Biochemical Role of Matrix Metalloproteinase -9 in Rheumatoid Arthritis

Rheumatoid arthritis (RA) is a systemic autoimmune pathology associated with a chronic inflammatory process, which can damage both joints and extra-articular organs, including the heart, kidney, lung, digestive system, eye, skin and nervous system.(Cojocaru et al. 2010, Conforti et al. 2021). Rheumatoid arthritis affects most commonly the hand, wrist, and foot, but it can also affect large joints .IT is characterized by painful, swollen joints that can severely impair physical function and quality of life and associated with increased mortality (Sparks et al. 2016). About 70% of patients with RA are women, and peak incidence is between ages 50 and 60 years (Sparks et al. 2019). Matrix Metalloproteinases are a family of calcium-dependent endopeptidases with a zinc-binding active side. More than 20 different MMPs are classified according to the particular substrates they degrade: collagenases, stromelysins, gelatinases, matrilysins, membrane-type MMPs, and others. Moreover, MMPs release growth factors from carrier proteins, inactivate proteinase inhibitors, and influence inflammatory cytokines and chemokines that can also be responsible for joint destruction(Nagase et al. 2006) . In the human body, MMPs are synthesized in leukocytes, macrophages, endothelial cells, and connective tissue cells such as chondrocytes and synoviocytes, both found in the knee joint. Matrix metalloproteinases are secreted as pre-proenzymes into the extracellular fluid, where they can be activated by a variety of substances: epidermal growth factor (EGF), vascular endothelial growth factor (VEGF), tumor necrosis factor-α (TNF-α), interleukin-1 (IL-1), and other MMPs. Conversely, steroid hormones, transforming growth factor-β (TGF-β), plasma proteins such as a2-macroglobulin and a1-antitrypsin, and tissue inhibitors of metalloproteinases (TIMPs) can inhibit MMP activity(Visse and Nagase 2003). The pathogenesis of RA is based on the fact that the patient's body reacts to autoantigens, e.g.