about it -- self-esteem is a measure of how you feel about yourself. Your self-esteem gauge is high when you feel you perform well -- whether that be at work, in the home, or during leisure time -- and it's low when you feel you're failing at what's expected of you.
Logically, it's easy to realize how arthritis can be a life-changer and erode self-esteem -- especially in severe cases. Part of the problem -- we compare ourselves to able-bodied people (people without arthritis). Should your self-esteem be based on how well you perform in an able-bodied world or in your real world? Learn more about how chronic pain and limitations test your confidence in Arthritis Can Affect Self-Esteem.
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Arthritis Can Affect Self-Esteem originally appeared on About.com Arthritis on Saturday, March 6th, 2010 at 23:33:55. Permalink | Comment | Email this
Types of Arthritis: Spondyloarthropathies
 Spondyloarthropathy (also known as spondyloarthritis) refers to a group of inflammatory rheumatic diseases with common characteristics that can include inflammation of the spine, eye, gastrointestinal tract, and skin. Other joints can be involved, as can tendons and ligaments near the spine or affected joint.
The following conditions are classified as spondyloarthropathies:
Learn more about each condition in Spondyloarthropathies Explained.
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Types of Arthritis: Spondyloarthropathies originally appeared on About.com Arthritis on Thursday, March 4th, 2010 at 20:22:04. Permalink | Comment | Email this
Has Fear Been a Factor in Your Disease?
 Arthritis is a disease that can cause fear because of its uncertain course. Arthritis can be life-changing and that can be scary. When first diagnosed, there are immediate concerns. How will the disease affect your ability to work, take care of your family, and take care of yourself?
What will it be like to live every day in pain? Will your treatment cause undesirable side effects? Will you get worse and how fast will that occur? Will you lose your independence? Are you going to become disabled? Has fear been a major factor in your disease as you faced these questions about living with arthritis? Share Your Thoughts - Has Fear Been a Factor in Your Disease?
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Has Fear Been a Factor in Your Disease? originally appeared on About.com Arthritis on Sunday, February 28th, 2010 at 23:39:47. Permalink | Comment | Email this
Rheumatoid Arthritis May Affect Aging Process
 Rheumatoid arthritis patients appear to age faster than people without the disease, according to a report in Arthritis Today. After studying the medical records of 755 rheumatoid arthritis patients who were diagnosed between 1955 and 2008, Mayo Clinic researchers discovered that the patients were physically two years older than their actual age at the time of diagnosis. Beyond that point, they aged even more rapidly.
Researchers concluded that for "every 10 years of chronological aging, people with RA physically age 11.4 years." It is known that, in patients with the disease, there is accelerated aging at the cellular level. Is this effect causing an increased risk of mortality in rheumatoid arthritis patients? How are newer rheumatoid arthritis treatments that became available in the last decade or so affecting aging and mortality? Researchers will likely consider those questions going forward.
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Rheumatoid Arthritis May Affect Aging Process originally appeared on About.com Arthritis on Saturday, February 27th, 2010 at 23:58:28. Permalink | Comment | Email this
Higher Prevalence of Arthritis in American Versus Canadian Women
 The prevalence of arthritis and arthritis-attributable activity limitations is higher in the United States than Canada. When broken down according to gender, the prevalence in men was similar for the two countries but higher for American women than Canadian women. According to study results that appear in the March 2010 issue of Arthritis Care & Research, arthritis prevalence was 23.3% for American women compared to 19.6% for Canadian women. American women also had a higher prevalence of arthritis-attributable activity limitations than Canadian women (13% versus 9.2% respectively).
Why the difference? Researchers reported that the higher prevalence for American women may be due to greater obesity and physical inactivity. Controlling your weight and increasing physical activity are important goals for reducing the risk of arthritis and the limitations it causes.
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Higher Prevalence of Arthritis in American Versus Canadian Women originally appeared on About.com Arthritis on Friday, February 26th, 2010 at 23:11:39. Permalink | Comment | Email this
Contrast MRI May Help Differentiate Rheumatoid Arthritis and Psoriatic Arthritis
 MRIs that are enhanced by contrast may help doctors differentiate between rheumatoid arthritis and psoriatic arthritis in the hand and wrist. The two types of arthritis have similar symptoms -- making them hard to differentiate.
According to the March issue of the American Journal of Roentgenology, contrast-enhanced MRI improves the visibility of internal structures. The small study at University Hospital of Turbingen in Germany found a difference in the uptake of contrast after 15 minutes between rheumatoid arthritis and psoriatic arthritis patients. The differentiation may ultimately improve treatment options.
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Contrast MRI May Help Differentiate Rheumatoid Arthritis and Psoriatic Arthritis originally appeared on About.com Arthritis on Sunday, February 21st, 2010 at 23:58:25. Permalink | Comment | Email this
Do You Feel Robbed by Arthritis?
 Do you feel robbed by arthritis? Do you feel the disease has taken something from you that you can't get back? Perhaps the disease forced you to quit your job. Perhaps you chose not to have children because of arthritis. You may be unable to participate in your favorite activity or may have had to give up traveling because of arthritis. You may have lost friends.
Whatever the case -- are you missing out on something and do you feel robbed by arthritis? Share your story here and explain how you adjusted to being robbed. If you have not felt robbed, explain why not.
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Do You Feel Robbed by Arthritis? originally appeared on About.com Arthritis on Sunday, February 21st, 2010 at 23:43:52. Permalink | Comment | Email this
Applying for Social Security Disability Income - Share Your Story
 Have you recently applied for SSDI (Social Security Disability Income)? It can be a frustrating experience -- from not knowing how to begin the application process to waiting what seems like forever to find out if you were approved for benefits.
What circumstances caused you to apply for SSDI? Did you find the application process to be straightforward or unnecessarily complicated? Did you use a lawyer during the process, or handle applying for SSDI by yourself? What was most frustrating about the experience and how could you turn that into advice for others?
We learn from each other and from shared experiences. Share Your Story Here About Applying for Social Security Disability Income.
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Applying for Social Security Disability Income - Share Your Story originally appeared on About.com Arthritis on Thursday, February 18th, 2010 at 23:57:00. Permalink | Comment | Email this
Site: Arthritis Research & Therapy - Latest Articles
Work disability remains a major problem in rheumatoid arthritis in the 2000s: data from 32 countries in the QUEST-RA study
IntroductionWork disability is a major consequence of rheumatoid arthritis (RA), associated not only with traditional disease activity variables, but also more significantly with demographic, functional, occupational, and societal variables. Recent reports suggest that the use of biologic agents offers potential for reduced work disability rates, but the conclusions are based on surrogate disease activity measures derived from studies primarily from Western countries.
Methods:
The Quantitative Standard Monitoring of Patients with RA (QUEST-RA) multinational database of 8,039 patients in 86 sites in 32 countries, 16 with high gross domestic product (GDP) (>24K U.S dollars (USD) per capita) and 16 low-GDP countries (<11K USD), was analyzed for work and disability status at onset and over the course of RA, and clinical status of patients who continued working or had stopped working in high-GDP vs. low-GDP countries according to all RA Core Data Set measures. Associations of work disability status with RA Core Data Set variables and indices were analyzed using descriptive statistics and regression analyses.
Results:
At the time of first symptoms, 86% of men (range 57%-100% among countries) and 64% (19%-87%) of women <65 years were working. More than one-third (37%) of these patients reported subsequent work disability because of RA. Among 1,756 patients whose symptoms had began during the 2000s, the probability of continuing to work was 80% (95% confidence interval (CI) 78%-82%) at 2 years and 68% (95% CI 65%-71%) at 5 years, with similar patterns in high-GDP and low-GDP countries. Patients who continued working vs. stopped working had significantly better clinical status for all clinical status measures and patient self-report scores, with similar patterns in high-GDP and low-GDP countries. However, patients who had stopped working in high-GDP countries had better clinical status than patients who continued working in low-GDP countries. The most significant identifier of work disability in all subgroups was Health Assessment Questionnaire (HAQ) functional disability score.
Conclusions:
Work disability rates remain high among people with RA during this millennium. In low-GDP countries, people remain working with high levels of disability and disease activity. Cultural and economic differences between societies affect work disability as an outcome measure for RA.
DNA microarray analysis of rheumatoid arthritis (RA) susceptibility genes identified by genome-wide association studies (GWAS)
In a recent interesting review, Alex Clarke and Timothy J Vyse described the genetics of rheumatic disease. In the past several years, genome-wide association studies (GWASs) have led to the identification of 6 high-risk rheumatoid arthritis (RA) susceptibility genes, namely, CD244, PADI4, SLC22A2, PTPN22, CTLA4, and STAT4. In vitro studies using mutant alleles and cultured cells have revealed the individual upregulation of CD244, PADI4, SLC22A2, and PTPN22, however, studies on the expression of RA susceptibility genes in RA patients are rare. Therefore, we investigated the expression of the abovementioned 6 RA susceptibility genes in 112 RA patients by using DNA microarray analysis. This study aims to clarify whether DNA microarray analysis and GWASs produce comparable results with respect to RA susceptibility genes.
Gait changes precede overt arthritis and strongly correlate with symptoms and histopathological events in pristane-induced arthritis.
IntroductionPristane-induced arthritis (PIA) in the rat has been described as an animal model of inflammatory arthritis which exhibits features similar to rheumatoid arthritis in humans, such as a chronic, destructive, and symmetrical involvement of peripheral joints. However, so far little is known about the earliest inflammatory events and their influence on locomotor behaviour during the course of PIA. To investigate this issue a detailed analysis of the pathologic changes occurring during the prodromal and early stages of PIA was performed.
Methods:
Arthritis was induced in DA.rats by injection of 150 micro-l 2,6,10,4-tetramethyl-pentadecane (pristane) at the base of the tail and changes in locomotor behaviour of the affected paws were monitored using the CatWalk quantitative gait analysis system. The pathologic events occurring in the joints of pristane-injected animals were studied before onset, at onset, and during acute phase of arthritis by histological methods.
Results:
Gait analysis revealed that changes in locomotion such as reduced paw print areas and stance phase time are already apparent before the onset of clinically discernible arthritis symptoms (erythema, paw swelling) and correlate with PIA scores. In agreement with these findings, inflammatory tenosynovitis could be observed by histology already before the onset of erythema and swelling of the respective paws. In the most heavily affected rats also irregularities in step sequence patterns occurred prior to disease onset. A kinetic analysis of clinical and histological findings demonstrated that gait changes precede the pathological changes occurring during the acute phase of pristane-induced arthritis.
Conclusions:
Gait analysis allows for pinpointing the initial inflammatory changes in experimental arthritis models such as pristane-induced arthritis. Analysis of early clinically relevant symptoms in arthritis models may facilitate the search for novel therapeutics to interfere with pain, inflammation and joint destruction in patients suffering from inflammatory arthritis.
Automated evaluation of autoantibodies on human epithelial-2 cells as an approach to standardize cell-based immunofluorescence tests
IntroductionAnalysis of autoantibodies (AAB) by indirect immunofluorescence (IIF) is a basic tool for the serological diagnosis of systemic rheumatic disorders. Automation of AAB IIF reading including pattern recognition may improve intra- and inter-laboratory variability and meet the demand for cost-effective assessment of large numbers of samples. Comparing automated and visual interpretation, the usefulness for routine laboratory diagnostics was investigated.
Methods:
Autoantibody detection by IIF on human epithelial-2 (HEp-2) cells was conducted in a total of 1222 consecutive sera of patients with suspected systemic rheumatic diseases from a university routine laboratory (n=924) and a private referral laboratory (n=298). IIF results from routine diagnostics were compared with a novel automated interpretation system.
Results:
Both diagnostic procedures showed a very good agreement in detecting AAB (kappa=0.828) and differentiating respective immunofluorescence patterns. Only 98 (8.0%) of 1222 sera demonstrated discrepant results in the differentiation of positive from negative samples. The contingency coefficient of Chi-square statistics was 0.646 for the university laboratory cohort with an agreement of 93.0% and 0.695 for the private laboratory cohort with an agreement of 90.6%, P<0.0001, respectively. Comparing immunofluorescence patterns, 111 (15.3%) sera yielded differing results.
Conclusions:
Automated assessment of AAB by IIF on HEp-2 cells using an automated interpretation system is a reliable and robust method for positive/negative differentiation. Employing novel mathematical algorithms, automated interpretation provides reproducible detection of specific immunofluorescence patterns on HEp-2 cells. Automated interpretation can reduce drawbacks of IIF for AAB detection in routine diagnostics providing more reliable data for clinicians.
Circulating surfactant protein -D is low and correlates negatively with systemic inflammation in early, untreated rheumatoid arthritis
IntroductionSurfactant protein D (SP-D) is a collectin with immuno-regulatory functions, which may depend on oligomerization. Anti-microbial and anti-inflammatory properties have been attributed to multimeric SP-D variants, while trimeric subunits per se have been suggested to enhance inflammation. Previously, we reported low circulating SP-D in early rheumatoid arthritis (RA), and the present investigation aims to extend these data by serial SP-D serum measurements, studies on synovial fluid, SP-D size distribution and genotyping in patients with early RA.
Methods:
One-hundred-and-sixty DMARD naive RA patients with disease duration less than 6 months were studied prospectively for 4 years (CIMESTRA trial) including disease activity measures (C-reactive protein, joint counts and Health Assessment Questionnaire (HAQ) score), autoantibodies, x-ray findings and SP-D. SP-D was quantified by enzyme-linked immunosorbent assay (ELISA) and molecular size distribution was assessed by gel filtration chromatography. Further, SP-D Met11Thr single nucleotide polymorphism (SNP) analysis was performed.
Results:
Serum SP-D was significantly lower in RA patients at baseline compared with healthy controls (p<0.001). SP-D increased slightly during follow-up (p<0.001), but was still subnormal at 4 years after adjustment for confounders (p<0.001). SP-D in synovial fluid was up to 2.5-fold lower than in serum. While multimeric variants were detected in serum, SP-D in synovial fluid comprised trimeric subunits only. There were no significant associations between genotype distribution and SP-D. Baseline SP-D was inversely associated to CRP and HAQ score. A similar relationship was observed regarding temporal changes in SP-D and CRP (0-4 years). SP-D was not associated to x-ray findings.
Conclusions:
This study confirms that circulating SP-D is persistently subnormal in early and untreated RA despite a favourable therapeutic response obtained during 4-years follow-up. SP-D correlated negatively to disease activity measures, but was not correlated with x-ray progression or SP-D genotype. These observations suggest that SP-D is implicated in RA pathogenesis at the protein level. The exclusive presence of trimeric SP-D in affected joints may contribute to the maintenance of joint inflammation.Trial registration (j.nr NCT00209859).
TRAF1/C5 polymorphism is not associated with increased mortality in rheumatoid arthritis; two large longitudinal studies
IntroductionRecently an association between a genetic variation in TRAF1/C5 and mortality from sepsis or cancer was found in rheumatoid arthritis (RA). The most prevalent cause of death, cardiovascular disease, may have been missed in that study, since patients were enrolled at an advanced disease stage. Therefore, we used an inception cohort of RA patients to investigate the association between TRAF1/C5 and cardiovascular mortality, and replicate the findings on all-cause mortality. As TRAF1/C5 associated mortality may not be restricted to RA, we also studied a large cohort of non-RA patients.
Methods:
615 RA patients from the Leiden Early Arthritis Clinic (EAC) (mean follow-up 7.6 years) were genotyped for rs10818488. In addition 5634 persons enrolled in the PROspective Study of Pravastatin in the Elderly at Risk (mean follow-up 3.2 years) were genotyped for rs2416808 (R2 >0.99 with rs10818488). The life/death status was determined and for the deceased persons the cause of death was ascertained. Cox proportional hazards and regression models were used to assess hazard ratios (HR) and 95% confidence intervals (CI).
Results:
Seventy-seven RA patients died. The main death causes in RA patients were cardiovascular diseases (37.7%), cancer (28.6%) and death due to infections (9.1%). No association was observed between the rs10818488 susceptible genotype AA and cardiovascular mortality (HR 1.08 95%CI 0.54 to 2.15) and all-cause mortality (HR 0.81 95%CI 0.27 to 2.43). Similar findings were observed for rs2416808 susceptible genotype GG in the non-RA cohort (HR 0.99; 95%CI 0.79 to 1.25 and HR 0.89; 95%CI 0.64 to 1.25, respectively).
Conclusions:
The TRAF1/C5 region is not associated with an increased mortality risk.
Diagnostic value of anti-cyclic citrullinated peptides and association with HLA-DRB1 shared epitope alleles in African rheumatoid arthritis patients
IntroductionTo examine the diagnostic performance of autoantibodies against citrullinated peptides/proteins (ACPA) and to determine the prevalence of HLA-DRB1 shared epitope alleles (SE) in African patients with rheumatoid arthritis (RA).
Methods:
Serum levels of anti-cyclic citrullinated peptides antibodies (anti-CCP2, anti-CCP3), IgM and IgA rheumatoid factors (RF) were measured by enzyme-linked immunosorbent assay in the serum of 56 consecutive RA patients regularly followed in the Rheumatology Unit of Yaounde, Cameroon. Genotyping of HLA-DRB1 alleles was performed by polymerase chain reaction and hybridization with sequence-specific oligonucleotide probes on microbeads arrays. 51 patients with other inflammatory rheumatic diseases and 50 healthy individuals were included as controls.
Results:
Anti-CCP2 assay showed the best diagnosis sensitivity (82%) and specificity (98%) with high PPV (96%) and NPV (91%). 30% of RA patients were bearing at least one copy of the HLA-DRB1 shared epitope (SE) compared to 10% and 14% of patients with other inflammatory rheumatic diseases and healthy individuals, respectively. The presence of the SE was associated with the production of ACPA.
Conclusions:
Anti-CCP2 antibodies are useful markers of RA in African patients. In this cohort, the prevalence of the SE is higher in RA patients than in controls but lower than that reported in patients cohorts of European ancestry. The discrepancy between the high prevalence of ACPA-positive patients and the relatively low number of SE-positive cases suggest that, in addition to SE, other genetic factors control the development of ACPA in African RA patients.
The loss of health status in rheumatoid arthritis and the effect of biologic therapy: a longitudinal observational study
IntroductionThe long-term course of rheumatoid arthritis (RA) in terms of health status is not well understood, nor is the degree of effectiveness of biologic therapy in the community. We modeled the progression of loss of health status, and measured incremental costs and effectiveness of biologic therapy in the community.
Methods:
We studied change in function and health status in 18,485 RA patients (135,731 observations) at 6-month intervals for up to 11 years, including a group of 4,911 patients (59,630 observations) who switched to biologic therapy from non-biologic therapy. We measured the SF-36 Physical Component (PCS) and Mental Component (MCS) Summary scales, the EQ-5D health utility scale, and the Health Assessment Questionnaire (HAQ) disability scale; and we calculated treatment and direct medical costs.
Results:
RA onset caused an immediate and substantial reduction in physical but not mental health status. Thereafter, the progression of dysfunction in RA was very slow (HAQ 0.016 units and PCS -0.125 units annually), only slightly worse than the age and sex-adjusted US population. We estimated biologic treatment to improve HAQ by 0.29 units, PCS by 5.3 units, and EQ-5D by 0.05 units over a 10-year period. The estimated incremental 10-year total direct medical cost for this benefit was $159,140.
Conclusions:
Biologic therapy retards RA progression, but its effect is far less than is seen in clinical trials. In the community, cost-effectiveness is substantially less than that estimated from clinical trial data. The study results represent the incremental benefit of adding biologic therapy to optimum non-biologic therapy.
Urokinase-type plasminogen activator and arthritis progression: role in systemic disease with immune complex involvement
IntroductionUrokinase-type plasminogen activator (u-PA) has been implicated in fibrinolysis, cell migration, latent cytokine activation, cell activation, T cell activation, and tissue remodeling, all of which are involved in the development of rheumatoid arthritis. Previously, u-PA has been reported to play a protective role in monoarticular arthritis models involving mBSA as the antigen, but a deleterious role in the systemic polyarticular collagen-induced arthritis (CIA) model. The Aim of the current study is to determine how u-PA might be acting in systemic arthritis models.
Methods:
The CIA model and bone marrow chimeras were used to determine the cellular source of u-PA required for the arthritis development. Gene expression of inflammatory and destructive mediators was measured in joint tissue by quantitiative PCR and protein levels by ELISA. The requirement for u-PA in the type II collagen (CII)-mAb induced arthritis (CAIA) and K/BxN serum transfer arthritis models was determined using u-PA-/- mice. Neutrophilia was induced in the peritoneal cavity using either ovalbumin/anti-ovalbumin, or the complement component C5a.
Results:
u-PA from a bone marrow-derived cell was required for the full development of CIA. The disease in u-PA-/- mice reconstituted with bone marrrow from C57BL/6 mice was indistinguishable from that in C57BL/6 mice, in terms of clincal score, histologic features, and protein and gene expression of key mediators. u-PA-/- mice were resistant to both CAIA and K/BxN serum transfer arthritis development. u-PA-/- mice developed a reduced neutrophilia and chemokine production in the peritoneal cavity following OVA/anti-OVA injection; in contrast, the peritoneal neutrophilia in response to C5a was u-PA independent.
Conclusions:
u-PA is required for the full development of systemic arthritis models involving immune complex formation and deposition. The cellular source of u-PA required for CIA is bone marrow-derived and likely to be of myeloid origin. For immune complex-mediated peritonitis, and perhaps some other inflammatory responses, it is suggested that the u-PA involvement may be upstream of C5a signaling.
Anabolic and catabolic responses of human articular chondrocytes to varying oxygen percentages
IntroductionOxygen is a critical parameter proposed to modulate the functions of chondrocytes ex-vivo as well as in damaged joints. This article investigates the effect of low (more physiological) oxygen percentage on the biosynthetic and catabolic activity of human articular chondrocytes (HAC) at different phases of in vitro culture.
Methods:
HAC expanded in monolayer were cultured in pellets for 2 weeks (Phase I) or up to an additional 2 weeks (Phase II). In each Phase, cells were exposed to 19% or 5% oxygen. Resulting tissues and culture media were assessed to determine amounts of produced/released proteoglycans and collagens, metalloproteinases (MMPs), collagen degradation products and collagen fibril organization using biochemical, (immuno)-histochemical, gene expression and scanning electron microscopy analyses. In specific experiments, the hypoxia-inducible factor-1 (HIF-1) inhibitor cadmium chloride was supplemented in the culture medium to assess the involvement of this pathway.
Results:
Independent from the oxygen percentage during expansion, HAC cultured at 5%O2 (vs 19%O2) during Phase I accumulated higher amounts of glycosaminoglycans and type II collagen and expressed reduced levels of MMP-1 and MMP-13 mRNA and protein. Switching to 19% oxygen during Phase II resulted in reduced synthesis of proteoglycan and collagen, increased release of MMPs, accumulation of type II collagen fragments and higher branching of collagen fibrils. In contrast, reducing O2 during Phase II resulted in increased proteoglycan and type II collagen synthesis and reduced expression and release of MMP-13 mRNA and protein. Supplementation of cadmium chloride during differentiation culture at 5%O2 drastically reduced the up-regulation of type II collagen and the down-regulation of MMP-1 mRNA.
Conclusions:
The application of more physiologic oxygen percentage during specific phases of differentiation culture enhanced the biosynthetic activity and reduced the activity of catabolic enzymes implicated in cartilage breakdown. Modulation of the oxygen percentage during HAC culture may be used to study pathophysiological events occurring in osteoarthritis and to enhance properties of in vitro engineered cartilaginous tissues.
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