6 - Normal and Abnormal Joints, Pathogenesis of OA Flashcards
What is the anatomy of a synovial joint
Synovial membrane then fibrous capsule which surround synovial fluid
Function of synovial fluid
Provides hydration and nutrition to the joint
Allows fricitonless movement
What is the articular cartilage and why is it there
Hyaline cartilage which attaches to the end of a bone to reduce friction and absorb impacts
What makes the articular cartilage
Chondrocytes
The role of articular cartilage
Elastic
Resilient
Acts as a shock absorber
What does the ECM of the articular cartilage consist of
Collagen
Proteoglycans
What are the characteristics of chondrocytes in the superficial/tangential zone
Flattened
Smaller
Greater in density
What are the characteristics of chondrocytes in the Intermediate/transitional zone
Rounder
Larger
Sparser
What are the characteristics of chondrocytes in the Deep/Radial zone
Stacked in columns
Most rounded
What is the function of chondrocytes
Regulate and establish micro-environment (the ECM)
In which layer is there prominent endoplasmic reticulum and golgi apparatus? why?
Deep layer
For protein synthesis and sulphation of mucopolysaccharrides that form proteoglycan side chains
What colour stain are proteoglycans and what is their charge
Red
Negative charge
attract water
What is the ECM of the articular cartilage made up of
80% water Collagen Type 2 mainly Proteoglycans Lack of blood + lymph No nerve supply
What does the collagenT2 do in articular cartilage?
Makes pockets filed with proteoglycans
What is the function of proteoglycans
Draw water into the cartilage
Regulates compressibility
Water comes out when you move
What is the orientation of collagen fibres superficially?
Parallel with the surface
gives highest tensile properties
Allows gliding
What is the orientation of collagen fibres intermediately?
Criss-crossed oblique allows compression
What is the orientation of collagen fibres Deep?
Perpendicular to surface follow stacks of chondrocytes
What is the main collagen type in the cartilage?
Collagen type 2 (90-95%)
Mainly in superficial layers
Where is collagen type 10 found in the cartilage?
Calcified, deeper layers
Other types of collagen in the cartilage?
2,9, 10, 11
Function of collagen in the cartilage
To hold proteoglycans in place
What percentage of dry weight is collagen and proteoglycans
Collagen = 40-70% PG = 15-40%
Features of proteoglycans
Highly hydrophillic
Negatively charged
Traps water
What is a proteoglycan made up of
Core protein
Glycosaminoglycan side chains
What is the core protein in a proteoglycan
Hyaluronan
What are GAGs and some examples?
Linear polysaccharides of repeating disaccharide units
- Keratin Sulphate (KS)
- Chondroitin Sulphate (CS)
Risk factors for Osteoarthritis
Increasing age Genetics Diet Infection High BMI Physical activity levels
What causes the pain and loss of function in osteoarthritis
Damage to chondrocytes
Causes proinflammatory cytokines to be released from chondrocytes
What is the function of HMGB2
High Mobility Group Protein 2
- regulates DNA of chondrocytes wrapping around histones
Where is HMGB2 expressed and what does it do there
Superficial zone chondrocytes
Supports chondrocyte survival
regulates specific differentiation status of superficial zone cells (inc progenitor cells)
What does loss of HMGB2 cause
Loss of progenitor cells
Death of superfical zone
reduced synthesis of ECM components
3 Phases of degeneration the articular cartilage goes through in osteoarthritis
1) Fibrillation - small cracks on the surface
2) Erosion and cracking
3) Eburnation - complete loss of cartilage, exposed bone becomes polished
Microscopic pathology of osteoarthritis
Chondrocyte necrosis
Clumps of chondrocytes rather than columns
Change from hyaline to fibrocartilage (Type 1 not 2), reduced thickness
What occurs biochemically to the cartilage
Collagen broken down
Cartilage thickens and swells
Loss of proteoglycans so less compressable
Why can there be subchondral sclerosis in osteoarthritis
Bone tries to make itself harder to deal with the lack of articular cartilage
Also subarticular cysts
Treatment for early osteoarthritis
Cartilage stem/progenitor cells (CSPCs) could help regenerate joint resurfacing,
o ECM production and chondroprotection
