Although the osteoprotegerin (OPG)/RANK/RANKL system is the main modulator of bone remodeling, it remains unclear whether it is regulated in cartilage during osteoarthritis (OA). The aim of this ...study was to examine whether nonsteroidal antiinflammatory drug (NSAID) treatment modulates the synthesis of OPG and RANKL in the cartilage of patients with OA, and to investigate whether prostaglandin E(2) (PGE(2)) modifies this system in human OA chondrocytes in culture.
A 3-month clinical trial was carried out in 20 patients with severe knee OA, all of whom were scheduled to undergo knee replacement surgery. Ten of these patients were treated with celecoxib, and the other 10 patients, who did not want to be treated, served as the control group. After surgery, cartilage was processed for molecular biology studies. We also used human OA chondrocytes to examine the effects of PGE(2) on OPG/RANKL synthesis, examining which surface receptors were affected by PGE(2).
In patients with OA, celecoxib decreased RANKL synthesis in the cartilage, thereby increasing the OPG:RANKL ratio. In human OA chondrocytes in culture, PGE(2) elicited a dose- and time-dependent increase in the synthesis of RANKL, the extent of which was greater than that of OPG. Confocal microscopy revealed that PGE(2) induced RANKL transport to the cell membrane. Only EP2/EP4 agonists reproduced the effects of PGE(2) on OPG and RANKL induction.
Long-term NSAID treatment inhibited the resorptive signal synthesized by chondrocytes. In vitro, PGE(2) regulated the expression and release of these key mediators of bone metabolism by articular chondrocytes. The role of OPG/RANK/RANKL in OA cartilage metabolism is still unknown, although the synthesis of these proteins would enable the cartilage to control the activity of subchondral bone cells.
This review emphasizes the safety profile of intra-articular hyaluronic acid treatment of knee
osteoarthritis, as well as its moderate but real efficacy on symptoms, which is in the same
range than ...other pharmacological modalities used in this indication. Effectiveness of intraarticular
hyaluronic acid has also been highlighted based on ‘real-life’ data, together with the
clinical benefit of systematic repeated treatment cycles, and the influence of the molecular
weight of hyaluronic acid on treatment outcome. These aspects should be particularly helpful
to clinicians when making personalized care decisions.
Platelet activating factor (PAF) is a potent mediator of allergic and inflammatory reactions in different pathological conditions. During recent years there has been increasing evidence that PAF can ...play an important role in the pathogenesis of arthritis. The PMN proteinases make an important contribution to the final tissue joint destruction in arthritis. In a rabbit model of acute crystal arthritis, we have compared the anti-inflammatory effect of two new molecules: BN 50727 with anti-PAF activity, and BN 50548 an inhibitor of PMN proteinases. These molecules were administered dissolved in DMSO at doses of 6 mg/kg three times daily i.p., beginning 24 h before the induction of arthritis. Compared with the untreated animals those receiving the drugs, presented a significant diminution in: (1) the synovial fluid volume; (2) the amount of cells infiltrating the joint cavity and the synovial membrane; and (3) the PGE
2 concentration. Furthermore, in both groups of treated rabbits there was a significant decrease in synovial IL-6 concentration and in C-reactive protein serum levels and an important decline of histopathological score. The treatment with BN 50548 induced a significant reduction of TNF levels in the synovial fluid vs DMSO-treated and untreated rabbits. These results further strengthen that in an acute experimental arthritis model, molecules with capacity to antagonize the in vivo action of PAF have an anti-inflammatory effect reflecting an important role for this mediator in the pathogenesis of arthritis. We have also seen that an inhibitor of proteinases is capable of improving the joint inflammation apparently through a decrease in tumor necrosis factor (TNF) and interleukin-6 (IL-6) synovial levels. Furthermore, the proteinase inhibitor treatment preserves the loss of articular proteoglycan content, in an acute arthritis model. In conclusion, BN 50727 and BN 50548, two compounds with PAF antagonist and antiproteinase activity, respectively exert an anti-inflammatory effect in an experimental model of acute urate crystal arthritis, probably due to a decrease in TNFa and IL-6 synthesis.
A woman with selective IgA deficiency and severe ankylosing spondylitis (AS), complicated by intractable peripheral arthritis, is described. Three previous cases of selective IgA deficiency and AS ...have been reported, all of whom had severe AS. It is suggested that selective IgA deficiency is a poor prognostic factor in AS and therefore warrants further investigation to determine the clinical course of such patients.
The present study was undertaken to investigate, if the non-steroidal anti-inflammatory drug (NSAID) piroxicam (CAS 36322-90-4) Fast-Dissolving Dosage Form (FDDF) can be absorbed in the oral mucosa. ...Piroxicam FDDF was administrated under the tongue to rats with an oesophagus ligation (OL) to prevent the drug entering the stomach and in turn its absorption by the classic way. A group of sham-operated (SO) animals received the same piroxicam FDDF dose. After drug administration, a pharmacokinetic study with serial serum sample extractions at 0, 15, 30, 60 and 120 min was performed. It has been found a prompt increase in serum piroxicam levels in OL-rats, which showed different pharmacokinetics from SO-rats. Areas under curve (AUCs) of OL-rat serum piroxicam levels were higher at 15, 30 and 60 min compared to SO-animals. These results indicate that piroxicam FDDF is absorbed in the rat oral mucosa. Moreover, during the first hour, drug absorption by oral mucosa rendered higher piroxicam levels than gastric absorption.
Objective. To determine whether tenidap regulates extracellular matrix metabolism in chronic arthritis.
Methods. Antigen arthritis was induced in the knees of 30 rabbits. Animals were distributed ...into 3 groups: untreated, tenidap‐treated, and diclofenactreated rabbits. Three weeks after disease induction, synovial membranes were extracted and processed for histopathologic examination and detection of type I collagen (CI) and fibronectin (FN) by immunoperoxidase. Simultaneously, we analyzed the in vitro effect of tenidap on healthy synovial cell (SC) proliferation, FN expression and synthesis, and expression of transforming growth factor β1 (TGFβ1) messenger RNA.
Results. Untreated animals showed synovial lining hyperplasia, cellular infiltration at the sublining, and increased deposition of matrix proteins. These findings were not apparent in tenidap‐treated rabbits, where CI and FN had the same distribution as in healthy synovial membranes. In vitro, tenidap inhibited SC proliferation (⩾25 μM) and down‐regulated the expression and synthesis of FN in a dose‐dependent manner (⩾1 μM). This antifibrotic effect was associated with a reduction of TGFβ1 message.
Conclusion. Tenidap down‐regulates the fibroproliferative changes typical of chronic arthritis, an effect that fits the profile of a disease‐modifying agent for rheumatoid arthritis.
We studied the effect of fibronectin (FN) on the course of chronic nephritis (induced by daily injections of ovalbumin) and on the clearance and catabolism of immune complexes in Wistar rats. Rats ...with chronic nephritis were treated with FN (2.5 mg/kg/48 hours) for 15 days after proteinuria was first detected. In rats with untreated nephritis, urinary protein levels increased from 40 ± 22 mg/day (mean ± SD) to 339 ± 68 mg/day during the 15 days of the study (P < 0.0005). This statistically significant increase was not observed in rats treated with FN (mean ± SD 58 ± 46 mg/day to 124 ± 112 mg/day). Rats treated with FN showed a higher total serum protein level than did the untreated animals (mean ± SD 6.4 ± 0.3 gm/dl versus 5.1 ± 0.5 gm/dl; P < 0.0125), as well as a significant reduction in mesangial and glomerular basement membrane deposits. Untreated nephritic rats demonstrated delayed plasma clearance of 125I‐labeled aggregated IgG (plasma half‐life T1/2 3.03 ± 0.6 minutes) and less catabolism of these aggregates at 30 minutes (mean ± SD 15 ± 1.7%) than did the normal rats (T1/2 1.5 ± 0.2 minutes, 22 ± 2.8%, respectively; P < 0.0005). Both parameters were within normal limits in the FN‐treated rats (T1/2 1.6 ± 0.4 minutes, 22 ± 6%, respectively). In vitro, FN induced a significant increase in aggregated IgG catabolism by Kupffer cells and peritoneal macrophages from normal rats. These results show that FN reduces the proteinuria and histologic lesions of chronic nephritis in rats. These beneficial effects of FN could be due to the improved clearance of immune complexes, decreased glomerular deposition, and perhaps, to better renal processing of immune complexes.
Arthritis in beta‐thalassemia minor Górriz, Luis; León, Celso De; Herrero‐Beaumont, Gabriel ...
Arthritis and rheumatism,
October 1983, Letnik:
26, Številka:
10
Journal Article
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