Normal and Abnormal joints the pathogenesis of OA Flashcards
what type of cartilage is the articular cartilage made out of
hyaline cartilage
Name the components of synovial capsule
- articular cartilage
- synovium (synovial membrane)
- fibrous capsule
- ligaments
- synovial fluid within joint cavity
What makes up the articular capsule
- Fibrous capsule and synovial membrane
what does the articular cartilage allow for
- gives a smooth and slippery surface reducing friction between the articulating surfaces
- helps absorb impacts protecting the underlying bone
what does the articular capsule do
- holds the articulating bones together
- it is fibrous
Describe hyaline cartilage
- caps the ends of bones in synovial joints
- smooth, slippery and very low coefficient of friction
- deeper layer merges with subchondral bone via a calcified cartilage layer
What is the properties of the articular cartilage dependent on
- Elastic and resilience
- properties depend on the composition of the extracellular matrix
What maintains and synthesis the extracellular matrix
Chondrocytes
describe the layers of articular cartilage
Superficial zone
- resting reserve cartilage
- small flattened chondrocytes that are parallel
- the reserve cells gradually move into the middle zone
Middle/transitional zone
- chondrocytes become more active
- go back into the cell cycle and are proliferating
- become bigger and more rounded
Deep/radial Zone
- become more rounder
- hypertrophy
- form columns = end up with daughter cells underneath each chondrocytes
calcified
- chondrocytes undergo lysis and die leaving an empty hole
- they die they release cellular contents into the ECM
- become calcified
what does chondrocytes do
Chondrocytes regulate both synthetic and catabolic processes
- they establish a specialised microenvironment and are responsible for ECM around them
How much of the volume do chondrocytes make up
- less than 5% of total volume of cartilage
describe how the shape, size and number of chondrocytes change
Superficial/tangential - flatter, smaller and in greater density
Intermediate/transitional - rounder, larger and sparser - more metabolically active
Deep/radial - stacked up as they have proliferated.
what does chondrocytes sit in
lacuna space
describe characteristics of chondrocytes
- low number of mitochondria as they have a low oxygen consumption
- cell division is low - occurs in response to injury or disease
- deep chondrocytes have prominent endoplasmic reticulum and golgi apparatus
why do deep chondrocytes have prominent endoplasmic reticulum and Golgi apparatus
Responsible for protein synthesis and sulphation of mucopolysaccharrides that form proteoglycan side chains
what makes the ECM of cartilage
chondrocytes
describe the ECM matrix of cartilage
- up to 80% water
- Collagen (mainly type II)
- contains proteoglycans that draw water into the cartilage
- lacks blood and lymphatic vessels
- no nerve supply
what is the role of collagen type II in the ECM of cartilage
Network of fibrils, give overall framework and shape of cartilage
Makes pockets filled with proteoglycan complexes
Collagen fibres - right up edges of lacunae
what is the role of proteoglycans in the ECM of cartilage
- these draw water into cartilage and regulate compressibility
- these are between the gaps in the chondrocytes in the middle zone
how does the ECM get nutrients and metabolites
- Survival and synthetic activity depends on diffusion of nutrients and metabolites through matrix therefore there is more oxygen present in the superficial and middle zone
- Fine balance of anabolism and catabolism
What other collagen is present in the ECM of cartilage
II(Main type), IX, X(present in the deeper zone) and XI
describe the collagen direction in the superficial, intermediate and deep zones of articular cartilage
Superficially - parallel with surface highest tensile properties allows gliding
Intermediate - criss-crossed oblique allows compression – proteoglcyans in the pockets
Deep - perpendicular to surface follow stacks of chondrocytes
descirbe where type II collagen is and what percentage it makes up
Type II collagen 90-95%
- Present in all layers but more in superficial layers
describe type X collagen and where it is
Type X collagen
Higher levels in calcified deeper layers
how much of dry weight is the collagen in the articular cartilage
40-70% of dry weight
- forms a 3D network of fibrils
what do most proteoglycans exist as
aggregates such as aggrecan
How much of dry weight do proteoglycans form in articular cartilage
15-40% of dry weight
describe aggregates of proteoglycans
- core protein
- GAG side chains (glycosaminoglycan)
describe the characteristic of proteoglycans
- has many negative charges
- highly hydrophilic
- trap water forming ground substance
- contributes to shock absorbing properties
what is the core protein in proteoglycans
hyaluronan
define GAGs and name some examples
GAGs linear polysaccharides of repeating disaccharide units
- Keratin sulphate (KS)
- Chondroitin sulphate (CS)
what is the primary tissue that is lost in Oestoarthritis
- the articular cartilage
- everything else is secondary damage after you have lost and damaged the articular cartilage
Describe what happens once the articular cartilage has been damaged in osteoarthritis
- articular cartilage fails and undergoes necrosis and cracking so the underlying bone is exposed
- bone undergoes changes and starts to form an osteophyte
- the osteophyte irritates the synovial membrane causing inflammation within the synovial membrane
- inflammation causes a failure in the production of hydrolyrunic acid
- lowers them viscosity of the synovial fluid
what is an osteophyte
a bony projection associated with the degeneration of cartilage at joints
what increases your risk of osteoarthritis
Extrinic and biomechanics factors
- high BMI
- past joint injury
- physical activity levels
Intrinsic factors
- infection
- past joint surgery
- congenial abnormalities
Systemic factors
- post menopausal hormone replacement therapy
- genetic
- increasing age
- female gender
- diet
- bone mineral density
describe the role of pro inflammatory cytokines in the pathophysiology of osteoarthritis
when chondrocytes become stressed they release pro inflammatory cytokines that lead to an inflammatory response in the rest of the joint
- pro inflammatory cytokines increase the production of matrix proteases reducing the amount of aggrecan and collagen type II that is made
- areas are not replaced with new extracellaurl matrix so you end up with an area of cartilage that is not replaced
- IL-1, 6, 17 and TNF alpha are the inflammatory cytokines that also create local inflammation in the synovium
What are the inflammatory markers that create inflammation int eh synovium
- IL-1, 6, 17 and TNF alpha are the inflammatory cytokines that also create local inflammation in the synovium
what is synovitis secondary to
Synovitis secondary to established bone and cartilage pathology
Once it sets in it drives further inflammatory damage to adjacent bone and cartilage
What is the major cause of pain and loss of function in osteoarthritis
- synovitis caused by pro inflammatory cytokines
what gene is involved in the cause of osteoarthritis
HMGB2
what does HMGB2 stand for
HMGB2 = high mobility group protein 2 (chromatin Protein)
where is HMGB2 expressed and what does it do
HMGB2 uniquely expressed in the superficial zone chondrocytes
- supports chondrocyte survival and regulates the specific differentiation status of superficial zone cells, including progenitor cells
what does loss of HMGB2 lead to
- leads to superficial zone cell death means that there is less reserve cells so fewer chondrocytes that can replace damaged chondrocytes further down
- loss of progenitor cells,
- reduced synthesis of ECM components
what are the three phases of degeneration macroscopically of the articular cartilage
Fibrillation
Erosion and Cracking
Eburnation
describe the three phases of degeneration macroscopically of the articular cartilage
Fibrillation
- it becomes rougher so you get free edges to the surface of the articular cartilage and then it becomes rougher and you start to get these cracks this is fibrillation
Erosion and Cracking
- synovial fluid goes underneath the cracks
- this pushes the cracks further apart and peels the cartilage of the bone
Eburnation
- this is when you lose a bit of cartage completely and it breaks of becoming a loose body in the synovial fluid
what are the microscopic changes of osteoarthritis
- Chondrocyte necrosis in superficial layers
- focal clumsy or clones of chondrocytes due to increased local proliferation
- change to fibrocartilage from hyaline
describe how the hyaline cartilage changes to fibrocartilage in osteoarthritis
- Type 1 collagen rather than type II
- reduces thickness of articular cartilage
- thickening of calcified cartilage merging with subchondral bone
describe biochemically what happens in osteoarthritis
- In early stages of OA the articular cartilage thickens and swells due to increased amount of water
- loss of proteoglycans makes it less compressible
- therefore water moves in and out faster due to the less amounts of proteoglycans
- collagen network breaks down as enzymes are released from stressed chondrocytes and synovial membrane cells
- cartilage softens and progresses to fibrillation
what does chondromalacia stand for
- the means that the cartilage softens and progresses to fibrillation
What enzymes are released from stressed chondrocytes
MMPs, collagenases and ADAMTS
what does CSPC stand for
chondrocyte stem/progenitor cell
what is the difference between early OA and late OA
Early OA
- characterised by loss of superficial zone and changes to the ECM of the articular cartilage and cell clusters emerge
Late stage OA
- characterised by continued loss of ECM and chondrocyte hypertrophy
what happens once the bone is exposed
- micro fractures of trabecular
- increased osteoblastic activity and new bone formation
- surface undergoes focal pressure necrosis - subarticular cysts
- vascular engoregement, slows blood flow and there is bone marrow oedema
What is subchondral sclerosis
Subchondral sclerosis is the hardening of the bone just below the cartilage surface. It shows up in the later stages of osteoarthritis
what are the therapeutic targets in early OA
Cartilage stem/progenitor cells (CSPCs) could help regenerate joint resurfacing,
ECM production and chondroprotection