Document Detail


The effects of tenidap on canine experimental osteoarthritis: II. Study of the expression of collagenase-1 and interleukin 1beta by in situ hybridization.
MedLine Citation:
PMID:  9598897     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
OBJECTIVE: To examine the effect of tenidap on the expression of collagenase- and interleukin 1beta (IL-1beta) genes in experimental canine osteoarthritis (OA). METHODS: The anterior cruciate ligaments of the right stifle joints of experimental dogs were sectioned by a stab wound incision and tissues samples were taken. Four dogs had received no treatment, 4 were treated with oral omeprazole (20 mg/day), and another 4 were treated with tenidap (3 mg/kg/bid) and omeprazole (20 mg/day). The dogs received medication for 8 weeks; all dogs were sacrificed at the end of this period. Tissues from 4 healthy dogs were used as controls. IL-1beta and collagenase-1 gene expression were measured in synovial membrane (synovial lining cells and mononuclear cell infiltrate) and collagenase-1 expression in cartilage using in situ hybridization techniques. Results were calculated as the percentage of cells expressing the gene, and expressed as cell score. RESULTS: The collagenase-1 cell score in the full thickness samples was significantly higher in OA cartilage than in normal cartilage, both in condyles and plateaus (p < 0.0002). Tenidap treated dogs showed a significantly lower cell score in femoral condyles and tibial plateaus in the superficial (p < 0.0002), deep (p < 0.005, p < 0.002, respectively), and full thickness (p < 0.0002) layers compared to OA dogs. No staining for collagenase-1 was observed in normal membrane. In OA synovial membrane, the collagenase-1 cell score was high in both the synovial lining cells and mononuclear cell infiltrate. Tenidap treated dogs showed a significantly lower score compared to OA tissue in both the synovial lining cells (p < 0.03) and the mononuclear cell infiltrate (p < 0.03). The relative decrease in the collagenase-1 cell score in the tenidap treated dogs was more pronounced in the mononuclear cell infiltrate. Staining for IL-1beta was observed in only a few lining cells in normal synovial membrane from unoperated dogs. In OA synovial membrane from untreated dogs, staining for IL-1beta was intense and was found in all dog specimens. The cell score was significantly higher in OA lining cells (p < 0.03) and mononuclear cell infiltrate (p < 0.03) compared to normal. In tenidap treated dogs, the score for IL-1beta was significantly lower than in OA, both in synovial lining cells (p < 0.03) and mononuclear cell infiltrate (p < 0.03). CONCLUSION: Tenidap significantly reduced in vivo expression of collagenase-1 and IL-1beta in experimental OA. These data are an extension of our previous study and showed that tenidap exerts its protective effects on OA lesions, likely by reducing the catabolic pathways of the disease.
Authors:
J C Fernandes; J Martel-Pelletier; D Jovanovic; G Tardif; J A DiBattista; V Lascau-Coman; I G Otterness; J P Pelletier
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  The Journal of rheumatology     Volume:  25     ISSN:  0315-162X     ISO Abbreviation:  J. Rheumatol.     Publication Date:  1998 May 
Date Detail:
Created Date:  1998-07-16     Completed Date:  1998-07-16     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  7501984     Medline TA:  J Rheumatol     Country:  CANADA    
Other Details:
Languages:  eng     Pagination:  951-8     Citation Subset:  IM    
Affiliation:
Université de Montréal, Unité de recherche en arthrose, Centre de recherche L-C. Simard, Centre hospitalier de l'Université de Montréal, Campus Notre-Dame, Québec, Canada.
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MeSH Terms
Descriptor/Qualifier:
Animals
Anti-Inflammatory Agents, Non-Steroidal / pharmacology*
Collagenases / metabolism*
Dogs
In Situ Hybridization
Indoles / pharmacology*
Interleukin-1 / metabolism*
Matrix Metalloproteinase 1
Osteoarthritis / drug therapy*,  metabolism,  pathology
Synovial Membrane / drug effects,  metabolism
Chemical
Reg. No./Substance:
0/Anti-Inflammatory Agents, Non-Steroidal; 0/Indoles; 0/Interleukin-1; 120210-48-2/tenidap; EC 3.4.24.-/Collagenases; EC 3.4.24.7/Matrix Metalloproteinase 1

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