ObjectiveTo compare the gene expression patterns of synovial cells from inflamed or normal/reactive areas of synovial membrane obtained from the same patient with osteoarthritis (OA).MethodsAt the time of total knee replacement, synovial tissues were obtained from 12 patients with knee OA. The inflammation status of the synovial membrane was characterized according to macroscopic criteria and classified as normal/reactive or inflamed. Biopsy samples were cultured separately for 7 days. Microarray gene expression profiling was performed on normal/reactive and inflamed areas. Western blot and immunohistochemistry were used to confirm the identified genes that were differentially expressed.ResultsWe identified 896 genes that were differentially expressed between normal/reactive and inflamed areas. The key pathways were related to inflammation, cartilage metabolism, Wnt signaling, and angiogenesis. In the inflammation network, the genes TREM1 and S100A9 were strongly up-regulated. The genes MMP3, MMP9, CTSH (cathepsin H), and CTSS (cathepsin S) were significantly up-regulated in the cartilage catabolism pathway, while the most up-regulated anabolism enzyme gene was HAS1. In the Wnt signaling pathway, the genes for Wnt-5a and low-density lipoprotein receptor–related protein 5 were up-regulated, while the gene FZD2 and the gene for Dkk-3 were down-regulated. Finally, STC1, which codes for a protein involved in angiogenesis, was identified as the most up-regulated gene in inflamed compared with normal/reactive areas.ConclusionThis study is the first to identify different expression patterns between 2 areas of the synovial membrane from the same patient. These differences concern several key pathways involved in OA pathogenesis. This analysis also provides information regarding new genes and proteins as potential targets of treatment.

During the osteoarthritis (OA) process, activation of immune systems, whether innate or adaptive, is strongly associated with low-grade systemic inflammation. This process is initiated and driven in the synovial membrane, especially by synovium cells, themselves previously activated by damage-associated molecular patterns (DAMPs) released during cartilage degradation. These fragments exert their biological activities through pattern recognition receptors (PRRs) that, as a consequence, induce the activation of signaling pathways and beyond the release of inflammatory mediators, the latter contributing to the vicious cycle between cartilage and synovial membrane. The primary endpoint of this review is to provide the reader with an overview of these many molecules categorized as DAMPs and the contribution of the latter to the pathophysiology of OA. We will also discuss the different strategies to control their effects. We are convinced that a better understanding of DAMPs, their receptors, and associated pathological mechanisms represents a decisive issue for degenerative joint diseases such as OA.

Data suggest that CT and MR arthrography have similar diagnostic performance for the evaluation of rotator cuff tendon tears.

Objective. This study was undertaken to identify new biomarkers of osteoarthritis (OA) by proteomics analysis and to develop specific immunoassays to detect and quantify them.Methods. Proteomics analysis was performed in urine samples from 10 women (mean ؎ SD age 76.0 ؎ 5.0 years) undergoing knee replacement surgery due to severe OA and 5 healthy women (mean ؎ SD age 25.6 ؎ 2.6 years). Protein content was analyzed by 2-dimensional differential gel electrophoresis. Protein spots that exhibited an OA:control abundance ratio of >1.5 were identified by mass spectrometry. Specific enzyme-linked immunosorbent assays were developed and validated in serum obtained from 236 healthy subjects ages 20-64 years and from 76 patients with severe radiologic knee OA (mean ؎ SD age 68.8 ؎ 11.9 years). Immunohistochemical analysis was performed on articular cartilage from tibial plateaus.Results. Thirteen proteins within spots that were significantly modified between groups were identified. Two peptides of fibulin 3, named Fib3-1 and Fib3-2, were of particular interest. Two antisera directed against these peptides were used to develop immuno- Osteoarthritis (OA) is a progressive disorder characterized by synovial inflammation, bone remodeling, and degradation of the extracellular matrix of articular cartilage (1,2). Currently, the diagnosis of OA is based on clinical and radiographic changes which occur late in disease progression. This method does not allow early detection of structural damage, and it is cumbersome to use in daily practice. Some of the available imaging methods lack reproducibility and sensitivity, and thus long-term followup of a large population is required to demonstrate the efficacy of a drug. This constitutes an impediment to new drug development. Therefore, there is an acute need for reliable biochemical markers that can facilitate the diagnosis of OA and inform prognosis, monitoring, and therapeutic strategies for the disease.Biochemical markers of bone, synovium, or cartilage turnover have been proposed as tools for the diagnosis and prognosis of OA and for the monitoring of OA treatment (3-5). The following 5 serum and urinary biomarkers are receiving increasing attention: serum hyaluronic acid (HA), serum cartilage oligomeric matrix protein (COMP), urinary C-telopeptide of type II colSupported by a grant from the government of the Walloon Region of Belgium.

The normalisation of Coll2-1 levels 3 months after surgery indicates that Coll2-1 is a disease-specific marker that is sensitive to the structural changes occurring in a single joint. Furthermore, the immunohistochemical findings are consistent with the concept that the major source of serum Coll2-1 is the damaged articular cartilage. Finally, serum MPO levels decreased after joint replacement indicating that neutrophil activation occurs in OA joints, even in the late stage of the disease.

IntroductionThis work aimed at comparing the production of inflammatory and pro- and anti-angiogenic factors by normal/reactive (N/R) or inflammatory (I) areas of the osteoarthritic synovial membrane. The effects of interleukin (IL)-1β and chondroitin sulfate (CS) on the expression of pro- and anti-angiogenic factors by synovial fibroblasts cells (SFC) were also studied.MethodsBiopsies from N/R or from I areas of osteoarthritic synovial membrane were collected at the time of surgery. The inflammatory status of the synovial membrane was characterized by the surgeon according to macroscopic criteria, including the synovial vascularization, the villi formation and the hypertrophic aspect of the tissue. We assessed the expression of CD45, von Willebrand factor and vascular endothelial growth factor (VEGF) antigen by immunohistochemistry in both N/R and I biopsies. The production of IL-6, -8, VEGF and thrombospondin (TSP)-1 by N/R or I synovial cells was quantified by ELISA. SFC were cultured in the absence or in the presence of IL-1β (1 ng/ml) and with or without CS (10, 50, 200 μg/ml). Gene expression of pro-angiogenic factors (VEGF, basic fibroblast growth factor (bFGF), nerve growth factor (NGF), matrix metalloproteinase (MMP)-2 and angiopoietin (ang)-1) and anti-angiogenic factors (vascular endothelial growth inhibitor (VEGI), TSP-1 and -2) were determined by real time RT-PCR. Production of VEGI and TSP-1 was also estimated by ELISA.ResultsImmunohistochemistry showed the increase of lymphocyte infiltration, vascular density and VEGF expression in I compared to N/R synovial biopsies. Synovial cells from I areas produced more IL-6, IL-8 and VEGF but less TSP-1 than cells isolated from N/R synovial biopsies. The expression of pro-angiogenic factors by SFC was stimulated by IL-1β. A time dependent regulation of the expression of anti-angiogenic factor genes was observed. IL-1β stimulated the expression of anti-angiogenic factor genes but inhibited it after 24 h. CS reversed the inhibitory effect of IL-1β on anti-angiogenic factors, VEGI and TSP-1.ConclusionsWe demonstrated that synovial biopsies from I areas expressed a pro-angiogenic phenotype. IL-1β induced an imbalance between pro- and anti-angiogenic factors in SFC and CS tended to normalize this IL-1β-induced imbalance, providing a new possible mechanism of action of this drug.

No abstract

This study assessed the diagnostic effectiveness of multidetector spiral CT arthrography (MDCTa) in detecting hyaline cartilage abnormalities of the shoulder joint, with correlation to arthroscopy. Shoulder MDCTa images prospectively obtained in 22 consecutive patients (mean age, 50 years; age range, 23-74 years; 12 female, 10 male) were evaluated for glenohumeral cartilage lesions. Two musculoskeletal radiologists independently analysed the cartilage surfaces of the humeral head and of the glenoid fossa in nine anatomical surface areas. Observations of MDCTa were compared to arthroscopic findings. The sensitivity and specificity of MDCTa for grade 2 (substance loss <50%) or higher and grade 3 (substance loss >or=50%) or higher cartilage lesions, the Spearman correlation coefficient between arthrographic and arthroscopic grading, and K statistics for assessing Intra and Interobserver reproducibility were determined. At MDCTa, sensitivities and specificities ranged between 80% and 94% for the detection of grade 2 or higher cartilage lesions, and between 88% and 98% for the detection of grade 3 or higher cartilage lesions. Spearman correlation coefficients between MDCTa and arthroscopic grading of articular surfaces ranged between 0.532 and 0.651. Interobserver agreement was moderate for grading all articular surfaces (kappa = 0.457), but substantial to almost perfect for detecting lesions with substance loss (kappa, 0.618-0.876). In conclusion, MDCTa is accurate for the study of cartilage surface in the entire shoulder joint. This technique may beneficially impact patient's management by means of selecting the proper treatment approach.