Normal and abnormal synoviol joints Flashcards
What lines the surfaces of synovial joints
Articular cartilage
What type of cartilage is found on the articulating surfaces of synovial joints
Hyaline cartilage
What are the 2 main membranes of a joint capsule
Outer fibrous capsule and inner synovial membrane
Function of articular cartilage
Reduces friction and absorb impact/ shock
Where is hyaline cartilage found
Capping the end of bones in synovial joints
What does the deeper layer submerge with
Subchondral bone
What is the tidemark
Calcified layer that the subchondral bone merges with
Upon what structure do the properties of articular cartilage depend upon
Composition of the ECM
What cells are responsible for maintaining and regulating the composition of ECM
Chondrocytes
Name in order from superficial to deep the layers of the articular cartilage
Superficial zone Middle zone Deep zone Tide mark Calcified zone Subchondral zone Cancellous bone
In which direction do chondrocytes move
Surface layer to deep
How do the chondrocytes appear in the superficial zone
Flattish
How do the chondrocytes appear in the deep zone
More rounded
What % of the total volume of cartilage are chondrocytes
<5%
In which layer are chondrocytes stacked
Deep/ radial layer
What do chondrocytes sit in
Lacuna
What staining is used to see hyaline cartilage layers
Safranin-O
What % water is the ECM of cartilage
80
What collagen is found in the ECM of cartilage
Mainly collagen II
What is the function of the collagen found in cartilage (2)
- Network gives overall framework and shape
- Makes pockets filled with proteoglycan complexes
How do proteoglycans interact with water, and why
Draw water into cartilage
Regulates compressibility
What type of collagen is found in the deep cartilage (not II)
X
Describe the structure of collagen in the articular surface of cartilage
Parallel arrangement
Surface highest tensile properties
Allows for gliding
Describe the structure of collagen in the intermediate layer of the cartilage
Criss-crossed oblique allows compression
Describe the structure of collagen in the deep layer of the cartilage
Perp to surface
Name 4 types of collagen found in cartilage
II, IX, X, XI
What % of dry weight is made up by collagen
40-70%
What % of dry weight is made up by proteoglycans
15-40%
What is the structure of a proteoglycan
Core protein with glycosaminoglycan (GAG) side chain
What are GAGs
Linear polysaccharides with repeating units
2 most prevelant GAGs in synovial joint
Keratin sulphate
Chondroitin sulphate
What is the core protein of the proteoglycan found in the synovial joint
Hyaluronan
State the ways in which a osteoarthritic synovial joint differs from a normal health one
- Fibrotic
- Synovitis
- Cartilage failure
- HA depolymerised
- Osteophytes
- Subchondral cysts
- Vascular engorgement
Name 4 extrinsic/ biochemical factors for the development of osteoathritis
High BMI
Physical activity levels
Occupational exposures
Past joint injury
Name 5 genetic links to osteoathritis
- ASTN2
- GDF5
- GLN3
- DOT1L
- 7q22
Name 5 systemic risk factors for the development of osteoathritis
Post- menopausal HRT Bone mineral density Diet Female Increasing age
Describe the genetics behind 7q22
Loss of GPCR 22= 30% increased risk of knee OA
What is DOT1L
Enzyme: master protector of chondrocytes
What is GDF5
Growth differentiation factor 5
What is ASTN2 thought to be involved in
Pain and neuronal adhession
Does synovitis occur primary or secondary to established bone and cartilage pathology
Secondary
What is the effect of synovitis
Drives further inflammatory damage to adjacent bone and cartilage
Major cause of pain and lsos of function
What does HMGB2 stand for
high mobility group protein 2
Where is HMGB2 uniquely expressed
In the superficial zone chondrocytes
What is the role of HMGB2
Supports chondrocyte survival
Regulates specific differentiation status of superficial zone cells
What is the result of HMGB2 loss
Superficial zone cell death
Loss of progenitor cells
Reduced ECM component synthesis
Name the 3 stages articular cartilage goes through macroscopically
Fibrillation
Erosion/ cracking
Eburnation
What happens during eburnation
Complete loss of cartilage
Exposed bone becomes polished
Microscopically, name the 3 changes that occur in osteoathritis
Chondrocyte necrosis
Focal clumps/ clones of chondrocytes
Change to fibrocartilage from hyaline
Where is chondrocyte necrosis most significant
Superficial layers
What happens during the change to fibrocartilage from hyaline
Type 1 instead of 2
Reduced thickness of articular cartilage
Thickening of calcified cartilage merging with subchondral bone
How does movement of the water differ in people with OA as opposed to normal
Early stage: cartilage swells increasing the water.
Loss of proteoglycans mean less compressible so water moves in and out faster
How does collagen network change in OA
Breaks down due to release of enzymes from stressed chondrocytes and synovial membrane cells
What is chondromalacia
Softened cartilage
What does CSPC stand for
Chondrocyte stem/ progenitor cell
What characterises early OA
Loss of superficial zone and changes to ECM of the articular cartilage
Cell clusters emerge
What characterises late OA
Continued loss of ECM and chondrocyte hypertrophy
What happens due to exposure of underlying bone due to cartilage erosion
- Microfractures of trabeculae
- Increased osteoblastic activity
- Surface undergoes focal pressure necrosis
What is the result of focal pressure necrosis
Subarticular cysts
What happens due to vascular engorgement
Slower blood flow and bone marrow oedema
How does osteoathritis appear on an x-ray
Loss of joint space
Subchondral sclerosis
Trabecular fracture
Subchondral cysts
Name the therapeutic targets for OA treatment in the early stages
1) Cartilage stem/ progenitor cells could help regenerate joint resurfacing
2) ECM production and chondroprotection
