β£Definition of osteoarthritis?Progressive loss of articular cartilage and subchondral bone remodelingβ£What is the pathogenesis of OA?Initiating event is fatigue wear of articular cartilageLeads to disrupted proteoglycan, collagen meshwork β increased porosity and water contentWith increased water β stiffness decreases, Young's modulus reducesSecondary damage to chondrocytes leads to release of cell enzymes (Matrix Metalloproteinases) that further break down matrixMeanwhile, compensatory increase in chondrocytes attempts repairβ£Causes?PrimarySecondary - Post-traumatic, gout, AVNβ£Macroscopic Changes?Softening, fibrillation, pitting, erosion, delamination, denudationβ£Microscopic changes? What components?3 components to examine - Matrix, Cells, and EnzymesMATRIXProteoglycans - reduction leads to loss of compression strengthCollagen network - reduction leads to loss of tensile strengthWater content - increases due to increased porosity of weakened collagen networkCell - CHONDROCYTES - become more active to compensateEnzymes - Matrix Metalloproteinase (MMP) - activity increases when activated by inflammatory cytokinesβ£What are key differences from normal aging?Differences in terms of pathogenesis:Collagen and proteoglycan content - decreased in OA, leading to reduced stiffnessWater content - increased in OAStiffness/Young's modulus - decreased in OAChondrocytes - increased in OA as compensatory responseAging hasreduced water contentmaintained collagen and proteoglycan (so stiffness and Young's modulus increase)reduced chondrocyte countincrease in AGEs (advanced glycation end-products) that enhance collagen cross-linking β increased stiffness β increased brittleness β greater susceptibility to fatigue failureβ£What is the key distinguishing factor between OA and aging?OA has increased IL-1 and MMPβ£What are AGEs?Advanced glycation end-productsNaturally occur during agingResult from uncontrolled, non-enzymatic glycation and oxidation between proteins and sugarsAccumulate with age, making tissue stiffer but more brittleLead to increased fatigue failure β delamination β osteoarthritisβ£What is the pathogenesis of rheumatoid arthritis?Immune-mediated inflammatory response in joints leads to enzyme releaseDevelopment of synovitis and pannus formationDestruction of hyaline cartilage and periarticular soft tissue attenuationJoint instability and abnormal mechanics lead to secondary osteoarthritisπHow long will you lie there,Β O sluggard? When will you arise from your sleep? Proverbs 6:9