GELATINASE B (MMP-9) MODULATES JOINT INFLAMMATION AND CARTILAGE DEGRADATION AFTER OVERLOAD INJURY

摘要

Osteoarthritis is the leading cause for disability in the U.S. Primary osteoarthritis occurs progressively with age due to a variety of factors, while secondary osteoarthritis is usually the result of a sports or accident-related joint injury. Several recent studies found that degraded matrix in synovial fluid was surged within days after initial injury along with the elevation of matrix degradative enzymes, including matrix metalloproteinases (MMPs) and aggrecanases [1]. The elevation of degraded matrix could last for up to a decade, although it is not clear whether these degradative events are related to joint inflammation, the chronic presence of which is the hallmark of rheumatoid arthritis and often leads to joint degeneration. Of particular interests is MMP-9, which is also known as gelatinase B. The elevation of MMP-9 is critical for the recruitment of T cells, macrophages, and synovial fibroblasts, which often initiates a cascade of degradative events through several pro-inflammatory cytokines including interleukin 1 (IL-1) and tissue necrosis factor alpha (TNF-α).^sIn addition to its role in mediating cell migration, MMP-9 can also digest aggrecan core protein and denatured collagen (gelatin) after cleavage first by collagenase. Furthermore, MMP-9 was recently found to regulate angiogenesis in growth plate cartilage and to cleave precursor TNF-α at a site slightly different than TNF converting enzyme (TACE or called ADAM-17), effectively interfering with the actions of TNF-α.^sRegarding musculoskeletal system, MMP-9 is also found important for long-bone formation. Using a transgenic knockout technique, Vu et al found an increase of hypertrophic zone in growth plate cartilage and a delayed formation of secondary (epiphyseal) ossification center in MMP-9-deficient mouse at birth [2]. Although no significant differences were noticed at 3 weeks after birth, 10% shorter long bones were found in MMP-9-deficient mouse as compared to the wildtype [2].