Cartilage and OA Flashcards
What is osteoarthritis?
Loss of articular cartilage at a joint —> bones rub
What is articular cartilage?
Hyaline cartilage surrounding the ends of bones
What are the 5 layers of articular cartilage?
- Superficial
- Transitional/intermediate
- Deep/radial
- Tide mark —> separates cartilage and bone
(becomes calcified)
What are the 3 components of articular cartilage?
- Proteoglycan (aggrecan)
- Type II Collagen
- Water
What are chondrocytes?
Producer and degrader of cartilage matrix
- only cells found in cartilage (<5% cartilage tissue)
- highly active —> always in hypoxia
- stop dividing after adolescence —> no more bone
growth (just there for repair)
What are MMPs?
Metalloproteinases —> enzymes that breakdown matrix molecules
What is the structure of type II collagen?
Triple helix of 3 α strands
Which enzymes breakdown collagen? (2)
MMPs
- 1, 3 (stromelysin), 8, 13
- collagenases - specific
- non-specific (cathepsin K)
What is the structure of aggrecan?
- Hyaluronan backbone
- Branches of keratin or chondroitin sulfate
Which enzymes breakdown aggrecan? (2)
- MMPs
- Aggrecanases - ADAMTS-4 & 5
- cut near where branch meets
hyaluronan —> lose most of branch
—> aggrecan loses function
Which 4 non-enzymatic factors contribute to articular cartilage production/breakdown?
Intrinsic
1. TIMPs = Tissue Inhibitor of Metalloproteinases
- 1, 2, 3, 4
2. Growth factors - FGF-2, IGF, TGF-β, activin A
Extrinsic
3. Hormones - testosterone (deficicency —> atrophy)
- oestrogen (women OA)
4. Drugs
Which 4 tissues are involved in OA development?
- Articular cartilage
- Synovium
- Subchondral bone
- Surrounding ligaments and soft tissue
What happens to articular cartilage in OA? (3)
Degrades:
1. Proteoglycans fragmented by aggrecanases
2. Collagen broken down by collagenases
3. Water loss (initially swelling)
What are the 3 main symptoms of OA?
- Pain
- Inflammation
- Repair remodelling —> shape changes
What can be seen in scans of joints with OA?
- Cartilage loss —> thinner/none
- Fibrillation —> bits breaking off
- Loss of proteoglycan
- Fissuring
- Synovial inflammation
- Bone —> osteophytes, cysts
What are the risk factors for OA? (9)
- Age
- Obesity
- Female
- Family history
- Mechanical factors (injury, malalignment)
- Chondrodysplasias = collage II defects
- eg. Stickler Syndrome - Co-morbidities - eg. haemochromatosis
- Inflammatory arthropathies —> secondary damage
- Genetics
How can trauma lead to OA in later life?
Joint injury —> inflammatory response to trauma (see MMP-3 and IL-6 in synovial fluid) —> develops into OA over years
- commonly —> meniscal tear
—> cruciate ligament tear
What is the process of developing OA? (5)
- Normal joint with abnormal load
Abnormal joint with normal load - Mechanical tissue injury
- Tissue damage
- Inadequate repair
- Repeated cycle of 2-5
How is OA diagnosed?
- Clinically
- Pain with activity
- Stiffness (<30 mins)
- Loss of function
- Examination —> crepitus (crackling noise)
—> bony deformity
—> joint line tenderness
—> loss of range (movement)
—> warmth
—> effusion (swollen)
Not necessary:
2. X-rays —> staging, treatment planning, progress
3. Blood test —> not rheumatoid arthritis
—> secondary causes (iron, calcium,
PTH, glucose)
Which joints are most commonly affected by OA?
- Knee (more common in women)
- Hand - distal interphalangeal —> Heberden’s nodes
proximal interphalangeal —> Bouchard’s
base of thumb
- menopause —> settle 2-5 years later
How is OA managed?
- Lifestyle - exercise
- weight management
- suppport (life activities) - Drugs
- Surgery - arthroplasty —> full joint replacement
- knee —> uni-compartmental replacement
- thumb base —> trapeziectomy
Which 2 types of drugs for OA are being developed?
- SyMOAD = symptom modifying
—> treat pain + improve function - DMOAD = disease modifying
—> slow progression/prevent OA
