BoneFat Flashcards
How do OB, OC and immune cells communicate?
RANK_RANKL system
What do OB release that promote OC survival and proliferation?
M-CSF
RANK is expressed on pre-OC and OC, what is the cytokine?
RANKL
What is a decoy receptor mainly from OB?
OPG
What ratio determines bone formation?
OPG and RANKL
-any condition that promotes OC dominance will be associated with bone pathology
Can lots of different things make RANKL? What can RANKL be expressed by?
yes
innate and adaptive immune cells, including neutrophils, monocytes, CD, T and B cells
What induces RANKL and promote OC?
Proinflammatory cytokines
1,6,8 TNF
17***
Dominant Th1 response in and around bone associated with INF-gamma and activated macrophages –>pro-clastogenic and bone resorption
Th17 POTENT OC activator
-Th1 or Th2 would inhibit 17—good thing
What inhibits RANKL?
Anti-inflmmatory cytokines like 4 and 10 inhibit OC
-sex hormones
What cytokine is high in bone remodeling in Rheumatoid arthritis? What does this lead to?
IL 23
–>Th 17 cells infiltrate the synovium
IL 17 activates neighboring OC and they proliferate
—>neutrophils
-RANK/RANKL/OPG balance is pro bone loss and causes bony erosions and loss of joint function
What does estrogen promote? What happen in the post menopausal state?
Promotes normal OB and OC function
Post menopausal state: OPG/RANKL balance is altered
- high levels of RANKL causes not increase in OC activity
- blocking RANKL with monoclonal antibody can lead to decreased bone loss
What is the largest endocrine organ?
adipose tissue
-any stimulus that increases inflammation in adipose tissue is a bad thing
What are the functions of white adipose tissue? WAT
- super endocrine organ and critical for homeostasis
- produces hormones, chemokines, and cytokines
- regulates energy storage and expenditure, body mass and immune responses
- composed of pre-adipocytes, adipocytes, stromal/vascular cells and macrophages
What are the two major types of WAT macrophages?
M1=proinflammatory
M2=anti-inflammatory
What are the macrophage cytokines in WAT?
osteopontin-pro-inflamamtory and potent chemotactic signal for monocytes and macrophages
Restin-antagonist of adiponectin( adiponectin is anti-inflamitory)
-Il 1,6,8 TNF alpha
What are the adipocytokines? What do they do?
- Leptin-proinflammatory cytokine
- Adiponectin-anti-inflammatory
- Macrophage inhibitory cytokine-is TNF-like but promotes adiponectin release
- Visfatin-pro-inflammatory and pro angiogenic
WHat is the normal WAT relationship between inflammatory and anti-inflammatory adipocytokines ?
slightly anti-inflammatory milieu
What happens in obese WAT?
expanding fat in adipocytes triggers signals that make WAT very pro-inflammatory
- recruits large number of monocytes and macrophages
- portal vein carries the problem into the liver also into atheromatous plaques
Adipose tissue is also around organs such as the heart what does this mean/
-inflammatory milieu has an effect
What happens to the macrophages in obesity?
Being converted to M1 producing inflammatory cytokines and recruiting more monocytes that are then also converted to pro-inflammatory
What is local obesity?
Fatty artery
- cholesterol in the plaque attract M1 macrophages
- Macrophages secrete CCL2 to attract monocytes and then prohibit them from exiting
- Big plaque to ruptured plaque is clinical problem of huge dimensions –> myocardial infarction
What is CCL2?
chemokine
-brings monocyte in and prevent them from leaving
How are innate immune response held inactive in the brain?
supression by microglia and IL10 and TNF B
WHat are the 2 subsets of microglia in the CNS?
- Act like M2 macrophages, highly branched, display little MHC, don’t want any innate response
- secrete IL 10 and TGF B - Perivascular-derived from circulating monocytes can sense what’s going on in the blood
- can cause a lot of problems
What happens when you get encephalitis?
glial system is activated by DAMPs and PAMPS (perivascular part)
- rapidly converts M2 to M1
- now you have pro-inflammatory macrophages in the brain, - unregulated MHC and change in morphology
- start producing 1,6,8 tnf alpha
- 1,6= depression (even with just a flu)
