Pathogenesis of Osteoarthritis Flashcards
What is the function of articular cartilage?
To cap the ends of the bone at synovial joints to provide a smooth and slippery surface with a very low coefficient of friction
What type of cartilage is articular cartilage?
Hyaline
How does articular cartilage merge with the bone?
The deeper layer of the hyaline cartilage merges with a calcified layer (tidemark) that attaches it to the subchondral bone
What are five the layers of articular cartilage?
Superficial (tangential) zone Middle/intermediate/transitional zone Deep/radial zone Tide mark Calcified zone (BONE)
Describe the chondrocytes in the superficial layer of articular cartilage
Flatter, smaller and in greater density
Describe the chondrocytes in the middle/intermediate layer of articular cartilage
The cells are rounder, larger and sparser
Describe the chondrocytes in the deep layer of articular cartilage
The chondrocytes are stacked as they have proliferated
Why layer of articular cartilage is mainly responsible for the production of proteoglycans?
Deep layer - have prominent ER and golgi apparatus (responsible for protein synthesis and sulphating of mucopolysaccharides which form the proteoglycans)
Describe the composition of the extracellular matrix in cartilage
80% water, type II collagen and proteoglycans (hyaluronic acid core protein with GAG side chains)
Describe the structure of proteoglycans
Consist of a core protein (e.g. hyaluronic acid) with GAG side chains (e.g. keratin sulphate or chondroitin sulphate)
Name an example of a proteoglycan
Aggrecan
How does articular cartilage derive it’s nutrients?
It is avascular, lacking blood and lymphatic vessels, and therefore the survival and synthetic activity of the cartilage depends upon the diffusion of nutrients through the matrix (which is facilitated by the lack of a basement membrane in the synovium)
What surrounds each chondrocyte?
Lacunae (lie in a puddle-like structure)
What is a lacuna?
A pool that surrounds each chondrocyte in cartilage
Why do chondrocytes have a low number of mitochondria?
They aren’t very metabolically active, they only divide in response to injury or disease
Describe the orientation of collagen fibres in the superficial layer of articular cartilage
Collagen lies parallel with the surface of cartilage to allow gliding
Describe the orientation of collagen fibres in the middle layer of articular cartilage
Collagen has a criss-cross, oblique organisation to allow for compression
Describe the orientation of collagen fibres in the deep layer of articular cartilage
Collagen lies perpendicular to the surface
What is the most prominent type of collagen present in articular cartilage?
Type II
Where is type II collagen most dense in articular cartilage?
Superficial layer
Where is type X collagen most dense in articular cartilage?
Calcified deep layer
What types of collagen are present in articular cartilage?
Type II, IX, X and XI
Mainly II, with a little X
What are the risk factors for osteoarthritis?
Intrinsic joint vulnerability, systemic factors and use factors (obesity/injurious physical activity)
Outline the genetic basis that may influence the pathogenesis of osteoarthritis
HMGB2 (high mobility group protein 2) - expressed by chondrocytes in the superficial zone to support chondrocyte survival and differentiation of progenitor cells, therefore loss of this expression/gene leads to superficial zone cell death and loss of progenitor cells –> reduced synthesis of components for the ECM
What gene is associated with the pathogenesis of osteoarthritis?
HMGB2
What are the macroscopic three phases of degeneration in osteoarthritis?
Fibrillation, erosion and cracking and eburnation (complete loss of cartilage)
What are the microscopic changes that occur in osteoarthritis?
Chondrocyte necrosis (more marked in superficial layer with focal clumps of proliferation; form isogenic clusters), there is a change from type II to type I collagen which leads to the formation of a second tidemark (visible on histology) with a thickening of the calcified cartilage (which merges with the subchondral bone)
What are the biochemical changes seen in osteoarthritis?
> Articular cartilage thickens and swells due to increased water uptake
There is loss of proteoglycans
Collagen network begins to be broken down (due to release of MMPs, collagenases and ADAMTs from stressed synovial membrane cells and chondrocytes)
Provide an overview of the pathogenesis of osteoarthritis
Something causes increased expression of degradative enzymes in chondrocytes –> greater breakdown to deposition of cartilage. Gradual change from type II to type I cartilage and there is swelling. Chondrocytes attempt to repair and become ‘stressed’ which leads to the release of MMPs, collagenases and ADAMTs which then breakdown the collagen network –> cartilage breakdown. Eventually the cartilage will fibrillate (crack) and ‘joint mice’ fragments come off, which are engulfed by type A synoviocytes –> inflammatory mediators are attracted –> further degradation –> until there is complete eburnation (Bone on bone).
How may osteoarthritis affect the subchondral bone?
As the articular cartilage is eroded, the underlying bone is exposed which can lead to micro fractures of the trabecular that cause osteoblasts to form new bone –> subchondral stenosis
