Biochemical and Cellular Mechanisms in Joint Disease

Question 1

What is osteoarthritis?

Answer 1

Progressive and paermanent deterioration of articulat cartilage

Question 2

What are the 4 risk factors for OA?

Answer 2

Obesity/Metabolism
Genetics
Ageing
Mechanical/Trauma

Question 3

What is the initial biochemical change that occurs in OA?

Answer 3

Cartilage appears to have a loss in the tissue content of proteoglycans, which occurs while the collegen content remains normal however proteogylcan synthesis is increased??!

Question 4

What causes normal cartilage to go to OA cartilage?

Answer 4

Homeostatic imbalance- imbalance between biosynthetic and catabolic activity
Coupled with poor capacity for repair- no vascular/supply of regenerative cells restricted
Cellular phenotype shift
Cell Death

Question 5

What is age relatedchange that occurs in proteogylcans?

Answer 5

Catabolic fragmentation of aggrecan and link protein

Question 6

What are the changes that occur in normal cartilage with age?

Answer 6

Thickenss decreases
Degradation products of prteogylcans increases

Question 7

How can we detect early signs of OA?

Answer 7

Biomarkers- biochemical markers of cartilage and bone metabolism
Synovial fluid, Serum, Urine
COMP
Aggrecan epitope-864

Question 8

What are some of the key changes in cartilage with ageing?

Answer 8

Composition of proteogylcan in matrix compartment changes
modification of GAGs from mostly C4S to C6S
>VULNERABILITY TO DEGRADATION INCREASED

Anabolic responses altered
Response to anabolic cartilage growth factors decline with ageing
>LESS ABLE TO REPAIR

Question 9

Give the 4 points in Biochemical Theory

Answer 9

> Enzyme activation—> Loss of prteogylcans—> Reduced stiffness of cartilage—> Mechanical disruption of cartilage

Question 10

Give the 4 points in Biomechanical Theory

Answer 10

Overuse of cartilage—> Fatigue failure and tissue disruption—> Change in mechanical environment—> Increased cartilage wear and degradation