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Chondroprotective Activity of a Matrix Metalloprotease Inhibitor, CGS 27023A, in Animal Models of Osteoarthritis

  • Conference paper
Advances in Osteoarthritis

Summary

Breakdown of articular cartilage is a primary feature of osteoarthritis (OA) that leads to loss of joint function. Cartilage degradation involves a progressive loss of proteoglycan matrix and chondrocytes, surface fraying, and erosion. Matrix metalloproteases (MMPs) have been implicated in the destruction of cartilage in OA. CGS 27023A is an orally active inhibitor of stromelysin (MMP-3) and collagenase (MMP-1). CGS 27023A was used to evaluate the effects of an MMP inhibitor on the development of cartilage pathology in a surgical model of OA in rabbits and naturally occurring OA in guinea pigs. Focal OA lesions were produced in rabbits by partial lateral meniscectomy (MNX). Rabbits given CGS 27023A at 100mg/kg in food for 8 weeks following MNX had a lower mean score for cartilage pathology (P <.005) than controls. Spontaneous OA occurs naturally in the knees of guinea pigs, starting during the first 6 months of age and progressing during the next year. By 12 months of age, articular cartilage degeneration including loss of proteoglycan and chondrocytes and surface fibrillation were observed in the medial tibia of the majority of untreated guinea pigs. Guinea pigs administered CGS 27023A in food from 6 months to 12 months of age had reduced histology scores for cartilage lesions (P <.05). These observations support the hypothesis that an MMP inhibitor would ameliorate cartilage destruction by protecting the collagen framework and proteoglycan matrix in OA patients.

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Author information

Authors and Affiliations

  1. Novartis Institute for Biomedical Research, 556 Morris Avenue, Summit, NJ, 07901, USA

    Elizabeth O’Byrne, Vincent Blancuzzi, Hem Singh, Lawrence J. MacPherson & David T. Parker

  2. Tulane Regional Primate Research Center, 18703 Three Rivers Road, Covington, LA, 70433, USA

    E. Donald Roberts

Authors
  1. Elizabeth O’Byrne
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  2. Vincent Blancuzzi
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  3. Hem Singh
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  4. Lawrence J. MacPherson
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  5. David T. Parker
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  6. E. Donald Roberts
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Editor information

Editors and Affiliations

  1. Kinki University School of Medicine, 377-2 Ohno-Higashi, Osaka-Sayama, 589-8511, Osaka, Japan

    Seisuke Tanaka M.D. (Dean) (Dean)

  2. Department of Orthopedic Surgery, Kinki University School of Medicine, 377-2 Ohno-Higashi, Osaka-Sayama, 589-8511, Osaka, Japan

    Chiaki Hamanishi M.D. (Professor) (Professor)

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© 1999 Springer-Verlag Tokyo

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O’Byrne, E., Blancuzzi, V., Singh, H., MacPherson, L.J., Parker, D.T., Roberts, E.D. (1999). Chondroprotective Activity of a Matrix Metalloprotease Inhibitor, CGS 27023A, in Animal Models of Osteoarthritis. In: Tanaka, S., Hamanishi, C. (eds) Advances in Osteoarthritis. Springer, Tokyo. https://doi.org/10.1007/978-4-431-68497-8_13

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  • DOI: https://doi.org/10.1007/978-4-431-68497-8_13

  • Publisher Name: Springer, Tokyo

  • Print ISBN: 978-4-431-68499-2

  • Online ISBN: 978-4-431-68497-8

  • eBook Packages: Springer Book Archive

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