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12. The protective effect of licofelone on experimental osteoarthritis is correlated with the downregulation of gene expression and protein synthesis of several major cartilage catabolic factors: MMP-13, cathepsin K and aggrecanases

Author

Pelletier, J. P., Boileau, C., Boily, M., Brunet, J., Mineau, F., Geng, C., Pascal Reboul, Laufer, S., Lajeunesse, D., Martel-Pelletier, J., Centre Hospitalier de l'Université de Montréal (CHUM), Université de Montréal (UdeM), and Eberhard Karls Universität Tübingen = Eberhard Karls University of Tuebingen

Subjects
[SDV.MHEP.RSOA]Life Sciences [q-bio]/Human health and pathology/Rhumatology and musculoskeletal system, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], [SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology
Abstract

International audience; This study sought to evaluate the levels of mRNA expression and protein synthesis of MMP-13, cathepsin K, aggrecanase-1 (ADAMTS-4), aggrecanase-2 (ADAMTS-5) and 5-lipoxygenase (5-LOX) in cartilage in the experimental anterior cruciate ligament (ACL) dog model of osteoarthritis (OA), and to examine the effects of treatment with licofelone, a 5-lipoxygenase (LOX)/ cyclooxygenase (COX) inhibitor, on the levels of these catabolic factors. Sectioning of the ACL of the right knee was performed in three experimental groups: group 1 received no active treatment (placebo group); and groups 2 and 3 received therapeutic concentrations of licofelone (2.5 or 5.0 mg/kg/day orally, respectively) for 8 weeks, beginning the day following surgery. A fourth group consisted of untreated dogs that were used as normal controls. Specimens of cartilage were selected from lesional areas of OA femoral condyles and tibial plateaus, and were processed for real-time quantitative PCR and immunohistochemical analyses. The levels of MMP-13, cathepsin K, ADAMTS-4, ADAMTS-5 and 5-LOX were found to be significantly increased in OA cartilage. Licofelone treatment decreased the levels of both mRNA expression and protein synthesis of the factors studied. Of note was the marked reduction in the level of 5-LOX gene expression. The effects of the drug were about the same at both tested dosages. In vivo treatment with therapeutic dosages of licofelone has been found to reduce the degradation of OA cartilage in experimental OA. This, coupled with the results of the present study, indicates that the effects of licofelone are mediated by the inhibition of the major cartilage catabolic pathways involved in the destruction of cartilage matrix macromolecules. Moreover, our findings also indicate the possible auto-regulation of 5-LOX gene expression by licofelone in OA cartilage.

Published
2005

22. Validity of pain assessment methods in an experimental dog model

Author

Rialland, P., primary, Moreau, M., additional, Pelletier, J.-P., additional, Martel-Pelletier, J., additional, Lajeunesse, D., additional, Boileau, C., additional, Caron, J., additional, del Castillo, J., additional, Beauchamp, G., additional, Gauvin, D., additional, and Troncy, E., additional

Published
2010
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50. Can altered production of interleukin-1β, interleukin-6, transforming growth factor-β and prostaglandin E2by isolated human subchondral osteoblasts identify two subgroups of osteoarthritic patients

Author

Massicotte, F., Lajeunesse, D., Benderdour, M., Pelletier, J.-P., Hilal, G., Duval, N., and Martel-Pelletier, J.

Abstract

ObjectiveTo determine the capacity of human subchondral osteoarthritic osteoblasts (Ob) to produce interleukin (IL)-1β, IL-6, transforming growth factor-β (TGF-β) and prostaglandin E2(PGE2), and determine if a relationship exists between IL-1β, TGF-β, PGE2and IL-6 production.

Published
2002
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