Lecture 28 - Bone in RA

Question 1

What are the patterns of bone loss in RA? (3 types)

Answer 1

Juzta-articular/peri-articular osteopenia = trabecular bone near joint

Focal bone erosion - cortical bone at the junction of cartilage and bone

systemic osteophorosis - thinning of cortical and trabecular

Question 2

which cells also produce RANKL in RA?

Answer 2

Synovial Fibroblasts

Tcells

B cells - a little

Question 3

RANKL expression “outweighs” ____ expression at the pannus-bone interface in RA

Answer 3

OPG - pro-osteoclastic environment

Question 4

What is the bone phenotype of mice that have no functional RANKL

Answer 4

Osteopetrotic - no fucntion osteoclasts and think, dense bone

Question 5

compared to their wild type littermates what happens to bone when RA is induced in RANKL KO mice?

Answer 5

No bone errosion but still inflammation

Question 6

OPG injection treatment lead to?

Answer 6

decrease number of osteoclasts within the inflammed joints

Decreased bone erosion

Decreased systemic bone loss

Question 7

Osteoblast ________ and bone formation is impaired in RA at the interface of imflammation and bone

Answer 7

Osteoblast maturation and bone formation is impaired in RA at the interface of imflammation and bone

Question 8

What inhibits osteoblast maturation and function in RA

Answer 8

Expression of multiple antagonists of Wnt signalling is increased in inflammatory arthritis

i.e More DKK-1 in serum (by TNF)

Question 9

What happens to bone in TNF.Tg mouse model (overexpresses TNF and develops RA spontaneously) of RA when DKK-1 action is inhibited?

Answer 9

Protection from bone loss due to active bone formation AND reduced osteoclasts

Question 10

Blocking DKK-1 activity -

protection from bone erosion via…

Answer 10

increase in OPG inhibtion of osteoclasts), increase in bone formation and osteophyte formation

Question 11

Direct effect on osteoclasts is mediated by which cytokines in RA?

Answer 11

IL-1, TNF and RANKL

Question 12

Indirect effect on osteoclasts is mediated by which cytokines in RA?

Answer 12

TNF, IL-1, IL6

Question 13

TNF and IL-1 directly augment ______ differentiation

Answer 13

TNF and IL-1 directly augment osteoclast differentiation

promotes cell fusion

Question 14

RUNX2 is one of the key transcirption factors required for ______ ________

downregualted by

Answer 14

osteoblast diferentiation

downregualted by TNF

Question 15

alkaline phosphatase and osteocalcin gene expression are expressed when

downregulated by.

Answer 15

later stages osteoblast differentiation

downregualted by TNF

Question 16

__decreases the capacity of osteoblast-linage cells to form properly mineralised bone

Answer 16

TNF

Question 17

repair of bone erosion is associated with

Answer 17

minimal inflammation

Question 18

Why may bone not be repairing even in remission patients?

Answer 18

Smoldering synovitis - detected by MRI in clinically “normal” joints

Question 19

Healing of erosion is more common in patients with ____ _______

Answer 19

TNF inhibitor

Question 20

What are some things to target inflammation?

Answer 20

Anti-TNF

anti IL-6