5.1 - Cartilage Biology and Osteoarthritis Flashcards
1
Q
What is osteoarthritis?
A
- disease of the whole joint which involves the loss of articular cartilage
- affects cartilage, soft tissue and bone
- can eventually lead to joint failure
- commonest form of arthritis, numbers rising
2
Q
What is the difference between normal articular cartilage and chondral defect?
A
- normal arthroscopy - you can see the two surfaces of the joints, articular cartilage
- articular cartilage is also known as hyaline cartilage
- smooth, moony white, deforms when probed but bounces back, resilient, tough, designed to take load
- chondral defect - raggedy edge (lose smooth, moony white), pink bone
- can give rise to pain and OA
3
Q
What does normal articular (hyaline) cartilage look like microscopically?
A
- toluidine blue stain - proteoglycans in ECM stained blue
- little spots = articular chondrocytes - the only cell in articular cartilage
- bottom = bone - calcified, tide mark
- bone –> deep/radial zone –> intermediate/transitional zone –> superficial zone
- deep zone: bone-like, chondrocytes are stacking, lot of proteoglycans
- intermediate zone: chondrocytes more widely spaced, more round
- superficial zone: flatter chondrocytes running parallel to articular cartilage surface
4
Q
What does healthy cartilage look like?
A
- proteoglycan (mainly aggrecan) - proteins and mucopolysaccharide chains - combination of protein and carbohydrate
- proteoglycan molecules are big
- they have negative charges = pull water into articular cartilage –> resilient and resists compression
- type II collagen fibrils - architecture and inherent tensile strength
- water molecules pulled in then held as collagen constraining the shape of the cartilage
5
Q
What is the chondrocyte?
A
- only cell in cartilage
- makes up <5% of the tissue
- produces and degrades the articular cartilage matrix arounds its ECM
- highly metabolically active
- exist in relative hypoxia - no blood vessels around
- interactions with ECM - growth factors, receive mechano-transduction signals from matrix
- no cell division after adolescence
6
Q
What is type II collagen and collagenases?
A
- type II collagen is the articular cartilage collagen
- metalloproteinase - MMP-1, MMP-8, MMP-13 are collagenases
- cleavage is 3/4 way along the collagen molecule
- other molecules can also act as collagenases e.g. cathepsin K
7
Q
What is aggrecan and aggrecanases?
A
- protein stems with three globular domains - G1, G2, G3
- side of backbone has mucopolysaccharide chains - chondroitin sulfate and keratin sulfate chains - highly -ve charged = pulls in water and holds it
- lots of these molecules join on to sugar backbone - hyaluronan chain
- two types of enzymes break down aggrecan at specific points:
- matrix metalloproteinases e.g. MMP-3 (a stromelysin)
- aggrecanases e.g. ADAMTS-4&5
8
Q
What are anabolic and anti-catabolic factors for articular cartilage in the joint?
A
- stop the breakdown of cartilage
Intrinsic:
- TIMPs (tissue inhibitor of metalloproteinases) 1-4
- growth factors e.g. fibroblast growth factor (FGF-2), insulin-like growth factor (IGF), transforming growth factor (TGF-B), activin A
Extrinsic:
- hormones e.g. testosterone, oestrogen
- some drugs e.g. FGF-18
9
Q
Why does matrix loss occur?
A
- excessive degradation - too much breakdown from these metalloproteinases
- reduced anabolism/repair
10
Q
How does mechanical load affect cartilage?
A
- cartilage/chondrocytes need mechanical load to maintain cartilage thickness and turnover - without this, there is cartilage atrophy e.g. in stroke patients
- compared to standing, the load going through the tibiofemoral joint of your knee increases:
- walking - 2-6x body weight
- jumping - 7-9x body weight
- running - 3-8x body weight
- climbing stairs - 3-10x body weight
- if you increase your weight by 5kg, your knees will support 15-30kg more pressure on walking
- load is always greater through the medial compartment of the knee
11
Q
What is the pathogenesis of osteoarthritis?
A
- many tissues are affected in the synovial joint in OA:
- articular cartilage
- subchondral bone
- ligament and soft tissue
- inflammation, repair and remodelling, pain pathways are important
12
Q
What are the molecular changes that precede structural changes in OA?
A
- excessive degradation
- proteoglycan is fragmented by aggrecanases
- collagen broken down by collagenases
- water - initial swelling of matrix, then lost
13
Q
What is the pathology of OA?
A
- early OA - loss of proteoglycans in superficial zone of articular cartilage
- there is then fibrillation of surface - loss of articular cartilage integrity, more loss of proteoglycan staining
- established OA - fissuring - loss of integrity going down into the cartilage rather than just superficial
- partial and full thickness loss, osteophytes (new bits of bone emanated that are generated as part of healing attempts), bone cysts, synovial inflammation
14
Q
What are the risk factors for OA development?
A
- age
- obesity - increased mechanical load, systemic inflammation
- mechanical factors e.g. joint injury, malalignment
- family history
- chondrodysplasias (e.g. defects in type II collagen) e.g. Stickler syndrome
- other medical conditions e.g. haemochromatosis
- secondary joint damage due to inflammatory arthropathies e.g. rheumatoid arthritis
- around 100 genetic variants associated with OA risk
15
Q
What is post-traumatic OA?
A
- OA following injury
- a model for understanding early mechanisms in OA
- 50% with meniscal or anterior cruciate ligament tear will develop OA within 5-10 years
- individuals are generally young (30s-40s)
- inflammatory response can be seen in the joint response to joint trauma (e.g. MMP-3, IL-6 in synovial fluid)
