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Host Defense Exam 2 > Bone and Fat > Flashcards

Bone and Fat Flashcards

1
Q

Where do osteoclasts and osteoblasts originate from?

A
  • HSCs => preosteoClasts => osteoClasts

- mesenchymal stem cells => preosteoBlasts => osteoBlasts => osteocytes

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2
Q

What else originates from mesenchymal stem cells?

A
  • adipose

- chondrocytes (cartilage)

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3
Q

Describe the effects of Wnt on osteoclast/osteoblast differentiation.

A
  1. promotes differentiation of mesenchymals => preosteoblast
    - inhibits other differentiation pathways (i.e. chondrocytes)
  2. promotes differentiation of mesenchymals => mature osteoblasts
    - inhibited BY TNFa => DKK1
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4
Q

How do osteoblasts affect osteoclast differentiation?

A
  1. expression of RANKL => bind to RANK on premature osteoclasts => mature osteoclasts
  2. mature osteoblasts secrete OPG => sequesters RANKL => inhibits differentiation of osteoclasts
  3. M-CSF promotes OC survival
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5
Q

What are RANK/RANKL?

A
  • part of TNFa superfamily
  • regulates formation of multinucleated osteoclasts
  • maintains osteoclasts population for bone remodeling
  • RANK is expressed on pre-OC and OC
  • RANKL is secreted by OB
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6
Q

Define OPG.

A

OsteoProteGerin

  • binds to RANKL
  • inhibits osteoclast differentiation
  • protective in premenopausal women
  • made by OB
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7
Q

What is an important determinant of bone mass and skeletal integrity?

A

RANKL/OPG balance

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8
Q

Define M-CSF.

A

Macrophage Colony Stimulating Factor

  • released by OB
  • promotes OC survival and maturation
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9
Q

Describe the effects of PTH on bone resorption.

A
  1. low calcium levels stimulate PTH release from parathyroid
  2. PTH binds to osteoblasts
  3. osteoblasts secrete RANKL and M-CSF
  4. promotes osteoclast maturation
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10
Q

Which immune cells express RANKL?

A
  • neutrophils
  • monocytes
  • DC
  • T and B lymphocytes
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11
Q

What is the effect of proinflammatory cytokines on bone?

A

IL-1, IL-6, IL-8, TNFa, IL-17
- induce RANKL
- promote OC maturation
==> bone resorption

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12
Q

What is the effect of anti-inflammatory cytokines on bone?

A

IL-4, IL-10
- inhibit OC maturation
==> protect bone

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13
Q

What is the effect of sex hormones on bone?

A

estrogen stimulates OPG

  • OPG inhibits RANKL and OC maturation
  • prevent over-resorptions
  • protects and maintains bone integrity
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14
Q

Why is maintaining a Th1/Th2 response balance important for bone integrity?

A
  • Th1 inflammatory response via IFNg and macrophages causes OC maturation and bone resorption
  • Th17 is also a potent OC activator
  • having a balanced Th1/Th2 response will inhibit Th17 => prevent too much bone resorption
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15
Q

Describe the mechanism of Rheumatoid Arthritis.

A
  • high levels of IL-23 in the synovium
  • recruits Th17 cells to the joint
  • IL-17 activates OC maturation
  • RANK/RANKL/OPG balance favors bone loss => bone erosion => loss of joint function
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16
Q

Describe the mechanism of Osteoporosis.

A
  • low levels of estrogen => low OPG => high levels of RANKL => promotes OC maturation
17
Q

What is a potential treatment for bone cell imbalance related disorders?

A

Denosumab

  • inhibits RANKL
  • restores balance
18
Q

Define White Adipose Tissue (WAT).

A
  • endocrine organ critical for homeostasis
  • produces hormones, chemokines, cytokines
  • regulates energy storage/expenditure, body mass, immune response
  • composition: pre-adipocytes, adipocytes, stromal cells, macrophages
19
Q

Describe the types of macrophages.

A 
M1 = pro-inflammatory
M2 = anti-inflammatory
20
Q

Define osteopontin.

A
  • made by macrophages in adipose
  • pro-inflammatory
  • recruits monocytes and macrophages to adipose tissue
21
Q

Define resistin.

A
  • made by macrophages in adipose
  • inhibits adiponectin (makes insulin)
  • promotes insulin resistance
22
Q

Define leptin.

A
  • adipocytokine
  • controls satiety
  • pro-inflammatory
23
Q

Define adiponectin.

A
  • adipocytokine
  • makes insulin
  • anti-inflammatory
24
Q

Define macrophage inhibitory factor.

A
  • adipocytokine
  • behaves like TNFa
  • promotes adiponectin
25
Q

Define visfatin.

A
  • adipocytokine
  • pro-inflammatory
  • pro-angiogenic
26
Q

Describe the composition of non-obese WAT.

A
  • balanced pro- and anti-inflammatory adipocytokines
  • slightly anti-inflammatory
  • macrophages regulate adipogenesis by Wnt and SFRP5
27
Q

Describe the composition of obese WAT.

A
  • decreased pro-inflammatory adipocytokines
  • lots of fat = lots of osteopontin = recruits more and more macrophages (LOTS)
  • portal vein carries fat to liver and creates atherosclerotic plaques => stroke
28
Q

Define SFRP5.

A

Secreted Frizzle-like Receptor Protein

  • binds to Wnt from macrophages
  • increased in obesity and metabolic disorder
29
Q

Describe how macrophages are involved in plaque formation.

A
  • cholesterol recruits M1 macrophages
  • macrophages secrete CCL2 to attract more monocytes
  • buildup of plaque can lead to rupture and stroke
30
Q

Describe the immune state of the brain.

A

suppressed via microglia, IL-10 and TGF-b

- T cells are able to cross BBB

31
Q

What are the 2 types of microglia?

A

M2-like

  • migrate early in development
  • highly branched
  • show little MHC

M1-like

  • perivascular
  • derived from circulating monocytes
32
Q

Define astrocytes.

A

maintain BBB

33
Q

Define oligodendrocytes.

A

maintain myelin sheath of CNS

34
Q

Describe activation of the glial system.

A
  1. antigen activates DAMP/PAMP
  2. M2 microglia converted to M1 microglia (upregulation of MHC and change morphology)
  3. secretion of pro-inflammatory cytokines (IFNg, IL-17, TNFa)
  4. activation of endothelial cells and astrocytes
  5. stimulate NFkB inflammatory cascade
  6. IL-6 maintains positive feedback loop
  7. neurotransmitters inhibit inflammatory response to maintain balance
35
Q

What are the effects of IL-6 and inflammation on the brain?

A

delirium

long term brain injury

Host Defense Exam 2 (11 decks)

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