Term
What cells express RANK? What are they derived from?
What cells secrete RANKL? What are they derived from? |
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Definition
- osteoclasts - macrophages
- osteoblasts - mesenchymal |
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Term
| Osteoprotegerin: what cell type(s) secrete it and what does it do? |
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Definition
- mostly osteoblasts, also stromal and immune cells
- acts as a decoy receptor for RANKL, blocking it's effect on cells expressing RANK |
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Term
| the ratio between which proteins determines bone loss or bone increase? |
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Definition
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Term
What three things do osteoclasts secrete that effect osteoclasts?
Which stimulate their resorption activity and which inhibit it? |
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Definition
- RANKL (stimulate)
-Osteoportegrin (inhibit)
- M-CSF (stimulate) |
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Term
| Other than bone reabsorption, what is another function of osteoclasts? |
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Definition
| - function as APC's fro T-cells |
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Term
| Osteoblasts are main secretors of RANKL, but other cells express this and can drive osteoclast differentiation/activation. What other cell types express RANKL? |
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Definition
- DC's
- T-cells
- B-cells
- monocytes
- neutrophils |
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Term
| What cytokines stimulate cells to produce RANKL? |
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Definition
| - proinflammatory: Il-6, TNF-α, IL17 |
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Term
| What cytokines will inhbit osteoclast differentation/proliferation? |
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Definition
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Term
What effect will a dominant Th1 response have on osteoclasts?
Through what mechanism? |
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Definition
- pro-osteoclast effect
- through INF-y and its activation of macrophages |
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Term
| What affect will a Th17 response have on osteoclast activity? |
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Definition
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Term
What is lacking in rheumatoid arthritis?
What drives this? |
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Definition
- control of Th17
- DC release of IL23 |
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Term
How do Tregs affect osteoclasts?
What cell markers are important here? |
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Definition
| - because osteoclasts are closely related to APC's, interaction with TReg's expressing CTLA-4 will inhibit interaction between their CD80/B7 and Th1 CD28. |
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Term
| Three mechanisms/cell types that estrogen works on? |
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Definition
- Osteoblasts: increase activity
- Osteoclasts: decrease activity
- T-cell: decrease their RANKL expression |
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Term
| Cell types that make up white adiopse tissue? |
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Definition
1) pre-adipocytes
2) adipocytes
3) stromal/vascular cells
4) macrophages |
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Term
Adipocyte pro-inflammatory cytokines
Adipocyte anti-inflammatory cytokines |
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Definition
Pro-inflammatory:
1) Leptin
2) Visfatin
Anti-Inflammatory:
1) Adiponectin
2) Macrophage inhibitory cytotkine (MAC1)
3) SFRP |
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Term
| Two adiopocyte proinflammatory cytokines and their effects |
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Definition
1) Leptin - stimulate production of IL-6,1 and TNF-α
2) Visfatin - angiogenic |
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Term
| Anti-inflammatory adipocyte cytokines and their function |
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Definition
1) Adiponectin: suppression of TNF-α, antagonist to leptin
2) Macrophage inhibitory cytokine: Stiulates adiponectin production
3) SFRP - antagonizes WAT signaling |
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Term
| Two macrophage derived cytokines associated with WAT? |
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Definition
- Osteopontin: chemotactic for monocytes and macrophages
- Resistin: antagonist of adiponectin and promotes TNF-α and IL-6 production |
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Term
| Two major types of macrophages associated with WAT? |
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Definition
M1 - proinflammatory
M2 - anti-inflammatory |
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Term
What is the dominant macrophage type in healthy adipose tissue?
What type of environment is this?
What adipocytokines are associated with it? |
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Definition
- M2
- anti-inflammatory environment
- Adiponectin, MAC-1, SFRP |
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Term
What cytokines do M2's in a non-obese person upregulate?
What do they downregulate? |
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Definition
-Upregulate: IL4, IL10
- downregulate: NFκB |
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Term
| What does "Stuffing" of adiopoctyes cause? |
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Definition
| - activation of signal pathway that results in pro-inflammatory milieu leading to insulin resistance |
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Term
| most potent monocyte attractant from adipocytes and its receptor? |
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Definition
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Term
| Role of osteopontin in obesity? |
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Definition
| - draws monocytes out of blood vessels and into the adipose tissue. |
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Term
| Obesity and cholesterol/arterial plaque |
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Definition
| - choelesterol crystals in arterial plaque may draw macrophages to the area perpetuating inflammation |
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