Objective. Wnt signaling pathway proteins are involved in embryonic development of cartilage and bone, and, interestingly, developmental processes appear to be recapitulated in osteoarthritic (OA) cartilage. The present study was undertaken to characterize the expression pattern of Wnt and Fz genes during experimental OA and to determine the function of selected genes in experimental and human OA.Methods. Longitudinal expression analysis was performed in 2 models of OA. Levels of messenger RNA for genes from the Wnt/-catenin pathway were determined in synovium and cartilage, and the results were validated using immunohistochemistry. Effects of selected genes were assessed in vitro using recombinant protein, and in vivo by adenoviral overexpression.Results. Wnt-induced signaling protein 1 (WISP-1) expression was strongly increased in the synovium and cartilage of mice with experimental OA. Osteoarthritis (OA) results in the destruction of cartilage and bone, ultimately leading to loss of joint function. The cause of the disease is largely unknown, although obesity, genetic factors, and injury have all been associated with increased risk of OA (1,2). Although it is likely that in most cases the initial events leading to OA occur within the cartilage or subchondral bone (3,4), the synovial tissue of many OA patients shows a changed morphology, with a marked inflammatory phenotype (5,6).
Wnt-16 andLoss of articular cartilage extracellular matrix is thought to be mediated by matrix metalloproteinases (MMPs) and aggrecanases (ADAMTS-4 and ADAMTS-5), which are likely the most important groups of enzymes in the breakdown of extracellular
Dendritic cells (DCs) are specialized APCs that can be activated upon pathogen recognition as well as recognition of endogenous ligands, which are released during inflammation and cell stress. The recognition of exogenous and endogenous ligands depends on TLRs, which are abundantly expressed in synovial tissue from rheumatoid arthritis (RA) patients. Furthermore TLR ligands are found to be present in RA serum and synovial fluid and are significantly increased, compared with serum and synovial fluid from healthy volunteers and patients with systemic sclerosis and systemic lupus erythematosus. Identification of novel endogenous TLR ligands might contribute to the elucidation of the role of TLRs in RA and other autoimmune diseases. In this study, we investigated whether five members of the small heat shock protein (HSP) family were involved in TLR4-mediated DC activation and whether these small HSPs were present in RA synovial tissue. In vitro, monocyte-derived DCs were stimulated with recombinant αA crystallin, αB crystallin, HSP20, HSPB8, and HSP27. Using flow cytometry and multiplex cytokine assays, we showed that both αA crystallin and HSPB8 were able to activate DCs and that this activation was TLR4 dependent. Furthermore, Western blot and immunohistochemistry showed that HSPB8 was abundantly expressed in synovial tissue from patients with RA. With these experiments, we identified sHSP αA crystallin and HSPB8 as two new endogenous TLR4 ligands from which HSPB8 is abundantly expressed in RA synovial tissue. These findings suggest a role for HSPB8 during the inflammatory process in autoimmune diseases such as RA.
Subchondral bone and the synovium play an important role in the initiation and progression of OA. MRI often permits an early detection of synovial hypertrophy and bone marrow lesions, both of which can precede cartilage damage. Newer imaging modalities including CT osteoabsorptiometry and hybrid SPECT-CT have underlined the importance of bone in OA pathogenesis. The subchondral bone in OA undergoes an uncoupled remodelling process, which is notably characterized by macrophage infiltration and osteoclast formation. Concomitant increased osteoblast activity leads to spatial remineralization and osteosclerosis in end-stage disease. A plethora of metabolic and mechanical factors can lead to synovitis in OA. Synovial tissue is highly vascularized and thus exposed to systemic influences such as hypercholesterolaemia or low grade inflammation. This review aims to describe the current understanding of synovitis and subchondral bone pathology and their connection in OA.
A discreet number of YouTube videos on knee arthrocentesis appeared to be suitable for application in a Web-based format for medical students, fellows, and residents. The low-average mean global score for overall educational value suggests an improvement of future video-based instructional materials on YouTube would be necessary before regular use for teaching could be recommended.
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