Pathogenesis Of OA Flashcards
What type of cartilage is articulate cartilage
Hyaline
What provides articulate cartilage with nutrients and hydration
Synovial fluid
What merges the deeper layer of articulate cartilage with sub chi drawl bone
Calcified cartilage layer
Tidemark
What decides the properties of articulate cartilage
ECM composition
Layers of articulate cartilage
Superficial zone
Middle zone
Deep zone
Calcified zone
Subchondral zone
Cancellous bone
What layers of articulate cartilage are made up of dead chondrocytes
Calcified and subchondral zones
What triggers calcification of chondrocytes at the tide mark of articulate cartilage
pH change
How does chondrocyte size, shape, and number vary between the superficial, middle, and deep zones of articulate cartilage
Superficial - flatter, smaller, greater density
Middle - rounder, larger, sparser
Deep - stacked
What are chondrocytes found in
Lacunae
Why do chondrocytes have low numbers of mitochondria
Low oxygen consumption
Why do deep chondrocytes have prominent endoplasmic reticulum and Golgi apparatus
Protein synthesis
Sulphation of mucopolysaccharides
What is the main type of collagen in cartilage ECM
Type II
What cells make cartilage ECM
Chondroblasts
Structure of cartilage ECM
Network of collagen fibrils with pockets containing proteoglycan complexes and chondrocytes
Why does cartilage rely on diffusion of nutrients and metabolites
No blood or lymphatic vessels (or nerves)
Main 4 types of collagen in cartilage
II IX X XI
Is collagen X more common in superficial or deep cartilage
Deep calcified
How does collagen fibre orientation differ between superficial, intermediate, and deep cartilage
Superficial - parallel with surface - highest strength + allows gliding
Intermediate - oblique lattice - allows compression
Deep - perpendicular to surface - follows chondrocyte stacks and protect from compression
What is the main proteoglycan in cartilage
Aggrecan
Components of aggrecan
Core protein
GAG side chains
What molecule type are keratin sulphate and chondroitin sulphate
GAG
What do aggrecan complexes bind to
Central hylauronic acid filament
Features of osteoarthritic joint
Fibrosis
Synovitis
Cartilage failure
Hylauronic acid depolymerised
Osteophytes
Subchondral cysts
Vascular engorgement
OA risk genes
GDF5
FRZB
DIO2
COL2A1
Vit D receptor
Oestrogen receptor
IL-1R1
PTGS2/PLA2G4A
OA pathophysiology
Chondrocytes damaged -> emergency signal release -> inflammation -> further damage to cartilage, bone, etc
Inflammation of the synovial membrane
Synovitis
How does Synovitis affect OA
Further inflammatory damage
Pain
Loss of function
How does loss of HMGB2 increase OA
Causes superficial zone cell death, loss of progenitor cells, reduced ECM component synthesis
HMGB2 role
Wraps around histones in chondrocytes to protect from damage
Supports chondrocyte survival
Regulates differentiation of superficial zone cells
Where is HMGB2 expressed
Superficial zone chondrocytes
3 phases of articulate cartilage degeneration in OA
Fibrillation
Erosion and cracking
Eburnation
Eburnation
Exposed bone becomes polished
Microscopic changes in cartilage in OA
Chondrocyte necrosis
Isogenic clusters - Focal clumps of chondrocytes from incr proliferation
Change from hyaline to fibro - C2 becomes C1
Duplicated tide mark
Thinner art cart
Thickened calcified cart
How does proteoglycan staining appear in OA
Patchy
How does increased local proliferation of chondrocytes in OA affect chondrocyte arrangement
Isogenic clusters instead of stacks
Chondromalacia
Cartilage softens
What causes chondromalacia in OA
Art cart thickens and swells but loss of proteoglycans make it less compressible -> water moves in and out faster-> enzymes released from stressed chondrocytes and synovial membrane cells (MMPs ADAMTs collagenases MAC) -> collagen network breaks down
What does chondromalacia progress to
Fibrillation
Main characteristic changes to art cart in early OA
Loss of superficial zone
Changes to ECM
Cell cluster emerge
Main characteristics of art cart in late stage OA
Continued ECM loss
Chondrocyte hypertrophy
Effects of OA on exposed Subchondral bone
Micro fractures
Increased osteoblast activity
Subchondral sclerosis
Focal pressure necrosis
Subarticular cycts
Vascular engorgement
Bone marrow oedema
What causes subarticular cycts
Increased osteoclast activity to repair focal pressure necrosis
What causes Subchondral sclerosis
Increased osteoblast activity
Is damage to Subchondral bone equal over the bone surface
No
