Pathogenesis of Osteoarthritis Flashcards by Lara Everett

what is in the image

synovial joint

bone
fibrous joint capsule
hyaline articular cartilage
synovial membrane (synovium)
synovial fluid

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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

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macrophage like cells

synoviocytes type 1 or type a

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fibroblast like cells

synoviocytes type 2 or b

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label top to bottom

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label top to bottom

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cell and tissue changes as a flow chart

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matrix metalloproteinases

can degrade/ clear aggrecan

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in early OA what occurs in the chondrocytes

proliferate
become more active
form clusters
produce proteinases

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in early OA what occurs in the extracellular matrix

gradual loss of aggrecan
type 2 collagen degradation
cracks in cartilage
termed fibrillation

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what is in the image

early OA

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cartilage changes

decreased swelling pressure of proteoglycans
altered collagen synthesis
decreased responsiveness of chondrocytes
loss of shock absorbing properties

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what is in the image

degradation of cartilage

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what do DAMPs include

endogenous intracellular molecules
released by activated or necrotic cells and ECM

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inflammation in OA

synovitis

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how is synovitis detected

imaging
arthroscopy
histology

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inflammation in OA

chronic
low grade
involves innate immune response

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key components implicated in OA

DAMP-TLR signalling
complement system
CPB
macrophages
mast cells

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cytokines in mediators of inflammation in OA

TNF alpha
Il-1 beta
Il-6
Il-18
Il-21

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chemokine in inflammation mediation

growth factors
adipokines
prostaglandins and leukotrienes
neuropeptides

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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

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grade 2 MCP synovitis

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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