1a cartilage biology and osteoarthritis Flashcards
what is osteoarthritis?
a disease that affects the whole joint which involves the loss of articular cartilage
what is the most common form of arthritis?
osteoarthritis
what is the most common reason for hip/knee replacement surgery?
pain caused by osteoarthritis
describe the macroscopic features of articular cartilage?
smooth, spoony white
what is the other name for articular cartilage?
hyaline
describe the layers/structure of articular cartilage?
superficial
transitional/intermediate
deep/radial
what 3 things does the ECM of cartilage contain?
- proteoglcyans - mainly aggrecan
- type 2 collagen
- water
what is the most common type of proteoglycan found in articular cartilage?
aggrecan
How does aggrecan pull water in/ exterior swelling pressure?
it has negative side chains which draws water in
what is the function of type 2 collagen in cartilage?
it provides tensile strength + gives architecture
what is the only cell type found in articular cartilage?
chondrocyte
how can chondrocytes function at hypoxia?
cartilage is avascular tissue, so has no blood supply anyways, so has adapted to survive with little O2
what is true about cell division of chondrocytes?
they undergo no cell division after adolescence
why is it problematic that chondrocytes do not undergo cell division post adolescence?
bc if injure your articular cartilage, your body is not good at healing it.
your body heals it with fibre cartilage which doesn’t have same functional properties of articular cartilage
what are collagenases?
enzymes that breakdown collagen
what are major specific collagenases?
- MMP 1,8 + 13
- MMP 3
what does MMP mean?
metalloprotienase
what is the other name of MMP 3?
stromelysin
what is an example of a non-specific collagenase?
Cathepsin-K
what are aggrecanases?
enzymes that degrade aggrecan
what are the two main types of aggrecanases?
- MMP
- aggrecanases such ADAMTS ( 4 +5)
describe the structure of aggrecan
looks like toilet brush
what can inhibit aggrecanases? (4)
intrinsic such as:
1. TIMPS (tissue inhibitor of metalloproteinases)
2. growth factors e.g IGF
extrinsic such as:
1.hormones
2. some drugs
what causes ECM loss?
excess enzymatic degradation of aggrecan and type 2 collagen. thought to lead to OA
how does cartilage maintain its thickness?
via mechanical load such as walking/ standing.
hence, lack of physical activity can lead to atrophy of cartilage
how does an increase in weight affect the mechanical load on your knees?
it causes a 3 fold increase in the pressure exerted on your knees. this is why being overweight is a key risk factor for OA
what 4 parts of the joint are affected by OA?
- articular cartilage
- subchondral bone
- ligament and soft tissue
- synovium
explain the pathophysiology of OA?
1.get excess enzymatic degradation of type 2 collagen and aggrecan via aggrecanases and MMPs
2. proteoglycans are now fragemented
3. overall, causes water loss and integrity of articular cartilage is lost :(
what is likely to be seen in the staining of joint in early OA?
loss of proteoglycan staining in superficial zone
fibrillation in superficial zone
what is likely to be seen in the staining of joint in established OA?
loss of proteoglycan + fissuring in both superficial and intermediate zones of cartilage
what are the key risk factors for OA developement?
age, obesity, joint injury, family history
what’s one of the biggest risk factors for OA?
ligament tears attained from injuries significantly increase likelihood of getting OA
Is OA more common in men or women/
women
what are the 3 places in body where OA is most common?
knees, hands + hip
why is the prevalence of OA increasing?
As we have an ageing population and increased levels of obesity
how do you diagnose OA?
- joint pain during activity
- stiffness typically <30 mins
- loss of function
- examihnation findings: creptius, bony deformity
what feature is commonly associated with hand OA?
heberden’s nodes (bony overgrowths found in finger joints)
what are the 3 main ways of managing OA as per the NICE guidelines?
- increase exercise
- weight management
- providing correct information (e.g how its not inevitable and is not always progressive)
What are the surgical options for OA?
total joint replacement. v effective surgery (arthroplasty)
reduces pain significantly