Nonsteroidal antiinflammatory drugs and prostaglandin E(2) modulate the synthesis of osteoprotegerin and RANKL in the cartilage of patients with severe knee osteoarthritis
| Autor: | Juan Moreno-Rubio, Gabriel Herrero-Beaumont, Lidia Tardio, M. Angeles Alvarez-Soria, Raquel Largo |
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| Rok vydání: | 2010 |
| Předmět: |
musculoskeletal diseases
medicine.medical_specialty Prostaglandin E2 receptor Immunology Gene Expression Osteoarthritis Cartilage metabolism Severity of Illness Index Dinoprostone Bone remodeling Chondrocytes Rheumatology Osteoprotegerin Internal medicine medicine Immunology and Allergy Humans Receptors Prostaglandin E Pharmacology (medical) Prostaglandin E2 Cells Cultured Aged Aged 80 and over Sulfonamides biology Cyclooxygenase 2 Inhibitors Dose-Response Relationship Drug business.industry Cartilage Anti-Inflammatory Agents Non-Steroidal RANK Ligand Osteoarthritis Knee medicine.disease Immunohistochemistry Endocrinology medicine.anatomical_structure RANKL Celecoxib biology.protein Pyrazoles lipids (amino acids peptides and proteins) business medicine.drug Signal Transduction |
| Zdroj: | Arthritis and rheumatism. 62(2) |
| ISSN: | 0004-3591 |
| Popis: | Objective 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 E2 (PGE2) modifies this system in human OA chondrocytes in culture. Methods 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 PGE2 on OPG/RANKL synthesis, examining which surface receptors were affected by PGE2. Results In patients with OA, celecoxib decreased RANKL synthesis in the cartilage, thereby increasing the OPG:RANKL ratio. In human OA chondrocytes in culture, PGE2 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 PGE2 induced RANKL transport to the cell membrane. Only EP2/EP4 agonists reproduced the effects of PGE2 on OPG and RANKL induction. Conclusion Long-term NSAID treatment inhibited the resorptive signal synthesized by chondrocytes. In vitro, PGE2 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. |
| Databáze: | OpenAIRE |
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