Induction of osteoarthritis in the rat by surgical tear of the meniscus: Inhibition of joint damage by a matrix metalloproteinase inhibitor
| Autor: | A.M. Bendele, Michael J. Janusz, Kimberly K. Brown, Lily C. Hsieh, Sandra A. Heitmeyer, Y.O. Taiwo |
|---|---|
| Rok vydání: | 2002 |
| Předmět: |
Male
Pathology medicine.medical_specialty Matrix metalloproteinase inhibitor Biomedical Engineering Osteoarthritis Matrix metalloproteinase Meniscus (anatomy) Matrix Metalloproteinase Inhibitors Menisci Tibial Lesion Rheumatology Medicine Potency Animals Orthopedics and Sports Medicine Medial collateral ligament business.industry Matrix metalloproteinase inhibitor Meniscal tear model of OA Rats Histology Collateral Ligaments musculoskeletal system medicine.disease Hindlimb Rats Disease Models Animal Microscopy Electron medicine.anatomical_structure Rats Inbred Lew Joints medicine.symptom business |
| Zdroj: | Osteoarthritis and cartilage. 10(10) |
| ISSN: | 1063-4584 |
| Popis: | Objective Characterize a model of osteoarthritis (OA) induced by a surgically transecting the medial collateral ligament and meniscus. Evaluate the effectiveness of a matrix metalloproteinase (MMP) inhibitor in this model. Methods The medial collateral ligament of the right knee of rats was transected and a single full thickness cut was made through meniscus. Rats were sacrificed at various times after the surgery to assess the severity of gross cartilage damage using an image analyser and microscopically by histology. The effect of an MMP inhibitor in this model was assessed by administering compound twice daily for the 21 days and evaluating gross and histological joint damage at day 21. The in vitro potency of the MMP inhibitor (MMPI) against a panel of human recombinant MMPs was assessed kinetically using a quenched fluorescent substrate. Results Surgical transection of the medial collateral ligament and meniscus resulted in a time dependent increase in the severity of the cartilage lesion (depth) as measured histologically but only a slight increase in the area of the lesion as assessed grossly by image analysis. Administration of a MMPI orally twice daily (b.i.d.) at 25mg/kg to rats in the meniscal tear model resulted in significant inhibition of cartilage degradation and osteophyte formation (total joint score) of 39±7% (mean±S.E.M., from four separate experiments). Conclusion These results demonstrate that MMP inhibition is effective in reducing the joint damage that occurs in the meniscal tear model of OA and support a potential therapeutic role for MMP inhibition in the treatment of human OA. Copyright 2002 OsteoArthritis Research Society International. Published by Elsevier Science Ltd. All rights reserved . |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full Text from ScienceDirect