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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
The formation of new blood vessels from the outgrowth of pre-existing vessels
Angiogenesis
26
When new look vessels form de novo
Vasculogenesis
27
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)
Transforming Growth Factor Beta Superfamily
28
Transforming Growth Factor Beta Superfamily are structurally and evolutionarily related proteins that include: (4)
1. TGFBs 2. BMPs 3. Activins/Inhibins 4. Growth/Differentiation factors
29
Osteoclasts express ____ for removing _____
Proteases for removing ECM proteins
30
Osteoclasts express proteins that act as ____ to generate _____ (to reduce pH to dissolve mineral)
Proton pumps; H+ ions
31
Active osteoclasts have specialized _______ to increase the surface area in the resorption compartment
Ruffled border
32
Lifespan of osteoclasts:
Short (days)
33
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 ____
1. Normal bone growth and remodeling 2. Alveolar bone 3. Tooth roots; primary teeth 4. Alveolar bone; orthodontic tooth 5.Pathological conditions
34
Must occur to maintain bone shape
Modeling
35
Osteoclasts originally come from:
Hematopoietic Stem Cell (HSC)
36
During osteoclasts differentiation, the hematopoietic stem cell (HSC) will differentiate into:
CFU-M
37
During osteoclast differentiation: HSC —-> CFU-M—> _____
Monocyte
38
During osteoclast differentiation: HSC —-> CFU-M—> Monocyte —->
Mononucleated Osteoclasts (perfusion)
39
During osteoclast differentiation: HSC —-> CFU-M—> Monocyte —-> Mononucleated osteoclast (perfusion) —-> _____
Multinucleated osteoclast
40
During osteoclast differentiation: HSC —-> CFU-M—> Monocyte —-> Mononucleated osteoclast (perfusion) —-> Mutlinucleated osteoclasts ——> ____
Resorting osteoclast
41
What is the master transcription factor of osteoclast formation:
NFATc1
42
Osteoclast marker genes are associated with the function of the cell which include:
1. Fusion 2. Adherence to the bone surface 3. Acid production 4. Protease production
43
Which transcription factors are downstream of NFATc1?
C-fox & NFKB
44
There are two factors produced by osteoblasts/osteocytes that are essential for:
OCL differentiation
45
The two factors produced by osteoblasts/osteocytes that are essential for OCL differentiation include:
1. RANKL 2. M-CSF (aka CSF-1)
46
RANKL is a receptor activator of:
NFkB Ligand
47
M-CSF (aka CSF-a) is a ______ stimulating factor.
Macrophage colony
48
Promotes proliferation/survival of osteoclast precursors:
M-CSF
49
Member of the TNF superfamily that is required for osteoclast fusion and differentiation:
RANKL
50
Mater transcription factor that control osteoclasts differentiation:
NFATC1
51
Natural inhibitor of RANKL- a decoy receptor:
OPG (osteoprotogerin)
52
These osteoclast marker proteins fall under what category: 1. NFATc1 2. C-fos 3. NFkB
Transcription factors
53
These osteoclast marker proteins fall under what category: Tartrate resistant acid phosphatase (TRAP)
Enzyme
54
These osteoclast marker proteins fall under what category: 1. RANK 2. C-fms 3. Calcitonin 4. Integrin alpha-V-beta-3
Receptors
55
1.Receptor for RANKL 2.Receptor for M-CSF
RANK C-fms
56
These osteoclast marker proteins fall under what category: Carbonic a hydrate II & Vacuolar-type ATPase
Generates protons/proton pump
57
These osteoclast marker proteins fall under what category: Cathepsin K and MMP9, and MMP13
Proteases
58
Osteoclasts attach via ____ to form sealed zones
alpha-V-beta 3 integrins
59
In the mature resorbing osteoclasts, carbonic anhydrase II (CAII) functions to:
Generate protons
60
Vacuolated type H+ ATPase pumps protons into _____ which creates acid to ____.
Resorption lacuna; dissolve mineral
61
Exchangers on base lateral surface to remove excess bicarbonate
Cl- and HCO3-
62
In the mature resorbing osteoclast, _____ maintains the charge neutrality:
Chloride channel
63
______ is released into the resorption lacunae to digest matrix proteins:
Cathepsin
64
Impaired osteoclast function leads to:
Osteopetrosis
65
Osteopetrosis can be due to the failure in osteoclast ____ or osteoclasts form normally but have impaired ____
Formation; resorptive function
66
The two major clinical forms of Osteopetrosis:
1. Autosomal dominant 2. Autosomal recessive
67
Describe the autosomal dominant form of Osteopetrosis:
Adult benign type with relatively few symptoms
68
Describe the autosomal recessive form of Osteopetrosis:
Infantile malignant type, typically fatal if untreated in early childhood
69
In patients with Osteopetrosis, their bones are:
Abnormally dense; prone to fracture
70
Failed osteoclastic resorption affects: (3)
1. Bone growth 2. Remodeling 3. Tooth eruption
71
Osteopetrosis can be accompanied by: (8)
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
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
Alpha3; H+ ATPase
73
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:
Chloride channel
74
Pycnodysostosis is a specific form of Osteopetrosis caused by mutation in the:
Cathepsin K
75
What are the 3 genes that if mutated result in a form of osteopetrosis?
1. TGIRG1 2. CLCN7 3. Cathespin K
76
The TCIRG1 gene that gives rise to osteopetrosis (AR) is associated with: The CLCN7 gene that give rise to Osteopetrosis (AD) is associated with:
1. Vacuolar ATPase alpha3 subunit 2. Chloride channel
77
What factors can contribute to osteoporosis? (3)
Aging population, diet, and environmental factors
78
Osteoporosis is defined by a patient with a BMD ____ standard deviations below average for a healthy young person
2.5
79
Worldwide 1 in ____ women and 1 in ____ men over the age of 50 willl experience osteoporotic fractures
1 in 3 and 1 in 5
80
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 ____.
20-24% 5 years
81
Osteoporosis treatments can be directed at reducing ______, stimulating ______ or both.
Reducing bone resorption, stimulating bone formation, or both
82
Treatments for osteoporosis: Preferentially bind to hydroxyappetite. Inhibit osteoclast activity, by inhibiting the mevalonate pathway important for prenylation of GTPases
Amino bisphosphonates

Applied Biochem (18 decks)

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