Osteoarthritis Flashcards
What does dejenerative joint disease/osteoarthritis generally lead to?
structure failure of a synovial joint
pain and disability
erosion of cartilage
osteophyte formation
joint space narrowing
What structures are involved in osteoarthritis?
cartilage, synovium, bone, enthesis, tendons, ligaments, muscles, neural, vasculature
in late stage: systemic
What drives osteoarthritis?
proinflammatory cytokines
What is the difference between idiopathic and secondary OA?
idiopathic: underlying cause not always known but associated with age, mechanical overuse, genetics
secondary: explained by a known medical condition/cause
What are the 4 zones of hyaline articular cartilage and what is in their ECM?
superficial: horizontal layer on collagen and chondrocytes
mid: aggrecan/hyaluronan/link protein along with collagen and chondrocytes
deep: vertical version of mid
calcified zone: sub-chondral bone
What is the function of cartilage?
dissipation of loads during locomotion
smooth lubrication surface between joints
What are the forces acting on cartilage?
dynamic compression
dynamic shear
static compression
What are the general characteristics of articular cartilage?
chondrocytes: synthesise matrix, reside within lacunae
avascular: no new supply of cells, poor capacity to repair when injured, nutrient supply is via the vascularised subchondral bone and the synovial surface
aneural
ECM: major component in collagen type 2 for resilience and tensile properties, contains proteoglycans = ++ water
load bearing: experiences various types of loads, reversible deformation, dissipates load across a larger area to reduce impact trauma
What are normal age related changes regarding chondrocytes?
depletion in numbers
senescense (stress-induced)
reduced anabolic activity and response to growth factors and cytokines
increased catabolic activity (more responsive to proinflammatory cytokines, increase in matrix metalloproteinases)
mesenchymal stem cells (depletion of local population)
What is the consequence of depleting chrondrocyte numbers?
effect on homeostasis
What is the consequence of chondrocyte senescence?
promote inflammation
What is the consequence of reduced anabolic activity of chondrocytes?
altered homeostasis
What are the consequences for increased catabolic activity of chondrocytes?
altered homeostasis and reduced hydration of the ECM
What is the consequence of depleting numbers of mesenchymal stem cells?
impact on differentiation and replenishing new chondrocytes, effects repair and homeostasis
What are normal age-related changes to ECM?
thinning
mechanical stiffening
accumulation of ECM degradation products
decrease in water component
What are the consequences of ECM thinning?
alters loading biomechanics
What are the consequences of mechanical stiffening of ECM?
increased cross-links between collagen fibers, stiffens the ECM
alters loading biomechanics and fatigue failure
What are the consequences of accumulation of ECM degradation products?
activation of chondrocytes and synovial cells, promote inflammation
What are consequences of decreased water content in ECMS?
increased compressive stiffness
What is the difference between age related changed and OA?
age-related changes appear to mimic those found in OA but they have very distinct processes
What are the risk factors and pathophysiological mechanisms leading to OA?
excess and abnormal mechanical loading
dysregulated cytokine activity
chronic low levels or pro-inflammatory cytokines
absence of systemic manifestations of inflammation
synovium inlammation secondary response to degradation products
synovitis increasingly recognised in early disease
What physiological functions of chondrocytes are important for cartilage remodelling?
- balance between several cytokines to maintain anabolic and catabolic activities of the ECM and modulate the activities of other cytokines
- imbalance between anabolic and catabolic mechanism leads to cartilage loss
What is IL-1 and its role in OA?
major player in OA with TNF-alpha
produced by chondrocytes and synovial macrophages
up-regulates most proteinases in chondrocytes
makes TNF alpha much more potent
What are microscopic changes see in early-stage OA?
cartilage, minor fibrillation in superficial to transition zone
chondrocyte hypertrophy/clustering
subchondral bone mass reduction
synovial thickening and inflammatory cells (lymphocytes) migration
