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Applied Biochem > Biochemistry Of Bone Formation- Exam V > Flashcards

Biochemistry Of Bone Formation- Exam V Flashcards

1
Q

What are the 4 phases of skeletal development?

A
  1. Migration of preskeletal cells to sites of future skeletogenesis
  2. Interaction of these cells with epithelial cells
  3. Mesenchymal condensation
  4. Cell differentiation
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2
Q

During the migration phase of preskeletal cells during skeletal development , where do they migrate to?

A

The future sites of skeletogenesis

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3
Q

During skeletal development, the interaction of what types of cells leads to mesenchymal condensation?

A

Epithelial-mesenchymal interaction

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4
Q

Following the condensation phase of skeletal development, what can the cells differentiate into?

A

Chondroblasts or osteoblasts

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5
Q

What is the indirect method of bone formation?

A

Endochondral

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6
Q

In endochondral bone formation, what does the mesenchyme first form?

A

Cartilage template

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7
Q

In endochondral bone formation, the cartilage template forms in what shape?

A

Shape of future bone

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8
Q

In endochondral bone formation, the cartilage template will later be replaced by:

A

Mineralized bone tissue

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9
Q

What type of bone formation occurs in most bones in the skeleton, especially bones that bear weight and have joints?

A

Endochondral bone formation

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10
Q

What process of bone formation involves direct bone formation?

A

Intramembranous

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11
Q

In Intramembranous bone formation, describe the transformation of cells

A

Direct transformation of mesenchymal cells to osteoblasts (no cartilage intermediate)

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12
Q

What type of bone formation is restricted to the cranial vault, some facial bones, and parts of the mandible and clavicle

A

intramembranous bone formation

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13
Q

What type of bone formation contributes or occurs during fracture repair?

A

both Endochondral and intramembranous

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14
Q

In step 1 of Endochondral bone formation- the mesenchymal cells will initially condense to form _____, that will show the future shape of the bone

A

cartilage model

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15
Q

In step 2 of endochrondral bone formation- after the cartilage model is formed, differnetaon and formation of ____ occur.

A

a mineralized collar (sleeve of bone)

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16
Q

In step 3 of endochrondral bone formation- the collar mineralization causes the chondrocytes in the center to undergo:

A

hypertrophy

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17
Q

When chondrocytes swell up, change their gene expression patterns and start to calcify. They also secrete a growth factor

A

hypertrophy

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18
Q

When the chondrocytes undergo hypertrophy, what growth factor do they secrete?

A

VEG F (vascular endothelial growth factor)

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19
Q

In step 4 of endochrondral bone formation - What does the VEG F secreted by the chondrocytes during hypertrophy do?

A

attracts blood vessels to invade

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20
Q

The primary ossification center in Endochondral bone formation is in:

A

medullary cavity

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21
Q

In Endochondral bone formation when the blood vessels invade the cartilage template, what do they bring in with them?

A

osteogenic precursor cells & osteoclasts

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22
Q

In endochrondral bone formation, osteoclasts will resorb the :

A

mineralized cartilage matrix

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23
Q

In endochondral bone formation, what process occurs by the osteogenic precursor cells?

A

osteogenesis

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24
Q

In endochondral bone formation, the osteogenesis from the osteogenic precursor cells brought in by the blood vessels causes the formation of: (2)

A

the marrow cavity and trabecular bone

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25
Q

In endochondral bone formation of a long bone, what occurs ~age 14-20?

A

growth plate fusion

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26
Q

Key transcriptional regulators of osteoblast differentiation: Key transcriptional regulators of osteoblast differentiation: It is imperative that the Runx2, Osterix, and B-catenin act:

A

Appropriate amount of time

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27
Q

Key transcriptional regulators of osteoblast differentiation: What transcriptional regulator functions to push the osteogenic precursor to the immature osteoblast?

A

Runx2 & Beta-catenine

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28
Q

Key transcriptional regulators of osteoblast differentiation: If beta-catenin acts on the mesenchymal cells too early in proliferation, what will result?

A

It will inhibit the transition from mesenchymal stem cells to osteochondrogenic precursers

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29
Q

Key transcriptional regulators of osteoblast differentiation: What trascriptional regulators function to push the immature osteoblast to the mature osteoblast in the maturation phase:

A

Osterix & B-catenin

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30
Q

If Runx 2 acts on the immature osteoblast for too long during the maturation phase, what is the result?

A

It will prevent further differentiation

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31
Q

What transcriptional factor is responsible for the transition of mature (matrix producing) osteoblasts to the terminally differentiated states?

A

B-catenin

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32
Q

What are the terminally differentiated states of the osteoblast?

A

osteocyte, lining cells, apoptosis

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33
Q

Label the green boxes for the appropriate transcriptional factors acting: (OSTEOBLAST DIFFERENTIATION)

A

left to right:

Runx2 & B-Catenin

Osterix & B-Catenin

B-Catenin

34
Q

B-Catenin is involved in:

A

WNT signaling pathway

35
Q

____ comes on at an early stage pushing the precursors from the chonrogenic to the osteoblastic phenotype

A

Runx2

36
Q

_____ comes on in a later phase pushing the immature osteoblast to a mature osteoblast:

A

Osterix

37
Q

If you take a mouse and KO the Runx2 gene, you end up with a mouse with:

A

only a cartlaginous skeleton, doesn’t ever mineralize to bone

38
Q

In humans with a complete knockout of Runx2, this will result in a:

A

non-viable fetus

39
Q

A heterozygous mutation of Runx2 in humans causes:

A

cleidocranial dysplacia (CCD)

40
Q

Runx2 is a master transcription factor essential for:

A

bone and tooth development

41
Q

Cleidocranial dysplasia is caused by what type of mutation?

A

Autosomal dominant

42
Q

CCD result from ____ in Runx2

A

happloinsufficiency

43
Q

Inactivating mutation/deletion in one allele:

A

Haploinsufficiency

44
Q

Disease characterized by delayed ossification of midline structures of the body (especially membraneous bone)

A

Cleidocranial dysplasia

45
Q

In CCD:

  1. _____ are partly or completely missing
  2. Late closing of ______
  3. Describe teeth
  4. ____ mandible due to _____ of maxilla
A
  1. Clavicles
  2. Fontanelle
  3. Supernumerary teeth
  4. Prognathic mandibule (protruding) due to hypoplasia of maxilla
46
Q

What transcription factor is downstream of Runx2

A

Osterix

47
Q

What transcription factor does Runx2 induce?

A

Osterix

48
Q

Mice lacking osterix have:

A

impaired osteoblast fomration

49
Q

Gene name for Ostrix:

A

SP7

50
Q

Osterix contorls expression of what osteoblast genes?

A

Type 1 collagen, osteocalcin, and osteopontin

51
Q

Human mutations in SP7 (osterix) are associated with:

A

osteogenesis imperfecta type 7

52
Q

What are two important key signaling pathways that regulate osteoblasts differentiation:

A

BMPS & WNT/B-catenin signaling pathway

53
Q

What important key signaling pathways comes first when regulating osteoblast differentiation?

A

BMP2,7

54
Q

If signaling of the WNT/B-catenin pathway occurs too early, what will occur?

A

Inhibit the mesenchymal cells from differentiation into osteogenic precursers

55
Q

Originally purified from bone extracts that induce toe formation when implanted in muscle (ectopic bone assay)

A

BMPS

56
Q

BMPs are required for ______ of adult bone homeostasis

A

skeletal development/ maintenance

57
Q

BMPs promite differentiation from:

A

early osteoprogenitor cells

58
Q

BMPs are importation in:

A

fracture healing

59
Q

Knockout of specific BMPs leads to:

A

skeletal defects:

60
Q

Naturally occurring mutations in BMPs where their receptors result in:

A

inherited skeletal disorders in humans

61
Q

A disease characterized by heterotopic bone formation:

A

Fibrodysplasia ossificans progressa

62
Q

Stone man syndrome:

A

Fibrodysplasia ossifications progressa

63
Q

Where does the bone form in fibrodysplasia ossificans progressa?

A

soft tissue

64
Q

In FOP cases, surgical treatment is not an option because:

A

bone forms in response to tissue trauma

65
Q

What is the mutation and what gene causes fibrodysplasia ossificans progressiva

A

mutation in: BMP type 1 receptor- gene is ACVR1 (single AA substitution)

66
Q

The mutation involved in FOP causes mild _____ and ____ with BMP ligand binding.

A

constitutive activation and over activation with BMP ligand binding

67
Q

In addition to the constitutive activation and over activation with BMP ligand binding, in FOP, there is also aquired responsiveness to:

A

Activin A

68
Q

What treatments have been looked into regarding FOP?

A

Antibodies against active A and kinase inhibitors elective for mutant receptor

69
Q

WNT/B-catenin signaling:

Under normal circumstances where there is no WNT to simulate its receptor, the B-catenin will be:

A

phosphorylated by GSK-3beta

70
Q

WNT/B-catenin signaling:
When B-catenin is phosphorylated by GSK-3Beta,

A

B-catenin will go be degraded in the cell

71
Q

WNT/B-catenin signaling:
Describe the receptor for the WNT ligand

A

LRP5+LRP+Frizzled

72
Q

WNT/B-catenin signaling:
When WNT binds its receptor complex, that will then come in and phosphorylate the GSK-3B which will now:

A

release B-catenine

73
Q

When the GSK-3B releases the B-cat, this allows for the B-Cat to go to the _____ and interact with a protein called ____ and then initiate ____.

A

nucleus; TCF; initiate gene transcription

74
Q

WNT/B-catenin signaling:

When the b-catenin is able to get inside the nucleus, interact with TCF and initiate gene transcription, this will ultimately lead to:

A

Osteogenesis (bone formation)

75
Q

signaling pathway important in determining bone mass:

A

WNT-B-catenin pathway

76
Q

Activating mutation in LRP5 lead to:

A

high bone mass in humans

77
Q

Inactivating mutations of LRP5 lead to:

A

low bone mass

78
Q

Mechanism of bone mineralization- The first phase of mineralization initiated by:

A

matrix vesicle mediated mechanism

79
Q

Mechanism of bone mineralization: The second phase of mineralization involves:

A

Propagation of mineralization on collagen fibers

80
Q

Extracellular membrane bound vesicles produced by osteoclasts:

A

matrix vesicles

Applied Biochem (18 decks)

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