alexa Induction of osteoarthritis in the rat by surgical tear of the meniscus: Inhibition of joint damage by a matrix metalloproteinase inhibitor.


Journal of Arthritis

Author(s): Janusz MJ

Abstract Share this page

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.

This article was published in Osteoarthritis Cartilage and referenced in Journal of Arthritis

Relevant Expert PPTs

Relevant Speaker PPTs

Recommended Conferences

Relevant Topics

Peer Reviewed Journals
Make the best use of Scientific Research and information from our 700 + peer reviewed, Open Access Journals
International Conferences 2017-18
Meet Inspiring Speakers and Experts at our 3000+ Global Annual Meetings

Contact Us

© 2008-2017 OMICS International - Open Access Publisher. Best viewed in Mozilla Firefox | Google Chrome | Above IE 7.0 version