2/27/17 Bone Formation - Regulation of Osteoblast / Differentiation and Bone Matrix Protein Formation Flashcards

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1
Q

Faster or slower remodeling in alveolar bone?

A

faster

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2
Q

Rapid remodelling of alveolar bone is assoc w:

A

tooth eruption and functional demands

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3
Q

alveolar bone vs. other bones in body:

A

comparable, basic cellular and matrix component consistent w other bones, cellular activities in formation + remodeling + regulating factor, too

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4
Q

Osteoclasts are found:

A

embedded in mineralized matrix

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5
Q

Harvesian systems are assoc with what bone type

A

clasts

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6
Q

This covers the outer layer of alveolar bone:

A

cortical plate

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7
Q

cortical plate extends from:

A

jaw

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8
Q

What forms the lingual and labial surfaces of the alveolar process?

A

cortical plate

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9
Q

What cover the inner spongy cancellous bone?

A

Cortical plate

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10
Q

These can be found in cancellous bone:

A

numerous marrow spaces w blood forming cells + osseous precursor cells

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11
Q

Higher remodelling rate, cortical plate or cancellous bone?

A

cancellous

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12
Q

Where do areas of remodeling occur throughout life?

A

discrete sites

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13
Q

These form a canopy over remodeling bone area:

A

osteomacs

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14
Q

Reversal cells are bw these 2 cell types

A

clasts –> mature blast and vice versa

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15
Q

Fxn of sclerostin:

A

cyte regulation

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16
Q

Phases of bone remodelling:

A

activation, resorption, reversal, formation, termination

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17
Q

Cells that can downregulate OPG:

A

bone lining cells

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18
Q

Cells that upregulate

A

B cells

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19
Q

Fxn of PTH

A

upregulate bone lining cells

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20
Q

Cells that upregulate MCP-1:

A

bone lining cells

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21
Q

Cell that upregulates csf-1:

A

bone lining cell2

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22
Q

2 sites where apoptotic cytes can be found:

A

activation, resorption

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23
Q

in which zones can cyte be found?

A

resorption, reversal, formation, termination

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24
Q

upregulates RANKL

A

bone lining cells

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25
Q

Cells that sclerostin is assoc w:

A

mature blasts, osteomacs, bone lining cells

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26
Q

From where do cells originate that lead to intramembranous bone formation?

A

cranial nerve crest, somites and lateral plate mesoderm

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27
Q

cranial nerve crest, somites and lateral plate mesoderm all undergo:

A

mesenchymal condensation

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28
Q

mesenchymal condensation of these cells leads to:

A

formation of cartilage anlage

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29
Q

What is endochondral ossification?

A

growth of caps around the cartilage anlagen (preexisting cartilage)

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30
Q

How are endochondarl bone then formed?

A

Hypertrophic cartilage w high-level VGF expression wrap around middle of cartilage to form bone collar

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31
Q

What types of bone are endochondral?

A

long bones

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32
Q

Cell type of cartilage:

A

chondrocyte

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33
Q

precursors for clasts:

A

monocyte/mac origin

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34
Q

TF? Blasts can become cytes or clasts.

A

T

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35
Q

Cells that synthesize matrix:

A

cytes

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36
Q

TF’s are aka:

A

nuclear proteins

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37
Q

TF? Each TF contain only one DNA binding site.

A

F. 1+

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38
Q

What are blasts and chondrocytes derived from?

A

mesenchymal precursor

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39
Q

These cells differentiate into chondrocytes:

A

mesenchymal cells

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40
Q

How does endochondral bone formation begin:

A

mesenchymal cells differentiate into chondrocytes

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41
Q

BPM sf:

A

bone morphogenic protein

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42
Q

Fxn of BMP:

A

act on mesenchymal stem cells to regulate differentiation

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43
Q

These all have important roles in commitment/ maintenance of chondrocyte phenotype:

A

Sox9, L-Sox-5 and Sox-6

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44
Q

These TFs are both require for blastic differentiation:

A

Run-2+ Osx-

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45
Q

Which expression starts first, Runx-2 or Osx?

A

Runx-2

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46
Q

These TFs downregulate Runx-2 activity

A

Twist famiiy

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47
Q

TFs that act on mesenchymal cell to differentiate to pre-chondrogenic cells:

A

BMPs and FGFs

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48
Q

TFs that act pre-chondrogenic cells to differentiate to early chondrocyte:

A

BMPs, FGFs, Wnts, Sox9, Sox5L, Sox6, B-catenin/TCF/LEF

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49
Q

TF’s that downregulate differentiation from columnar chondrocyte to hypertrophic chondrocyte:

A

BMPs, PTHrP

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50
Q

TF’s that upregulate differentiation from columnar chondrocyte to hypertrophic chondrocyte:

A

Runx2/3, Dlx5/6

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51
Q

Downregulates Runx2:

A

Twist 1,2

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52
Q

Upregulates differentiation from mesenchymal stem cell to pero-osteoblast:

A

Ihh, Runx 2

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53
Q

TFs that upregulate differentiation from pre-osteoblasts to osteoblast:

A

Osx, B-catenin, TCF, LEF

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54
Q

B-catenin, TCF, LEF upregulate these 2 differentiations:

A

pre-osteoblasts to osteoblast, pre-chondrogenic to early chondrocyte:

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55
Q

2 differentiations Runx2 upregulate:

A

columnar chondrocyte to hypertrophic chondrocyte, mesenchymal to pre-osteoblasts

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56
Q

TF regulating differentiation of mesenchymal stem cells to undergo mesenchymal condensation:

A

Sox9

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57
Q

These regulate transition from mesenchymal condensation chondrocytes:

A

Sox 5, 6, and 9

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58
Q

2 TFs that control blastic differentiation:

A

Runx2

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59
Q

What Positively controls maturation of chondrocytes to hypertrophy:

A

Runx2

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60
Q

What negatively controls maturation of chondrocytes to hypertrophy:

A

Sox 9

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61
Q

TF that has a role in both chondrocytic and osteoblastic differentiation:

A

Runx2

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62
Q

TF that provides specificity in osteoblastic differentiation:

A

Osterix

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63
Q

The only 2 TF leading from mesenchymal condensation in 2 steps to osteocytes:

A

Runx 2, Osterix

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64
Q

TF red for osteogenesis:

A

Runx2

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65
Q

Where is Runx 2 expressed?

A

mesoderm and osteoblast precursor cells

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66
Q

Mutation of Runx2 in animal models:

A

no binding to DNA: skeletal abnormalities (cleidocranial dysplasia)

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67
Q

TF needed or mesenchymal cells to diff to biopotential cells:

A

Ihh

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68
Q

TFs that upregulate dif of biopotential cells to preosteoblasts:

A

Wnt/B-catenin , Runx2

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69
Q

TFs that upregulate diff of preosteoblasts to osteoblasts:

A

Runx2

70
Q

Main TF in the regulation of osteoblast differentiation and proliferation during bone formation:

A

Osx and Wnt/B-catenin

71
Q

TF that initiates endochondral ossification:

A

Ihh

72
Q

Runx2 expressing biopotential progenitor cells an differentiate into:

A

either osteoblasts or chondrocytes

73
Q

TF that can inhibit the action of Wnt/B-catenin in the differentiation of osteoblast::

A

Osx

74
Q

What does the inhibition of Wnt/B-catenin lead to?

A

inhibition of osteoblast proliferation

75
Q

Col1a and ALP are markers of these cells:

A

biopotential cells, preosteoblasts and osteoblasts (low in bio, high in other 2)

76
Q

Identifying markers of osteoblasts:

A

Osx, Bsp, OC

77
Q

Bsp sf:

A

bone sialoprotein

78
Q

Where can Bsp be found?

A

ecm protein

79
Q

TF? 1 signaling pwy controls TF in osteoblast.

A

F. multiple

80
Q

Pwys that control TF’s in osteoblasts:

A

Ihh, glucocorticoids, Vit D, Wnt, Estrogens, PTH, TGFB, BPM2, FGF

81
Q

regulate proliferation and differentiation of ostebloasts (usually a reciprocal relationship between these 2)

A

Wnt/ B-catenin

82
Q

Cells slow/ speed in differentiation as they move toward differentiation:

A

slow

83
Q

These all act directly on Runx2 in osteoblast differentiation:

A

Ihh, glucocorticoids, B-Catenin, estrogen receptor, MAPK, Smads, FGF-R

84
Q

Fxn of BMP-R in osteoblast differentiation:

A

acts on both Smads and MAPK which both act directly on Runx2

85
Q

These act on TGFb-R, PTH-R, and ER respectively:

A

TGFB, PTH, Estrogens

86
Q

These all act directly on osteoblast gene differentiation:

A

B-catenin, Runx2, glucocorticoids, VDR

87
Q

What acts on VDR, leading to an influence on osteoblast gene differentiation directly thereafter?

A

Vit D

88
Q

Do blasts have PTH receptors?

A

yes

89
Q

Collagen levels increase/dec as cells differentiate:

A

osteoblasts

90
Q

Fxn of organic matrix of bone:

A

support and regulating the solid, inorganic C-P mineral phase of bone

91
Q

Predominant component of organic matrix of bone;

A

collagen, 95%, the rest are non-collagenous/ plasma proteins

92
Q

Cells that produce bone matrix:

A

osteoblasts

93
Q

Principle collagen type in mineralized bone:

A

1

94
Q

Collagen types that form heterotypic fiber bundles:

A

1 and 5

95
Q

What provides the basic structural integrity of CT in alveolar bone?

A

heterotypic fiber bundles made of Type 1 and 5 collagen

96
Q

Main producer of Type 3 collagen:

A

fibroblasts

97
Q

When is Type 3 collagen formed?

A

in formation of PDL

98
Q

Possible fxn of Type 12 collagen:

A

mechanical strength

99
Q

Collagen types in alveolar bone:

A

Type 1, 3, 12

100
Q

Common marker for alveolar bone:

A

Type 1 collagen

101
Q

Spaces where bone mineralization can occur

A

: in and between the collagen fibers

102
Q

What allows or unique deposition of mineral bw and within fibrils?

A

spatial distribution of collagen fibrils

103
Q

Shape of mature collagen:

A

triple helix

104
Q

Collagen triple helices form from:

A

nanoscale microfibrils which act as templates for the crystallization of HA nanocrystals

105
Q

The cells become bone-forming osteoblasts after signals from bone-specific proteins in the matrix:

A

undifferentiated bone-marrow stem cells that recognize collagen matrix

106
Q

What controls the chemotactic agent for sphingolin and allow migration of bone forming blasts to area

A

collagen fibrils

107
Q

Flow chart, progression from collagen triple helix to bone:

A

CTH, HA crystals + bone-marrow stem cells, bone forming osteoblast cells, bone

108
Q

Bone Resorption markers:

A

pyridinium cross-link collagen peptide fragments

109
Q

Bone formation markers:

A

Type-1 procollagen propeptides

110
Q

These are pyridinium cross-link collagen peptide fragments:

A

serum C-terminal telopeptide (ICTP), urine C-terminal telopeptide (Ctx), urine N-termianl telopeptide (NTx)

111
Q

These are Type-1 procollagen propeptides:

A

C-terminal propeptide fragments (P1CP), N-terminal propeptide fragments (PINP)

112
Q

These exposed when Type I collagen is broken down:

A

telopeptides

113
Q

serum ICTP is:

A

serum C-terminal telopeptide

114
Q

Elevated levels of these can be found in pts w osteoporosis, RA, paget’ disease and hyperparathyroidism:

A

serum ICTP and other pyridinoline X-links correlated w bone resorptive rate

115
Q

This can be used as a prognostic indicator in several metastatic bone tumors such as myeloma, prostate, lung and breast cancers:

A

Serum ICTP levels

116
Q

Dec in pyridinoline X-lins have been demonstrated in these pts:

A

postmenopausal osteoporotic subjects after bisphosphonate or estrogen therapy

117
Q

This may be a diagnostic marker of PDD:

A

GCF ICTP levels

118
Q

ICTP levels are strongly correlated w :

A

Cx parameters of perio tissue destruction

119
Q

Strong or weak connection bw elevated ICTP levels and implant failure?

A

strong

120
Q

osteocalcin is aka:

A

Bone GLA-protein

121
Q

osteocalcin:

A

bone binding protein, bone and dentin, maybe adipose tissue?, one of most abundant noncollagenous proteins in boone, Vit K dependent protein, made by blasts, complex functions

122
Q

TF? Vit K dependent protein is a clotting protein.

A

F

123
Q

TF? Osteocalcin is directly related to initiation of mineralization.

A

F

124
Q

Fxns of osteocalcin:

A

regulation of mineralization or bone turnover, chemoattractant, recruiting clasts to resorptive sites, marker to asses remodelling/bone formation in systemic bones

125
Q

Fxn of osteocalcin in dentistry:

A

Level in GCF to monitor tooth movement in ortho, bone-specific marker of bone turnover but not as predictive indicator of PDD

126
Q

This triggers the production o insulin by B cells:

A

osteocalcin

127
Q

Why might osteocalcin be a tx or Type II diabetes?

A

signals fat cells to release adiponectin which inc insulin sensitivity, possible bone, fat cell communication

128
Q

Insulin signaling in bone favors whole body glucose homeostasis by:

A

activating osteocalcin

129
Q

Insulin signalling pwy to bone:

A

signals blasts, which communicate w clasts to resorb old bone, low pH results in area of new resorption, activating osteocalcin in bone matrix, which is released from bone and travels to pancreas to stimulate release of more insulin

130
Q

Bone has properties of an endo/exo crine organ:

A

endocrine, suggests osteocalcin could be a hormone

131
Q

Accounts for 15% of noncollagenous ECM proteins:

A

Osteonectin

132
Q

Is osteonectin present in CT?

A

yes, but 104X higher in bone

133
Q

Fxn of osteonectin:

A

unknown

134
Q

osteonectin has high affinities for:

A

collagen, HA

135
Q

When do animal studies suggest osteonectin is formed:

A

once woven bone matures

136
Q

This may serve as a potentiatior for and marker o flate bone formation/ maturity:

A

osteonectin

137
Q

What has osteonectin be localized to on mRNA during fracture healing?

A

osteoblasts and hypertrophic chondrocytes

138
Q

Role of GF’s during bone repair:

A

Regulation of cell proliferation, chemotaxis, differentiation, matrix synthesis

139
Q

Bone GF’s are conc here:

A

in matrix

140
Q

When are bone GF”s released?

A

during resorption

141
Q

29 bone GF’s:

A

TGFB, VEGF, BMPs 1-15, FGF 1-9, PDGF A, B, AB

142
Q

GF that may have a role in modulated guided tissue regenerative therapy:

A

PDGF, can migrate to defect and fix

143
Q

PDGF has a potent chemotactic and mitogenic effect on:

A

PDL fibroblasts

144
Q

Scaffold to keep PDGF in place at site of bone repair:

A

Tricalcium phosphate carrier

145
Q

PDGF can stimulate the growth of both:

A

bone and PDL

146
Q

GF enhanced matrix is used to repair these perio defects:

A

inrabony/ furcation defect, gingival recession assoc w perio defects

147
Q

What is the matrix component of GEM?

A

Beta-TCP

148
Q

MOA is osseous wound:

A

brings precursor cells to defect area

149
Q

mitogenesis is aka:

A

proliferation

150
Q

GEF is made of:

A

bioactive protein rhPDGF, highly purified recombinant human PDGF and osteoconductive matrix B-TCP

151
Q

GEF stimulates this cell of the periodontium the most:

A

fibroblast, then perivasicular cells

152
Q

Cells stimulated by PDGF in the periodontium:

A

Fibroblasts, perivasicular cells, endothelial cells, osteoblasts, cementoblasts

153
Q

Steps to using GEM:

A

soak B-TCP scaffold in fhPDGF-BB for 10m, debride defect, fill w GEM to alveolar crest

154
Q

How long doe it take for release of rhPDGF-BB after placement of GEM:

A

minutes

155
Q

GEM tx with B-TCP scaffold in fhPDGF-BB leads to replacement of these structures:

A

new alveolar bone, PDL, cementum

156
Q

Will B-TCP alone lead to bone regeneration?

A

yes, not much less than w PDGF

157
Q

Which provides more bone fill, B-TCP alone or that with PDGF?

A

w PDGF

158
Q

FGF-2 stimulates:

A

perio tissue regeneration & clinical attachment level, bone regeneration

159
Q

What is rhBMP-2 used for?

A

bone grafting

160
Q

MOA of rhBMP-2:

A

implantation, chemotaxis, proliferation, differentiation, bone formation and Angiogenesis, Remodeling, normal trabecular bone

161
Q

Cells that come to implantation site after rhBMP-2 placement:

A

mesenchymal stem cell, other bone forming cells

162
Q

When do the cells multiply after rhBMP-2 placement?

A

before differentiation

163
Q

This can enhance surgical soft and hard tissue wound healing:

A

platelet-rich plasm

164
Q

Source of PRP:

A

autologous source of PDGF

165
Q

GF”s are produced by:

A

blasts and platelets

166
Q

Major growth factors present in PRP:

A

PDGF (AA, BB, AB), TGF-B, EGF, IGF-1

167
Q

What’s needed for the therapeutic effect of PRP?

A

concentration of platelets, 40-500%inc, 1million/ microliter in 5ml

168
Q

Volume of blood typically needed from a pt for an oral bony defect:

A

20-60mL

169
Q

Disadv of PRP use:

A

need to activate platelets, usually w thrombin or CaCl2, variability in platelet conc, disagreement as to usefulness of PRP

170
Q

Cx proc in which PRP has been successful:

A

infrabony defects, inflammatory lesion, mucogingival proc, 3rd molar extraction healing, osseointegration in implant placement