Development Of Cartilage Destruction Research Articles

IMAGING OF COLLAGEN TYPE II TO DETECT (EARLY) CARTILAGE DESTRUCTION IN OSTEOARTHRITIS.

Purpose: Cartilage damage is one of the central hallmarks of osteoarthritis (OA). Classical imaging modalities like X-ray and magnetic resonance imaging, mainly allow the identification of advanced cartilage damage. Development of cartilage destruction is highly variable among OA patients and the detection of early cartilage damage using sensitive molecular imaging tracers will likely facilitate an early diagnosis and more precise monitoring of disease progression. Moreover, this will allow for non-invasive testing of possible new therapeutics.

Immune Contributions to Osteoarthritis.

Mounting evidence supports a role of low-grade inflammation in the pathophysiology of osteoarthritis (OA). We review and discuss the role of synovitis, complement activation, cytokines, and immune cell population in OA. Using newer imaging modalities, synovitis is found in the majority of knees with OA. Complement activation and pro-inflammatory cytokines play a significant role in the development of cartilage destruction and synovitis. Immune cell infiltration of OA synovial tissue by sub-populations of T cells and activated macrophages correlates with OA disease progression and pain. The innate and acquired immune system plays a key role in the low-grade inflammation found associated with OA. Targets of these pathways my hold promise for future disease-modifying osteoarthritis drugs (DMOADs).

OP0024 Synovial Activation Drives Efficacy of Anti-Inflammatory Effects of Adipose-Derived Stem Cells in Experimental OA Which is Reflected by Serum Levels of S100a8/A9

BackgroundSynovitis is evident in a substantial subpopulation of patients with early osteoarthritis (OA). Recently we have shown that adipose derived stem cells (ASC) inhibit synovitis and joint destruction after local...

The matrix metalloproteinases as pharmacological target in osteoarthritis: Statins may be of therapeutic benefit

Osteoarthritis (OA) is a common joint disease; however, current pharmacologic agents for OA are only symptomatic and they can not prevent the disease progression. Matrix metalloproteinases (MMPs) produced by chondrocytes play an important role in the development of cartilage destruction in OA, and agents that can target against MMPs activity may be of therapeutical value. There were reports that statins can inhibit the secretion of MMPs in vitro and in vivo, which were believed to account for the plaque stabilizing effects of statins in the treatment of atherosclerosis. We based our hypothesis on that atherosclerosis possesses some aspects that are similar to that of osteoarthritis, such as inflammation and matrix degradation. Since statins have displayed great benefits in modifying the progression of atherosclerosis via anti-inflammatory and matrix-stabilizing mechanisms, it is conceivable that statins may also prevent the disease progression of osteoarthritis. Further work are needed to verify if statins can protect cartilage from destruction through inhibition of MMP secretion by chondrocytes, and their potential to be used as therapeutic agents in OA should be investigated.

DSC measurement of cartilage destruction caused by septic arthritis

Treatment of a bacterial arthritis is a challenging task for a clinician as inadequate therapy can cause cartilage destruction and can result in severe osteoarthritis of the affected joint. The development of cartilage destruction in septic arthritis is not known in details. The aim of this study was to follow this process by calorimetric method. We induced experimental septic arthritis in knee joints of seven New Zealand rabbits by single inocculation of Staphylococcus aureusOKI 112001 culture (1.5 mL 8·108±5% c.f.u.). The first rabbit died on the 11thday. At that time all the other subjects were made overslept and samples were isolated from the cartilage of the femurs for calorimetric measurement. The DSC scans clearly demonstrated the development of infective structural destruction in cartilage from the first to the tenth day of incubation. In case of healthy control the melting temperatures (T m) were: 49.7, 55 and 63.4°C and the total calorimetric enthalpy change (ΔH) was 0.55 J g-1. After the first day the enthalpy decreased (0.375 J g-1), the first two transition temperature shifted towards higher temperature: 57 and 63.15°C. Up to the fourth day the effect of infection culminated with T mof 49.3, 55.9, 59.4, 62.8°C and further decrease of the ΔH. At the fifth day the effect of infection is culminated in two separable thermal denaturation events (with 55 and 63.3°C T ms) with high jump in ΔHindicating the dramatic change of the structure of rabbit cartilage, so this time elapsed seems to be critical from the point of view of practical clinical relevance too. Between the 7thand 11thdays practically we had same melting temperatures (50 and 63°C) with low (~0.24 J g-1) enthalpy.

Synovial fluid analysis of two groups of proteoglycan epitopes distinguishes early and late cartilage lesions

To investigate whether fragmentation of proteoglycans in arthritis results in domains that have different levels of release from cartilage at different stages of the disease. Two regions of the proteoglycan, the hyaluronan-binding region and the glycosaminoglycan-rich region of the core protein, were measured, by immunoassay, in knee joint synovial fluids of patients with rheumatoid arthritis or reactive arthritis. Synovial fluid concentrations of the glycosaminoglycan-rich region were highest in rheumatoid arthritis patients who had little cartilage damage as determined by radiography, whereas release of the hyaluronan-binding region predominated in patients with advanced cartilage destruction. In reactive arthritis, release of the glycosaminoglycan-rich region predominated. These findings indicate that the hyaluronan-binding region is initially retained in the tissue during the development of cartilage destruction. The combined analysis of these markers offers a new avenue for assessment of the degree of cartilage damage in arthritis.

Degradation of cartilage proteoglycan and collagen by synovial cells: Stimulation by macrophages under activation by phagocytosis, lymphocyte factors, bacterial products or other inflammatory stimuli

When cultured together with dead 35S-labelled cartilage discs or at the surface of [ 3 H]proteoglycan [ 14 C]collagen-coated plates, synovial cells from either arthritic or normal rabbit joints digested both the proteoglycan and the collagen of the substrates after a lag-period of 1–2 days. These digestions were inversely related to the age (number of subculture passages) of the synovial cells and they could be modulated by serum components that were either inhibitory or stimulatory. They were dependent on a protein synthesis by the cells and were paralleled, in young cultures, by the release of collagenase and of a proteoglycan-degrading neutral proteinase. The co-culture of synovial cells with macrophages or their culture with macrophage-conditioned culture media caused a more rapid and more extensive degradation of collagen and proteoglycan due to the stimulation of the synovial cells by a nondialysable macrophage factor. The production of this synovial cell-activating ‘matrix regulatory monokine’ by the macrophage was enhanced by several immunological or inflammatory stimuli such as lymphocyte factors, phagocytosis, asbestos fibres, endotoxin, adjuvant muramyl dipeptide or chemotactic formyl-methionyl peptide, as well as by other membrane-active agents (phorbol myristate acetate, concanavalin A). It is presumed that these interactions are of importance in the development of cartilage destruction in rheumatoid and other chronic inflammatory arthritis.