Pathogenesis of Osteoarthritis Flashcards
what is in the image
synovial joint
bone
fibrous joint capsule
hyaline articular cartilage
synovial membrane (synovium)
synovial fluid
healthy synovium
thin lining facing joint space, 1 to 2 cells thick
contains macrophage like cells called synoviocytes type 1/a and fibroblast like cells synoviocytes type2/b
synovial subliming is loose connective tissue with numerous blood and lymphatic vessels, nerves, scattered macrophages and fibroblasts
macrophage like cells
synoviocytes type 1 or type a
fibroblast like cells
synoviocytes type 2 or b
label top to bottom
label top to bottom
cell and tissue changes as a flow chart
matrix metalloproteinases
can degrade/ clear aggrecan
in early OA what occurs in the chondrocytes
proliferate
become more active
form clusters
produce proteinases
in early OA what occurs in the extracellular matrix
gradual loss of aggrecan
type 2 collagen degradation
cracks in cartilage
termed fibrillation
what is in the image
early OA
cartilage changes
decreased swelling pressure of proteoglycans
altered collagen synthesis
decreased responsiveness of chondrocytes
loss of shock absorbing properties
what is in the image
degradation of cartilage
what do DAMPs include
endogenous intracellular molecules
released by activated or necrotic cells and ECM
inflammation in OA
synovitis
how is synovitis detected
imaging
arthroscopy
histology
inflammation in OA
chronic
low grade
involves innate immune response
key components implicated in OA
DAMP-TLR signalling
complement system
CPB
macrophages
mast cells
cytokines in mediators of inflammation in OA
TNF alpha
Il-1 beta
Il-6
Il-18
Il-21
chemokine in inflammation mediation
growth factors
adipokines
prostaglandins and leukotrienes
neuropeptides
growth factors in inflammation mediation
TGF beta
adipokines in mediating inflammation
leptin
adiponectin
visfatin
resistin
neuropeptides in mediating inflammation
bradykinin
substance P
what is in the image
grade 0 MCP synovitis
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grade 1 MCP synovitis
what is in the image
grade 2 MCP synovitis
what is in the image
grade 3 MCP synovitis
constitutional risk factors
ageing
hereditary
gender
hormonal status
metabolic bone disease e.g. Pagets
local risk factors
trauma
knee: obesity, quads weakness, joint laxity/ malalignment
hip: developmental dysplasia, occupation
what is the most prominent risk factor for OA development
ageing
ageing as a risk factor
reduced muscle mass
increased fat mass
alter joint loading
elevated levels of reatctive oxygen species can cause oxidative damage and disruption of cell signalling
chondrocytes have reduced levels of ECM gene expression
undergo cellular senescence with age
hereditary risk factor
60% hand and hip
40% of knee
inheritance
related to changes in multiple genes
polygenic
hip and knee OA have different genetic aetiologies
hand OA
mutation in aggrecan gene, AGC1
what is in the image
heberdens node
bouchards node
genes associated with hip OA
GDF5
DIO2
SMAD3
GDF5
bone morphogenetic protein
joint development
DIO2
thyroid metabolism
SMAD3
TGF beta signalling
maintenance of articular cartilage
which gender has a greater risk
female
gender as a risk factor
marked incidence of knee OA at menopause
oestrogen declining
chondrocytes have oestrogen receptors
oestrogen deficiency favours OA
HRT improves symptoms
precise mechanism unclear
obesity as risk factor
overweight 2.5 times more likely to develop knee OA
altered biomechanics
subchondral bone
leads to joint degeneration
accelerates OA process
how can exercise weight loss and low fat diet help
clinically beneficial
pain reduction
improved joint function
obesity as risk factor, detail
adipose tissue secretes adipokines and cytokines
can promote low grade inflammation
obese adipose tissue has M1 macrophages, dendritic cells, T and B cells and neutrophils
secrete Il-6, TNF alpha and VEGF
TNF alpha and Il-6 inhibit production of proteoglycans and collagen 2
upreg MMP expresión
leptin in obesity
expression increased
leads to cartilage destruction and increased il6, CXCL8 expression in synovium
resistin in obesity
increased expression
increased MMP release
increased cartilage destruction
synovial inflammation
visfatin in obesity
expression increased
increased MMPs and ADAMTS release from articular chondrocytes
synovial inflammation and bone erosion
adiponetic in obesity
expression in obesity decreased
leads to cartilage destruction and synovial inflammation
previous joint injury
injury caused y compression torsion shear
damaging the ligaments cartilage or muscles
resulting in pain joint Mal-alignment and locking
occupation as risk factor
observed in occupations squatting and kneeling
hip OA with prolonged lifting and standing
hand OA in those with manual dexterity
joint abnormality/morphology
one in 10 hip replacements in adults
one in 3 in people under 60
