Oral Tissues, Osteoblasts, Osteocytes and Osteoclasts Flashcards

1
Q

Which growth factor in osteoclast differentiation acts between CFU-M and the formation of the monocyte?

A

M-CSF

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2
Q

Which cells assist in:

  • bone resorption during bony remodeling
  • removal of alveolar bone during tooth eruption
  • resorption of primary tooth roots
  • orthodontic tooth movement
  • bone loss in pathological conditions?
A

osteoclasts

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3
Q

What does OPG do?

A

inhibits the process of osteoclast differentiation

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4
Q

Are osteoclasts derived from the same origin as osteocytes and osteoblasts?

A

NO

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5
Q

What is a natural inhibitor of mineralization in the body?

A

PPi

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6
Q

What cells control the responses of bone cells in regards to their mechanical load?

A

osteocytes

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7
Q

What cells make up over 90% of all bone cells?

A

osteocytes

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8
Q

What are the growth factors regulating osteoblast differentiation?

A
BMPs**
TGF-beta
WNT/B-catenin**
Hedgehog
IGF-1
PTH and PTHrP
FGFs
Notch pathway
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9
Q

What anabolic agent used in the treatment of osteoporosis stimulates bone formation, partly through the inhibition of sclerostin?

A

PTH 1-84

Teriparitide

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10
Q

Which growth factor in osteoclast differentiation acts between the monocyte and the mononucleated/prefusion osteoclast?

A

M-CSF

RANKL

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11
Q

What do mesenchymal progenitors give rise to?

A

myocytes
adipocytes
hypertrophic chondrocytes
osteoblasts

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12
Q

Which cells are embedded within the mineralized bone matrix?

A

osteocytes

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13
Q

Normally, estrogen is inhibiting ____ bone resorption.

A

osteoclast

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14
Q

____ are associated with mortality rates of up to 20-24% in the first year.

A

Hip fractures

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15
Q

___ consists of all the matrix proteins that these cells produce, particularly Type I collagen.

A

osteoid

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16
Q

Mechanosensory capabilities, control of bone resorption and formation, regulation of mineralization, and regulation of mineral homeostasis (Ca, Ph) are all functions of?

A

osteocytes

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17
Q

Why is the osteocyte a key target cell for the development of new treatments for diseases of bone loss and bone growth?

A

because of its very specific use and inclusion of sclerostin in their pathways

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18
Q

What are the osteoclast marker protein pumps?

A

carbonic anhydrase

vacuolar-type ATPase

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19
Q

What does cathepsin K do?

A

digests matrix proteins

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20
Q

What channel in a mature resorbing osteoclast maintains the charge neutrality?

A

Cl (chloride) channel

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21
Q

In _____, bone formation can’t keep up with bone destruction.

A

osteoporosis

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22
Q

What are the 3 major mutations associated with osteopetrosis?

A
  • mutations in a3 subunit of vacuolar H+ ATPase
  • mutations in Cl channel in osteoclast
  • cathepsin K mutations
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23
Q

What marker would you find in a matured, late osteocyte?

A

SOST

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24
Q

What enzyme is indicative of an osteoblast?

A

alkaline phosphatase

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25
Q

What pathway is important in determining bone mass?

A

Wnt/B-catenin

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26
Q

Osteoclasts are derived from the same precursors as ___, which is the ___ lineage.

A

macrophages; hematopoietic

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27
Q

Which transcriptional regulator drives the terminal differentiation of osteoblasts into osteocytes, lining cells, and apoptotic cells?

A

B-catenin

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28
Q

Which two transcription factors are imperative for osteoblast formation and differentiation?

A

Runx2

Osterix

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29
Q

What enzyme that is active in a mature, resorbing osteoclast generates the protons needed to create an acidic pH?

A

carbonic anhydrase II (CAII)

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30
Q

At what stage of osteoclast differentiation are NFATc1, C-fos, and NFKB acting at?

A

the mononucleated (pre-fusion) osteoclast stage

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31
Q

Activating and inactivating mutations of Lrp5 lead to ___ and ___ bone mass, respectively.

A

high; low

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32
Q

In mutations where sclerostin is ___, a high bone mass phenotype is expressed; when sclerostin is ___, a low bone mass phenotype is expressed.

A

absent/null; overexpressed/gain-of-function

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33
Q

What is the process called that dissolves and repairs bone through osteoclasts and osteoblasts in equlibrium?

A

bone remodeling process

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34
Q

Which growth factor allows the progression of the macrophage precursors into monocytes?

A

M-CSF

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35
Q

What does the mutation that causes Stone Man syndrome, BMP type 1, cause in regards to ligands?

A

it causes mild constitutive action of the ligand, allowing receptor activation without the ligand actually being present

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36
Q

What would OPG prevent the progression of?

A

maturation of a fused and differentiated osteoclast by preventing the formation of its precursors

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37
Q

Why has hormone replacement therapy been replaced by SERMs?

A

because SERMs do not have harmful side effects on the uterus and breasts

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38
Q

What are some early osteocyte markers?

A

E11/gp/podoplanin
DMP1
MEPE
PHEX

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39
Q

____ is an antibody against RANKL and inhibits osteoclast formation.

A

Denosumab

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40
Q

If you increase your Wnt/B-catenin activation, then ___ bone mass results.

A

high

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41
Q

What ligand promotes the fusion of the osteoclast in the osteoclast differentiation pathway?

A

RANKL

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42
Q

The reduced activities of what can lead to hypophosphatasia?

A

alkaline phosphatase

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43
Q

Which transcriptional regulators drive the differentiation of immature osteoblasts into mature osteoblasts?

A

Osterix

B-catenin

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44
Q

What classification of osteoporosis treatment are PTH 1-84, Teriparitide, and anti-sclerostin antibodies?

A

anabolic agents

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45
Q

What are the 3 transcription factors that regulate the prefusion osteoclasts during their differentiation?

A

NFATc1
C-fos
NFKB

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46
Q

What marker is highly expressed in mature osteocytes, cementocytes, and odontoblasts?

A

sclerostin (SOST)

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47
Q

___ is required for osteoclast fusion and differentiation.

A

RANKL

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48
Q

In ___, bones are abnormally dense, yet prone to fracture and often result in scoliosis, nerve compression, tooth eruption issues, and impaired marrow function among other symptoms.

A

osteopetrosis

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49
Q

What is a late osteocyte marker?

A

Sclerostin (SOST)

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50
Q

_____ plays an important role in mineralization of bone.

A

Alkaline phosphatase

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51
Q

What is the master transcription factor of osteoclast formation?

A

NFATc1

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52
Q

Rank osteoblasts, osteoclasts, and osteocytes from shortest lifespan to longest lifespan.

A

osteoclasts&raquo_space; osteoblasts&raquo_space; osteocytes

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53
Q

Which transcriptional regulators drive the differentiation of osteochondrogenic precursors into immature osteoblasts?

A

Runx2

B-catenin

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54
Q

____ express proteins that act as proton pumps to generate H+ ions to reduce pH and dissolve mineral.

A

Osteoclasts

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55
Q

In mutations where sclerostin is ___, a high bone mass phenotype is expressed; when sclerostin is ___, a low bone mass phenotype is expressed.

A

absent/null; overexpressed/gain-of-function

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56
Q

Which cells are responsible for bone formation and are located on the surface of the bone?

A

osteoblasts

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57
Q

What are RANKL and M-CSF produced by?

A

osteoblasts and osteocytes

58
Q

What is the role of the Cl and HCO3 exchanger?

A

it removes excess bicarbonate

59
Q

What is fibrodysplasia ossificans progressiva, or “Stone Man syndrome,” characterized by?

A

heterotopic bone formation that fuses joints, ribs and other parts of the body with new bone

60
Q

____ is the loss of bone mass, often associated with menopause or aging.

A

Osteoporosis

61
Q

Osteoblasts, chondrocytes, myoblasts, and adipocytes were all differentiated from a common _____.

A

mesenchymal precursor

62
Q

What proteins promote the differentiation from early progenitor cells in osteoblast differentiation?

A

BMPs

63
Q

At what stage of osteoclast differentiation is RANKL working at?

A

pre- and post-formation of the multinucleated osteoclast

64
Q

What anti-resorptive binds to hydroxyapatite and inhibits the activity of osteoclasts by inhibiting the melavonate pathway?

A

bisphosphonates

65
Q

What happens to GSK-3B when Wnt is NOT bound to the receptor?

A

it tags B-catenin to be degraded so it cannot act as a transcription factor

66
Q

What happens if the transcriptional regulator Runx2 stays on too long in osteoblast differentiation?

A

it can inhibit maturation and terminal differentiation

67
Q

Bisphosphonates have a high affinity for ____.

A

hydroxyapatite

68
Q

Which enzyme is an osteoclast marker protein?

A

TRAP (tartrate resistant acid phosphatase)

69
Q

Can osteoclasts remove ECM proteins, too?

A

YES - express proteases for removing ECM proteins like collagen

70
Q

What measure constitutes osteoporosis?

A

a patient having a bone mass density >2.5 standard deviations below the average

71
Q

Sclerostin inhibits ___ to shut down the activating mutation that leads to high bone mass.

A

Wnt binding to its receptor

72
Q

What are the two major clinical forms of osteopetrosis?

A

= autosomal dominant - adult type - few symptoms

= autosomal recessive - infantile type - typically fatal

73
Q

The severity of hypophosphatasia varies due to the relative loss of ___.

A

alkaline phosphatase

74
Q

___ cells are quiescent cells that lie on top of the new bone built up by the osteoblasts.

A

Lining

75
Q

Human mutations in SP7 (Osterix) is associated with what disease?

A

osteogenesis imperfecta XII

76
Q

Which disease is characterized by hypoplastic or aplastic bony areas, delayed ossification of midline structures, supernumerary teeth, missing clavicles, and prognathic mandible due to a hypoplastic maxilla?

A

Cleidocranial dysplasia

77
Q

___ is a master transcription factor for bone.

A

Runx2

78
Q

What is the cause of osteopetrosis?

A

impaired osteoclast function (either from failed formation OR impaired function)

79
Q

Why would antibodies to sclerostin be a potentially beneficial treatment for patients with osteoporosis?

A

because inhibiting sclerostin would remove the “brake” of the Wnt/B-catenin pathway and allow for more bone to be made

80
Q

What happens when Wnt IS bound to the receptor?

A

GSK-3B is phosphorylated, which releases B-catenin and allows it to travel to the nucleus and activate gene transcription

81
Q

How long do osteocytes live?

A

decades

82
Q

Which key signaling pathway is present between the mesenchymal stem cell and osteochondrogenic precursors in the proliferation phase?

A

BMPs (2, 7)

83
Q

What does an osteoclast need to do?

A
  • differentiate and fuse
  • adhere to bone surface
  • produce acid for bone
  • produce proteases for ECM
  • respond to factors to allow it to survive/act
84
Q

What is it called when bones forms inappropriately in soft tissues?

A

heterotopic bone formation

85
Q

Which type of cell in the bone is multinucleated and is responsible for removing bone?

A

osteoclasts

86
Q

In bony remodeling, as osteclasts resorb bone, they release ____ that attract osteoblasts.

A

chemotactic factors

87
Q

What ECM proteins are indicative of an osteoblast?

A

Type I collagen
osteopontin
osteocalcin
bone sialoprotein (BSP)

88
Q

When Osterix is knocked out, does bone eventually form?

A

NO - the cartilage is mineralized but does not progress to bone

89
Q

What classification of osteoporosis treatment are bisphosphonates, hormone replacement therapy, selective estrogen receptor modulators, denosumab, and cathepsin K inhibitors?

A

anti-resorptives

90
Q

What is the natural inhibitor of RANKL?

A

OPG

91
Q

Which osteoblast genes does Osterix control the expression of?

A

Type I collagen
Osteocalcin
Osteopontin

92
Q

Which growth factor in osteoclast differentiation acts before and after the formation of the multinucleated osteoclast to promote the macrophage precursor into the
osteoclast lineage?

A

RANKL

93
Q

Can the WNT/B-catenin pathway inhibit osteoblast differentiation?

A

YES - if the signals are turned on too early

94
Q

Are osteocytes terminally differentiated osteoblasts?

A

YES

95
Q

Do osteocytes play a role in homeostasis?

A

YES - they play a role in the endocrine regulation of phosphate homeostasis

96
Q

Which enzyme pumps the protons into the resorption lacuna to allow the osteoclast to dissolve the mineral?

A

vacuolar-type H+ ATPase pumps

97
Q

What transcription factors are indicative of an osteoblast?

A

Runx2

Osterix

98
Q

What is BONJ attributed to?

A

the suppression of bone turnover occurred through the inhibition of osteoclast activity

99
Q

What does the deletion of the SOST gene result in?

A

sclerostosis or Van Buchem’s disease

100
Q

Which key signaling pathway is present between the mature osteoblast and terminally differentiated cells?

A

WNT/B-catenin

101
Q

What happens if the Runx2 gene is lacking?

A

cartilage fails to mineralize or bones may not form

102
Q

___ mutations generally lead to reduced levels of a protein, generally.

A

Missense

103
Q

Mutations in what protein causes Stone Man syndrome?

A

BMP type I receptor

104
Q

Would bisphosphonates have an effect on orthodontic tooth movement?

A

YES

105
Q

Worldwide, how many women and men will experience osteoporotic fractures?

A

1 in 3 women

1 in 5 men

106
Q

Which key signaling pathway is present between the immature osteoblast and mature osteoblast in the maturation phase?

A

WNT/B-catenin

107
Q

What is the primary transcription factor in osteocytes?

A

Mef2c

108
Q

How do osteoclasts attach to the bone surface?

A

through aB3 integrins

109
Q

Which transcriptional regulator is important in the proliferation, maturation, AND terminal differentiation of osteoblasts?

A

B-catenin

110
Q

Osteoblasts originate from ____ cells.

A

mesenchymal stem

111
Q

What bone cells produce large amounts of ECM proteins, such as type I collagen, that eventually mineralizes?

A

osteoblasts

112
Q

What does the knockout of specific BMPs lead to?

A

skeletal defects

113
Q

Do we see osteoclast activity in normal bone growth?

A

YES

114
Q

What are some osteoclast marker protein receptors?

A

RANK (for RANKL)
C-fms (for M-CSF)
calcitonin receptor
integrin avB3

115
Q

____ hydrolyzes pyrophosphate (PPi), a natural inhibitor of mineralization, which increases local phosphate concentration and promotes mineralization.

A

Alkaline phosphatase

116
Q

Alkaline phosphatase promotes ____.

A

mineralization

117
Q

What are two osteoclast marker protein proteases?

A

cathepsin K

MMP9, MMP13

118
Q

What happens if the transcriptional regulator B-catenin appears too early in osteoblast differentiation?

A

it can actually inhibit the processes of proliferation

119
Q

FGF23, DMP1, and PHEX are all genes important in ____.

A

phosphate homeostasis

120
Q

____ prevent patients from losing further bone but do not build back the bone lost.

A

Anti-resorptives

121
Q

What does M-CSF promote the proliferation and survival of?

A

osteoclast precursors

122
Q

What drives osteoblast differentiation?

A

key transcriptional regulators that signal progression into next phase

123
Q

Alkaline phosphatase is an enzyme highly expressed in ___ and ___.

A

osteoblasts; odontoblasts

124
Q

Which primary transcription factor regulates the mononucleated (prefusion) osteoclast in osteoclast differentiation?

A

NFATc1

125
Q

What would a histological section of osteonecrosis look like? What wouldn’t be present?

A

necrotic bone with empty osteocyte lacunae; osteocytes

126
Q

What pH is needed to dissolve bone mineral in the osteoclast’s resorption bays?

A

4.5

127
Q

_____ proteins promote differentiation from early osteoprogenitor cells in osteoblast differentiation.

A

Bone morphogenic proteins (BMPs)

128
Q

The loss of ____ leads to increased bone resorption.

A

estrogen

129
Q

In humans, mutations in the ____ gene is associated with hypophosphatasia.

A

alkaline phosphatase

130
Q

Osteoblasts and osteocytes produce RANKL receptors on their cell surfaces and secrete M-CSF. How do these two factors promote proliferation of osteoclast precursors?

A

M-CSK binds to receptors on the osteoclast precursor cell, which then allows RANK on the osteoclast precursor to bind to the RANKL receptor on the osteblast/osteocyte; these two actions together allow the maturation of a differentiated osteoclast

131
Q

___ is a negative regulator of bone formation, in that it acts as a “brake” to limit the formation of bone.

A

Sclerostin (SOST)

132
Q

In osteopetrosis, why must hematopoiesis often migrate to other locations to maintain function?

A

the marrow cavities shrink and become very narrow

133
Q

What are BMPs required for?

A

skeletal development and maintenance of adult bone homeostasis

134
Q

___ are the main producer of Type I collagen in bone.

A

Osteoblasts

135
Q

___ is a rare, heritable rickets or osteomalacia due to reduced activity of alkaline phosphatase.

A

Hypophosphatasia

136
Q

___ flatten to become a lining cell.

A

Osteoblasts

137
Q

____ have proven to be useful in treating patients with cancer who have high serum calcium levels.

A

Bisphosphonates

138
Q

What does sclerostin (SOST) do to the Wnt/B-catenin pathway?

A

it shuts it down as to limit the excess formation of bone

139
Q

What structure allows for the dissolution of bone?

A

the ruffled border of the osteoclast

140
Q

Which key signaling pathway is present between the osteochondrogenic precursors and immature osteoblasts, entering the maturation phase?

A

WNT/B-catenin

141
Q

Runx2 induces another transcription factor called ____, which is also critical for osteoblast differentiation.

A

Osterix