L24 - Bone & RA

Question 1

What are the effects of TNF on osteoblasts in vitro?

Answer 1

1) decrease wnt signalling by increasing DKK1 expression
2) decrease RUNX protein levels (no osteoblasts –> no bone formation)
3) decrease alkaline phosphatase (prevents mineralisation)
4) Increase RANKL expression
5) decrease capacity of osteoblast-lineage cells to form properly mineralised bone
6) increase apoptosis

Question 2

What are the effects of TNF on osteoclasts?

Answer 2

Increase RANK expression on osteoclast progenitors

Increase the number of osteoblast progenitors

Question 3

What are the effects of IL1 on osteoclasts and osteoblast?

Answer 3

Osteoclasts
- fusion of cells
- cell survival
Osteoblasts
- Unknown (no clear study to date)

Question 4

What extracellular proteins do osteoblasts produce?

Answer 4

• collagen
• bone sialoprotein
• osteoclastin
• alkaline phosphatase

Question 5

What are the two main factors required for osteoclast differentation?

Answer 5

• RANKL

- M-CSF (macrophage colony-stimulating factor)

Question 6

What are the forms of bone loss in RA?

Answer 6

•juxta-articular/peri-articular osteopenia
The obvious one early on in disease
Occurs within the traceular/cancellous bone in the region adjacent to the affected joint.
There is increased translucency on a radiograph - losing bone density at that site.
•Focal bone erosion:
Occurs early on within cortical bone within the arthritic joint, initially at junction of cartilage and bone
•Systemic osteoporosis
With time, patients will present with systemic osteoporosis. This occurs later in disease and involves the thinning of the trabecullar and the cortical bone at sites remote from affected joints eg hip, vertebrae. These patients are high risk of fractures