Osteoarthritis Flashcards
Define osteoarthritis
degenerative joint disease occurring primarily in elderly characterized by erosion of articular cartilage, hypertrophy of bone at margins (osteophytes), subchondral sclerosis
What are risk factors for developing OA?
age, joint location, obesity, genetic predisposition, joint malalignment, trauma, gender
What are the early morphologic changes in early OA?
1) articular cartilage surface irregularity;
2) superficial clefts w/in tissue
3) altered proteoglycan distribution
What are the late morph changes in late OA?
1) deepened clefts,
2) increase in surface irregularities;
3) articular cartilage ulceration (exposes underlying bone)
How do osteophytes form?
chondrocytes form clusters or clones in attempt at self repair then marginal osteophytes can form
What family of proteases degrades the joint?
MMPs degrade proteoglycans (aggrecanases) and collagen (collagenases)
What causes secondary OA?
suboptimal repair response of normal articular cartilage to injury
What are the mediators of OA?
IL-1B;
TNF
What is the relationship of Nitric oxide and OA?
major catabolic factor produced by chondrocytes in response to pro-inflammatory cytokines
Expression of what factor is increased in OA chondrocytes?
inducible cyclooxygenase-2
How is cartilage affected in early OA?
cartilage surface becomes roughened and irregular and superficial clefts within tissue become apparent
Where are osteophytes typically found?
peripheral margins of joints at interface between cartilage and the periosteum
What is a cartilage contributing factor to the initiation and progression of OA?
reduction in cell number observed in aging cartilage and reduced synthetic capability of hypocellular cartilage
In early OA, what are the morph changes in cartilage?
water content increases causing swelling and alteration of mechanical properties
In later OA, what are the morph changes?
type I collagen concentration w/in ECM increases and proteoglycan concentration falls to 50% or less than normal
What is the first irreversible step in OA? why?
degradation of collagen bc it reduces mechanical properties of cartilage
What is the most important step/factor in OA?
MMP-13 => degrades type II collagen and expression is increased in OA
What degrades aggrecan in OA?
MMP and ADAMTS-4
Oxidative injury caused by inflam cytokines, IL-1B and TNFa in OA increase what?
premature chondrocyte senescence
What is a mechanoreceptor on chondrocytes that can sense and respond to mechanical stimuli?
alpha-5-Beta-1
What is responsible for the pain and restriction of joint movement in OA?
osteophytes
Early OA causes sclerosis of subchondral bone via what mechanism?
increased remodeling and hardening of subchondral bone
