Abstract
There is a critical need to understand the mechanisms that govern structural progression in osteoarthritis. While epidemiological studies have largely identified obesity and joint injury as the dominant factors that contribute to osteoarthritis, recent findings suggest that cellular, molecular and biomechanical factors are responsible for the progression of osteoarthritis. At the tissue level, osteoarthritis involves progressive cartilage degeneration, synovial inflammation, disruption of the extracellular matrix and subchondral bone remodelling. The key pathogenic processes include chondrocyte apoptosis, aberrant autophagy, cellular senescence and functional dysregulation, together with synovial hyperplasia and fibrosis. Genomic studies and Mendelian randomization have identified genetic loci that contribute to osteoarthritis susceptibility and might explain some of the observed heterogeneity in disease phenotypes and progression. Given that there are presently no standard therapies or guidelines to arrest structural progression in osteoarthritis, there is an immediate need to categorize robust biomarkers for initial detection of osteoarthritis and develop rehabilitations that target primary pathogenic pathways. To accomplish this, it is important to integrate epidemiological, genetic and mechanistic data to define osteoarthritis phenotypes, stratifying risk, with the ultimate objective of translating fundamental insights into effective prevention and treatment strategies. The present overview aims to address this aspect of osteoarthritis.