Matrix Metalloproteinases and Their Clinical Applications... : Clinical Orthopaedics and Related Research® (original) (raw)

SECTION II: ORIGINAL ARTICLES: Research

Bramono, Diah S BS*; Richmond, John C MD†; Weitzel, Paul P MD‡; Kaplan, David L PHD*; Altman, Gregory H PHD*

From the *Department of Biomedical Engineering, Tufts University, Medford, MA; †Department of Orthopaedic Surgery, New England Baptist Hospital, Boston, MA; and the ‡Department of Orthopaedics, New England Medical Center, Boston, MA.

Received: September 8, 2003

Accepted: June 4, 2004

One or more of the authors have received funding from NIH (R01 AR46563-01).

Each author certifies that he or she has no commercial associations (e.g., consultancies, stock ownership, equity interest, patent/licensing arrangements, etc.) that might pose a conflict of interest in connection with the submitted article.

Correspondence to: Gregory H. Altman, PhD, Department of Biomedical Engineering, Tufts University, 4 Colby Street, Room 153, Medford, MA 02155. Phone: 617-627-4604; Fax: 617-627-3231; E-mail: [email protected].

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Abstract

Imbalance in the expression of matrix metalloproteinases and their inhibitors contribute considerably to abnormal connective tissue degradation prevalent in various orthopaedic joint diseases such as rheumatoid arthritis and osteoarthritis. Matrix metalloproteinase expression has been detected in ligament, tendon, and cartilage tissues in the joint. They are known to contribute to the development, remodeling, and maintenance of healthy tissue through their ability to cleave a wide range of extracellular matrix substrates. Their role has been extended to cell growth, migration, differentiation, and apoptosis. In orthopaedics, their clinical applications constantly are being explored. The multiple steps in matrix metalloproteinase regulation offer potential targets for inhibition, useful in drug therapy. The correlation between matrix metalloproteinases and progression in joint erosion presents potential prognostic and diagnostic tools in rheumatoid arthritis. Matrix metalloproteinases also can be incorporated into scaffold design to control the degradation rate of engineered tissue constructs. This current review aims to summarize and emphasize the importance of matrix metalloproteinases and their natural inhibitors in the maturation of musculoskeletal tissue through matrix remodeling and, therefore, in the generation of a new clinical potential in orthopaedics.

© 2004 Lippincott Williams & Wilkins, Inc.