S3: Cartilage and Chondrocyte - What goes wrong with articular cartilage?

Question 1

Describe x ray of joint in large joint osteoarthritis

Answer 1

• OA patient has lost most their joint space (cartilage is normally in this space). This leaves underlying bone on bone.
• There are often thickened bone changes (thickened trabeculations in response to damage of cartilage) . Osteophytes are also seen - these are little bits of bone that grow outwards and these are a useful sign of osteoarthritis in a joint.

Question 2

What are the stages of cartilage breakdown during arthiritis?

Answer 2

• Normal cartilage which has lots of chondrocytes and lots of matrix.
• Early fibrillation where chondrocytes die and there is loss of matrix. The chondrocytes are the only cells making the proteins and proteoglycans needed for the formation of cartilage.
• Deep fissuring which is unrepairable.

Question 3

Which proteinases degrade joint tissue?

Answer 3

• The first enzymes to do this are called aggrecanases. The other enzymes MMP (matrix metalaproteinases) break down the collagen and they carry on breaking the tissue down. This is a positive feedback loop on breaking down cartilage and it is very difficult to halt in its path.
• Clinical trails of MMP and aggrecanase inhibitors have ben shown to be effective in rodents but they had lots of side effects in humans (muscle aches, tendinitis which are symptoms that we are trying to prevent in arthritis!).

Question 4

What structures are affected in OA?

Answer 4

• OA is a condition of the whole joint not the cartilage.

- There are changes that target specific areas in the joint that include cartilage and bone.

Question 5

What are the inflammatory changes in OA to tissue?

Answer 5

• Lining cell hyperplasia.
• Increased vascularity.
• Mononuclear cell perivascular aggregates.
• Subintimal fibrosis.

Question 6

Describe NICE guidelines and treatment for OA

Answer 6

1. Weight loss is the first step of treatment - adherence is the main challenge. Strengthening excersizes and aerobic fitness training.
2. Pharmalogical intervention - topical/oral NSAIDs

Question 7

What is the osteochondral junction?

Answer 7

Osteochondral junction is the space between cartilage and bone.

Question 8

Describe what happens to the osteochondral junction in OA

Answer 8

• In patients with OA, there is a lot of change at the osteochondral junction. There are new blood vessels being formed and expression of nervous system molecules e,g. Nerve growth factor and angiogenesis markers.
• In patients of RA, there are lots of inflammatory infaltrate B cells, T cells, macrophages all releasing cytokines, TNF-a. TNF -a is good at being blocked by methotrexate.

Question 9

Describe autologous chondrocyte implantation for chondral defects

Answer 9

• Criteria for treatment: the person has not had previous surgery to repair articular cartilage defects
• There is minimal osteoarthritic damage to the knee (as assessed by clinicians) - mild and moderate (not severe) OA.
• The cartilage defect is over 2 cm2 and the procedure is done at a tertiary referral centre.
• Alternative treatment is chondral defect repair with microfracture.
• Graft of collagen base membrane and cells.