Understanding the Role of Inflammation in Secondary Osteoarthritis

Abstract

Osteoarthritis (OA) is the most seen form of arthritis, affecting a  population of about 3.3 to 3.6% worldwide. In the ranking, it is the 11th most incapacitating disease worldwide, and in about a 43million people, it causes mild to severe disability. Estimated that 80% of the population In the United States over 65 years old have radiographic evidence of OA, although only 60-70% of this subset has symptoms. There were about 1 million hospitalizations for OA in 2011, with a cumulative cost of nearly $15 billion. This makes A the second most expensive disease seen in the United States [1, 2]. Secondary OA can affect older adults, and it could also affect younger people, usually those under 35 years of age. Secondary OA has been regarded more as a mechanically-driven disease than an inflammatory disease. However, low-grade inflammation plays some part in cartilage degeneration and repair at many stages of arthropathy. In the past years, many published scientific papers on both animal models and human studies have indicated an increased role for both synovial inflammations and the activation of the membrane attack complexes of the complement system in the pathogenesis of secondary OA. There is also increasing evidence that significant risk factors for secondary OA have been linked with changes in systemic and local (at the articular cartilage chondrocyte level) cytokines and inflammatory mediators. However, it remains controversial whether or not the inflammatory mediators are primary or secondary regulators of the damage to the cartilage or defective repair mechanisms present in secondary Osteoarthritis because the pathways for signaling involved in inflammatory and biomechanical stress are very much similar. So, these pathways could also induce and increase the expression of cytokine and chemokine genes. Although research on the inflammatory mediators associated with Osteoarthritis has been done and much knowledge has been gained in the last decade, more studies are needed to define better the mechanisms by which these factors tip the balance between homeostasis and activation to promote cell death and matrix destruction. In response to stress and inflammatory insults, osteoarthritis chondrocytes produce a variety of matrix-degrading enzymes, including metalloproteinases and aggrecans. The expression of most of these enzymes of degradation is dysregulated in chondrocytes of patients with Osteoarthritis, and their increased activities and aberrant expression are the main contributors to cartilage degradation during osteoarthritis development and progression [3]. This student project aims to understand the role of inflammation in secondary Osteoarthritis.