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Applied Biochem > Osteoclasts, Osteoporosis, And Fracture Healing > Flashcards

Osteoclasts, Osteoporosis, And Fracture Healing Flashcards

1
Q

What is the origin and lineage of osteoclasts?

A

Hematopoietic origin - macrophage/monocyte lineage

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2
Q

In bone remodeling this is a process by which mature/damaged bone is removed by osteoclasts and replaced with new bone- There is no…

A

Net gain

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3
Q

The process by which bone shape/size is changed by independent actions of osteoblasts and osteoblasts (adding new bone without prior resorption or removing bone without replacing it).

A

Bone modeling

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4
Q

Bone modeling can occur in response to:

A

Longitudinal growth & increase mechanical loading of the bone

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5
Q

Bone modeling can lead to:

A

Net gain or loss of bone

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6
Q

Disease of impaired osteoclast function that leads to bones that are abnormally dense but brittle and prone to fracture

A

Osteopetrosis

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7
Q

Osteopetrosis leads to bones that are abnormally:

A

Dense but brittle and prone to fracture

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8
Q

Osteopetrosis is caused by mutations in genes important for:

A

Osteoclast resorption

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9
Q

A disease of low bone mass that occurs due to the inability of bone formation to keep up with bone resorption

A

Osteoporosis

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10
Q

Osteoporosis is usually seen in:

A

Post-menopausal women and old people

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11
Q

A drug that inhibits bone resorption:

A

Anti-resorptive agent

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12
Q

A drug that stimulates bone formation:

A

Anabolic agent

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13
Q

A fancy word for bone that is dead and does not have any viable osteocytes:

A

Osteonecrotic bone

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14
Q

A complication of bone fracture in which the bone does not heal:

A

Non-union

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15
Q

A disorganized network of cartilage/woven bone formed between the ends of the broken bone and extending beyond the original contour of the bone

A

Fracture Callus

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16
Q

In a fracture callus, the callus is ultimately replaced by ____ following ____.

A

Lamellar bone; remodeling

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17
Q

Fancy word for blood clot

A

Hematoma

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18
Q

A tissue containing newly formed vascular tissue and fibrous ECM usually formed in healing wounds

A

Granulation tissue

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19
Q

A cell that is present in teh wall of capillaries and has mesenchymal stem cell properties since it can differentiate into other cell types such as muscle, fibroblasts, and osteoblasts

A

Pericytes

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20
Q

Pericytes can differentiate into:

A

Muscle, fibroblasts, and osteoblasts

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21
Q

Small cells found in the mature muscle that have stem cell-like properties and provide a source of pretentious for formation of muscle cells, especially in situations of muscle injury/repair

A

Muscle satellite cell

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22
Q

Muscle satellite cells may be able to differentiate into:

A

Osteoblasts

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23
Q

The ability to form cartilage:

A

Chondrogenic

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24
Q

The ability to form bone:

A

Osteogenic

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25
Q

The formation of new blood vessels from the outgrowth of pre-existing vessels

A

Angiogenesis

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26
Q

When new look vessels form de novo

A

Vasculogenesis

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27
Q

A superfamily of structurally and evolutionarily related proteins that include the transforming growth factor betas (TGFBs), the bone morphogenic proteins (BMPs), activists, inhibits and growth and differentiation factors (GDFs)

A

Transforming Growth Factor Beta Superfamily

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28
Q

Transforming Growth Factor Beta Superfamily are structurally and evolutionarily related proteins that include: (4)

A
  1. TGFBs
  2. BMPs
  3. Activins/Inhibins
  4. Growth/Differentiation factors
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29
Q

Osteoclasts express ____ for removing _____

A

Proteases for removing ECM proteins

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30
Q

Osteoclasts express proteins that act as ____ to generate _____ (to reduce pH to dissolve mineral)

A

Proton pumps; H+ ions

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31
Q

Active osteoclasts have specialized _______ to increase the surface area in the resorption compartment

A

Ruffled border

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32
Q

Lifespan of osteoclasts:

A

Short (days)

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33
Q

Osteoclasts are bone resorting cells responsible for:

  1. Bone resorption during ____ & ____
  2. Removal of ____ during tooth eruption
  3. Resorption of _____ of ____ teeth
  4. Removal of ___ during ____ movement
  5. Bone loss in ____
A
  1. Normal bone growth and remodeling
  2. Alveolar bone
  3. Tooth roots; primary teeth
  4. Alveolar bone; orthodontic tooth
    5.Pathological conditions
34
Q

Must occur to maintain bone shape

A

Modeling

35
Q

Osteoclasts originally come from:

A

Hematopoietic Stem Cell (HSC)

36
Q

During osteoclasts differentiation, the hematopoietic stem cell (HSC) will differentiate into:

A

CFU-M

37
Q

During osteoclast differentiation:

HSC —-> CFU-M—> _____

A

Monocyte

38
Q

During osteoclast differentiation:

HSC —-> CFU-M—> Monocyte —->

A

Mononucleated Osteoclasts (perfusion)

39
Q

During osteoclast differentiation:

HSC —-> CFU-M—> Monocyte —-> Mononucleated osteoclast (perfusion) —-> _____

A

Multinucleated osteoclast

40
Q

During osteoclast differentiation:

HSC —-> CFU-M—> Monocyte —-> Mononucleated osteoclast (perfusion) —-> Mutlinucleated osteoclasts ——> ____

A

Resorting osteoclast

41
Q

What is the master transcription factor of osteoclast formation:

A

NFATc1

42
Q

Osteoclast marker genes are associated with the function of the cell which include:

A
  1. Fusion
  2. Adherence to the bone surface
  3. Acid production
  4. Protease production
43
Q

Which transcription factors are downstream of NFATc1?

A

C-fox & NFKB

44
Q

There are two factors produced by osteoblasts/osteocytes that are essential for:

A

OCL differentiation

45
Q

The two factors produced by osteoblasts/osteocytes that are essential for OCL differentiation include:

A
  1. RANKL
  2. M-CSF (aka CSF-1)
46
Q

RANKL is a receptor activator of:

A

NFkB Ligand

47
Q

M-CSF (aka CSF-a) is a ______ stimulating factor.

A

Macrophage colony

48
Q

Promotes proliferation/survival of osteoclast precursors:

A

M-CSF

49
Q

Member of the TNF superfamily that is required for osteoclast fusion and differentiation:

A

RANKL

50
Q

Mater transcription factor that control osteoclasts differentiation:

A

NFATC1

51
Q

Natural inhibitor of RANKL- a decoy receptor:

A

OPG (osteoprotogerin)

52
Q

These osteoclast marker proteins fall under what category:
1. NFATc1
2. C-fos
3. NFkB

A

Transcription factors

53
Q

These osteoclast marker proteins fall under what category:

Tartrate resistant acid phosphatase (TRAP)

A

Enzyme

54
Q

These osteoclast marker proteins fall under what category:

  1. RANK
  2. C-fms
  3. Calcitonin
  4. Integrin alpha-V-beta-3
A

Receptors

55
Q

1.Receptor for RANKL
2.Receptor for M-CSF

A

RANK
C-fms

56
Q

These osteoclast marker proteins fall under what category:

Carbonic a hydrate II & Vacuolar-type ATPase

A

Generates protons/proton pump

57
Q

These osteoclast marker proteins fall under what category:

Cathepsin K and MMP9, and MMP13

A

Proteases

58
Q

Osteoclasts attach via ____ to form sealed zones

A

alpha-V-beta 3 integrins

59
Q

In the mature resorbing osteoclasts, carbonic anhydrase II (CAII) functions to:

A

Generate protons

60
Q

Vacuolated type H+ ATPase pumps protons into _____ which creates acid to ____.

A

Resorption lacuna; dissolve mineral

61
Q

Exchangers on base lateral surface to remove excess bicarbonate

A

Cl- and HCO3-

62
Q

In the mature resorbing osteoclast, _____ maintains the charge neutrality:

A

Chloride channel

63
Q

______ is released into the resorption lacunae to digest matrix proteins:

A

Cathepsin

64
Q

Impaired osteoclast function leads to:

A

Osteopetrosis

65
Q

Osteopetrosis can be due to the failure in osteoclast ____ or osteoclasts form normally but have impaired ____

A

Formation; resorptive function

66
Q

The two major clinical forms of Osteopetrosis:

A
  1. Autosomal dominant
  2. Autosomal recessive
67
Q

Describe the autosomal dominant form of Osteopetrosis:

A

Adult benign type with relatively few symptoms

68
Q

Describe the autosomal recessive form of Osteopetrosis:

A

Infantile malignant type, typically fatal if untreated in early childhood

69
Q

In patients with Osteopetrosis, their bones are:

A

Abnormally dense; prone to fracture

70
Q

Failed osteoclastic resorption affects: (3)

A
  1. Bone growth
  2. Remodeling
  3. Tooth eruption
71
Q

Osteopetrosis can be accompanied by: (8)

A
  1. Scoliosis
  2. nerve compression in head/face (hearing loss, blindness)
  3. Impaired marrow function (anemia)
  4. Enlarged liver or spleen
  5. Dental abnormalities
  6. Short stature
  7. Slow growth
  8. Recurrent infection
72
Q

In Osteopetrosis there are more than 60 mutation identified in gene TCIRG1: encoding the ____ subunit of the vacuoular ____

This accounts for about 50% of ______ Osteopetrosis in humans

A

Alpha3; H+ ATPase

73
Q

A mutation that accounts for 75% of AD forms of Osteopetrosis in humans are caused by mutations in the gene ClC7 which is associated with the:

A

Chloride channel

74
Q

Pycnodysostosis is a specific form of Osteopetrosis caused by mutation in the:

A

Cathepsin K

75
Q

What are the 3 genes that if mutated result in a form of osteopetrosis?

A
  1. TGIRG1
  2. CLCN7
  3. Cathespin K
76
Q

The TCIRG1 gene that gives rise to osteopetrosis (AR) is associated with:

The CLCN7 gene that give rise to Osteopetrosis (AD) is associated with:

A
  1. Vacuolar ATPase alpha3 subunit
  2. Chloride channel
77
Q

What factors can contribute to osteoporosis? (3)

A

Aging population, diet, and environmental factors

78
Q

Osteoporosis is defined by a patient with a BMD ____ standard deviations below average for a healthy young person

A

2.5

79
Q

Worldwide 1 in ____ women and 1 in ____ men over the age of 50 willl experience osteoporotic fractures

A

1 in 3 and 1 in 5

80
Q

Hip fractures associated with osteoporosis are associated with mortality rates of up to ____ in the first year after fracture and a greater risk of dying may persist for at least ____.

A

20-24%

5 years

81
Q

Osteoporosis treatments can be directed at reducing ______, stimulating ______ or both.

A

Reducing bone resorption, stimulating bone formation, or both

82
Q

Treatments for osteoporosis:

Preferentially bind to hydroxyappetite. Inhibit osteoclast activity, by inhibiting the mevalonate pathway important for prenylation of GTPases

A

Amino bisphosphonates

Applied Biochem (18 decks)

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