Conclusion.These data demonstrate the presence of TLRs in human articular cartilage. The suppressive effects of LPS on cartilage biosynthetic activity are dependent on the presence of TLR-4, are governed, at least in part, by an up-regulation of IL-1␤, and are mediated by p38 kinase. These in vitro data indicate an anti-anabolic effect of TLR-4 in articular chondrocytes that may hamper cartilage repair in various joint diseases.

Objective. To investigate the relationship between increased discoidin domain receptor 2 (DDR-2) expression and cartilage damage in osteoarthritis (OA).Methods. Full-thickness cartilage tissue samples from 16 human knee joints were obtained and the grade of cartilage damage was evaluated according to the Mankin scale. Expression of DDR-2, matrix metalloproteinase 13 (MMP-13), and MMP-derived type II collagen fragments was visualized immunohistochemically. Moreover, upon stimulation with either type II collagen or gelatin, levels of DDR-2 and MMP-13 messenger RNA (mRNA) in primary human articular chondrocytes were assessed by real-time polymerase chain reaction.Results. Immunohistochemical analysis showed an increase in DDR-2 expression in human articular cartilage, which was correlated with the degree of tissue damage. In parallel, the extent of MMP-13 and type II collagen breakdown products was elevated as a function of increased DDR-2 expression and cartilage damage. Furthermore, in vitro experiments revealed an upregulation of both DDR-2 and MMP-13 mRNA in human articular chondrocytes after stimulation with type II collagen.Conclusion. Our data indicate that 3 factors, DDR-2 expression, MMP-13 expression, and the degree of cartilage damage, are linked, such that DDR-2 promotes tissue catabolism, and tissue degradation promotes DDR-2 up-regulation and activation. Thus, the perpetuation of DDR-2 expression and activation can be seen as a vicious circle that ultimately leads to cartilage destruction in OA.Osteoarthritis (OA) is considered to be the most common rheumatic disorder (1). The disease has been associated with a variety of distinct risk factors, but with similar clinical outcomes regardless of the postulated risk factor. Although understanding of the pathogenesis of OA has evolved considerably over the past years, the molecular mechanisms are largely unknown. Nevertheless, alterations that occur during cartilage degeneration, eventually leading to OA, are remarkably similar regardless of the etiology. The pathologic events are characterized by proteoglycan loss, followed by type II collagen degradation, and ultimately by localized or complete destruction of articular cartilage matrix (2). Thus, elucidating a common pathway in OA development leading to cartilage degeneration would provide new insight into the pathogenesis of OA.Our recent findings provide evidence for the existence of such a pathway in articular chondrocytes.

In this murine model of TNFalpha-mediated arthritis, the expression of GDF-5 and BMP-7 is regulated differentially in articular cartilage and synovium. In articular cartilage, the down-regulation of GDF-5 and BMP-7, which function to maintain matrix integrity, could potentially compromise tissue repair, whereas in synovium, the increased expression of GDF-5 and BMP-7 might contribute to synovial hypertrophy.

On the basis of histopathological changes of DIP and PIP joints, this investigation demonstrates the validity of x-ray examinations and supports the use of plain radiography in the diagnosis of hand OA and in the classification of hand OA in clinical trials.

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