Search

Osteoarthritis (OA) or osteoarthrosis? Reports in the last decade have suggested that human OA-affected chondrocytes and activated macrophages share the release of similar inflammatory mediators. In spite of the superinduction of inflammatory mediators by OA-affected chondrocytes, the unique architecture of cartilage (avascular, aneural and alymphatic) when inflamed at the molecular level, does not qualify for the typical definition of inflammation (redness and swelling with heat and pain—rubor et tumor cum calore et dolor) due to the semantics and the history of the word ‘inflammation’. The genomic revolution provides access to tools for examining a single event in the context of the whole genome. Use of this facility can lead to new ways of understanding complex pathophysiological conditions such as inflammation. From research laboratories to clinical settings, inflammation is now perceived differently although the molecular events remain the same. The present editorial highlights semantic issues using one example of an ‘inflammatory disease’: OA.

Objective We have demonstrated in bovine chondrocytes that nitric oxide (NO) mediates IL1 dependent apoptosis under conditions of oxidant stress. This process is accompanied by activation of c-Jun NH2-terminal kinase (JNK; also called stress-activated protein kinase). In these studies we examined activation of JNK in explant cultures of human osteoarthritic cartilage obtained at joint replacement surgery and we characterized the role of peroxynitrite to act as an upstream trigger.Design A novel technique to isolate chondrocyte proteins (

Objective: To examine the effects of non-steroidal anti-inflammatory drugs (NSAIDS) on nitric oxide (NO) and prostaglandin E 2 (PGE 2 ) production in chondrocytes from three different species. Methods: We have estimated NO production by Griess method, and PGE 2 by RIA from the supernatant of articular cartilage obtained from osteoarthritis joints (OA-affected cartilage), rat chondrosarcomas (in ex vivo conditions) and bovine chondrocytes (stimulated with cytokines+endotoxin in in vitro conditions) in the presence or absence of aspirin, indomethacin, sodium salicylate, tenidap and glucocorticoids. Results: NO, which was spontaneously released in ex vivo conditions by OA-affected cartilage and rat chondrosarcomas (maintained in vivo ), was susceptible to inhibition by pharmacologically relevant concentrations of aspirin, sodium salicylate and tenidap, but not to concentrations of indomethacin or glucocorticoids that significantly inhibited PGE 2 production under the same conditions. Similarly, the production of NO by bovine chondrocytes grown in monolayer cultures that had been stimulated with cytokines+endotoxins ( in vitro ) to release both No and PGE 2 (at 48–72 h post stimulation), were inhibited by aspirin, sodium salicylate and tenidap, but not by indomethacin or glucocorticoids at concentrations sufficient to inhibit PGE 2 production. Inhibition of NO in the cytokines+endotoxin stimulated bovine chondrocytes (like the human OA-affected cartilage) augmented PGE 2 production. Conclusion: These experiments demonstrate that NO production by chondrocytes across species show a similar profile of susceptibility to inhibition by selected anti-inflammatory drugs. The insensitivity of NO production to glucocorticoids is an important characteristic of these cells that merits further investigation.

Summary Gene transfer to chondrocytes followed by intra-articular transplantation may allow for functional modulation of chondrocyte biology and enhanced repair of damaged articular cartilage. We chose to examine the loss of chondrocytes transduced with a recombinant adenovirus containing the gene for Escherichia coli α -galactosidase (Ad.RSVntlacZ), followed by transplantation into deep and shallow articular cartilage defects using New Zealand White rabbits as an animal model. A type I collagen matrix was used as a carrier for the growth of the transduced chondrocytes and to retain the cells within the surgically created articular defects. Histochemical analysis of matrices recovered from the animals 1, 3 and 10 days after implantation showed the continued loss of lacZ positive chondrocytes. The number of cells recovered from the matrices was also compared with the initial innoculum of transduced cells present within the matrices at the time of implantation. The greatest loss of transduced cells was observed in the first 24 h after implantation. The numbers of transduced cells present within the matrices were relatively constant between 1 and 3 days postimplantation, but had progressively declined by 10 days postimplantation. These results suggest that transduction of chondrocytes followed by intra-articular transplantation in this rabbit model may enable us to examine the biological effects of focal transgenic overexpression of proteins involved in cartilage homeostasis and repair.