2/27/17 Bone Formation - Regulation of Osteoblast / Differentiation and Bone Matrix Protein Formation Flashcards
1
Q
Faster or slower remodeling in alveolar bone?
A
faster
2
Q
Rapid remodelling of alveolar bone is assoc w:
A
tooth eruption and functional demands
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
4
Q
Osteoclasts are found:
A
embedded in mineralized matrix
5
Q
Harvesian systems are assoc with what bone type
A
clasts
6
Q
This covers the outer layer of alveolar bone:
A
cortical plate
7
Q
cortical plate extends from:
A
jaw
8
Q
What forms the lingual and labial surfaces of the alveolar process?
A
cortical plate
9
Q
What cover the inner spongy cancellous bone?
A
Cortical plate
10
Q
These can be found in cancellous bone:
A
numerous marrow spaces w blood forming cells + osseous precursor cells
11
Q
Higher remodelling rate, cortical plate or cancellous bone?
A
cancellous
12
Q
Where do areas of remodeling occur throughout life?
A
discrete sites
13
Q
These form a canopy over remodeling bone area:
A
osteomacs
14
Q
Reversal cells are bw these 2 cell types
A
clasts –> mature blast and vice versa
15
Q
Fxn of sclerostin:
A
cyte regulation
16
Q
Phases of bone remodelling:
A
activation, resorption, reversal, formation, termination
17
Q
Cells that can downregulate OPG:
A
bone lining cells
18
Q
Cells that upregulate
A
B cells
19
Q
Fxn of PTH
A
upregulate bone lining cells
20
Q
Cells that upregulate MCP-1:
A
bone lining cells
21
Q
Cell that upregulates csf-1:
A
bone lining cell2
22
Q
2 sites where apoptotic cytes can be found:
A
activation, resorption
23
Q
in which zones can cyte be found?
A
resorption, reversal, formation, termination
24
Q
upregulates RANKL
A
bone lining cells
25
Cells that sclerostin is assoc w:
mature blasts, osteomacs, bone lining cells
26
From where do cells originate that lead to intramembranous bone formation?
cranial nerve crest, somites and lateral plate mesoderm
27
cranial nerve crest, somites and lateral plate mesoderm all undergo:
mesenchymal condensation
28
mesenchymal condensation of these cells leads to:
formation of cartilage anlage
29
What is endochondral ossification?
growth of caps around the cartilage anlagen (preexisting cartilage)
30
How are endochondarl bone then formed?
Hypertrophic cartilage w high-level VGF expression wrap around middle of cartilage to form bone collar
31
What types of bone are endochondral?
long bones
32
Cell type of cartilage:
chondrocyte
33
precursors for clasts:
monocyte/mac origin
34
TF? Blasts can become cytes or clasts.
T
35
Cells that synthesize matrix:
cytes
36
TF's are aka:
nuclear proteins
37
TF? Each TF contain only one DNA binding site.
F. 1+
38
What are blasts and chondrocytes derived from?
mesenchymal precursor
39
These cells differentiate into chondrocytes:
mesenchymal cells
40
How does endochondral bone formation begin:
mesenchymal cells differentiate into chondrocytes
41
BPM sf:
bone morphogenic protein
42
Fxn of BMP:
act on mesenchymal stem cells to regulate differentiation
43
These all have important roles in commitment/ maintenance of chondrocyte phenotype:
Sox9, L-Sox-5 and Sox-6
44
These TFs are both require for blastic differentiation:
Run-2+ Osx-
45
Which expression starts first, Runx-2 or Osx?
Runx-2
46
These TFs downregulate Runx-2 activity
Twist famiiy
47
TFs that act on mesenchymal cell to differentiate to pre-chondrogenic cells:
BMPs and FGFs
48
TFs that act pre-chondrogenic cells to differentiate to early chondrocyte:
BMPs, FGFs, Wnts, Sox9, Sox5L, Sox6, B-catenin/TCF/LEF
49
TF's that downregulate differentiation from columnar chondrocyte to hypertrophic chondrocyte:
BMPs, PTHrP
50
TF's that upregulate differentiation from columnar chondrocyte to hypertrophic chondrocyte:
Runx2/3, Dlx5/6
51
Downregulates Runx2:
Twist 1,2
52
Upregulates differentiation from mesenchymal stem cell to pero-osteoblast:
Ihh, Runx 2
53
TFs that upregulate differentiation from pre-osteoblasts to osteoblast:
Osx, B-catenin, TCF, LEF
54
B-catenin, TCF, LEF upregulate these 2 differentiations:
pre-osteoblasts to osteoblast, pre-chondrogenic to early chondrocyte:
55
2 differentiations Runx2 upregulate:
columnar chondrocyte to hypertrophic chondrocyte, mesenchymal to pre-osteoblasts
56
TF regulating differentiation of mesenchymal stem cells to undergo mesenchymal condensation:
Sox9
57
These regulate transition from mesenchymal condensation chondrocytes:
Sox 5, 6, and 9
58
2 TFs that control blastic differentiation:
Runx2
59
What Positively controls maturation of chondrocytes to hypertrophy:
Runx2
60
What negatively controls maturation of chondrocytes to hypertrophy:
Sox 9
61
TF that has a role in both chondrocytic and osteoblastic differentiation:
Runx2
62
TF that provides specificity in osteoblastic differentiation:
Osterix
63
The only 2 TF leading from mesenchymal condensation in 2 steps to osteocytes:
Runx 2, Osterix
64
TF red for osteogenesis:
Runx2
65
Where is Runx 2 expressed?
mesoderm and osteoblast precursor cells
66
Mutation of Runx2 in animal models:
no binding to DNA: skeletal abnormalities (cleidocranial dysplasia)
67
TF needed or mesenchymal cells to diff to biopotential cells:
Ihh
68
TFs that upregulate dif of biopotential cells to preosteoblasts:
Wnt/B-catenin , Runx2
69
TFs that upregulate diff of preosteoblasts to osteoblasts:
Runx2
70
Main TF in the regulation of osteoblast differentiation and proliferation during bone formation:
Osx and Wnt/B-catenin
71
TF that initiates endochondral ossification:
Ihh
72
Runx2 expressing biopotential progenitor cells an differentiate into:
either osteoblasts or chondrocytes
73
TF that can inhibit the action of Wnt/B-catenin in the differentiation of osteoblast::
Osx
74
What does the inhibition of Wnt/B-catenin lead to?
inhibition of osteoblast proliferation
75
Col1a and ALP are markers of these cells:
biopotential cells, preosteoblasts and osteoblasts (low in bio, high in other 2)
76
Identifying markers of osteoblasts:
Osx, Bsp, OC
77
Bsp sf:
bone sialoprotein
78
Where can Bsp be found?
ecm protein
79
TF? 1 signaling pwy controls TF in osteoblast.
F. multiple
80
Pwys that control TF's in osteoblasts:
Ihh, glucocorticoids, Vit D, Wnt, Estrogens, PTH, TGFB, BPM2, FGF
81
regulate proliferation and differentiation of ostebloasts (usually a reciprocal relationship between these 2)
Wnt/ B-catenin
82
Cells slow/ speed in differentiation as they move toward differentiation:
slow
83
These all act directly on Runx2 in osteoblast differentiation:
Ihh, glucocorticoids, B-Catenin, estrogen receptor, MAPK, Smads, FGF-R
84
Fxn of BMP-R in osteoblast differentiation:
acts on both Smads and MAPK which both act directly on Runx2
85
These act on TGFb-R, PTH-R, and ER respectively:
TGFB, PTH, Estrogens
86
These all act directly on osteoblast gene differentiation:
B-catenin, Runx2, glucocorticoids, VDR
87
What acts on VDR, leading to an influence on osteoblast gene differentiation directly thereafter?
Vit D
88
Do blasts have PTH receptors?
yes
89
Collagen levels increase/dec as cells differentiate:
osteoblasts
90
Fxn of organic matrix of bone:
support and regulating the solid, inorganic C-P mineral phase of bone
91
Predominant component of organic matrix of bone;
collagen, 95%, the rest are non-collagenous/ plasma proteins
92
Cells that produce bone matrix:
osteoblasts
93
Principle collagen type in mineralized bone:
1
94
Collagen types that form heterotypic fiber bundles:
1 and 5
95
What provides the basic structural integrity of CT in alveolar bone?
heterotypic fiber bundles made of Type 1 and 5 collagen
96
Main producer of Type 3 collagen:
fibroblasts
97
When is Type 3 collagen formed?
in formation of PDL
98
Possible fxn of Type 12 collagen:
mechanical strength
99
Collagen types in alveolar bone:
Type 1, 3, 12
100
Common marker for alveolar bone:
Type 1 collagen
101
Spaces where bone mineralization can occur
: in and between the collagen fibers
102
What allows or unique deposition of mineral bw and within fibrils?
spatial distribution of collagen fibrils
103
Shape of mature collagen:
triple helix
104
Collagen triple helices form from:
nanoscale microfibrils which act as templates for the crystallization of HA nanocrystals
105
The cells become bone-forming osteoblasts after signals from bone-specific proteins in the matrix:
undifferentiated bone-marrow stem cells that recognize collagen matrix
106
What controls the chemotactic agent for sphingolin and allow migration of bone forming blasts to area
collagen fibrils
107
Flow chart, progression from collagen triple helix to bone:
CTH, HA crystals + bone-marrow stem cells, bone forming osteoblast cells, bone
108
Bone Resorption markers:
pyridinium cross-link collagen peptide fragments
109
Bone formation markers:
Type-1 procollagen propeptides
110
These are pyridinium cross-link collagen peptide fragments:
serum C-terminal telopeptide (ICTP), urine C-terminal telopeptide (Ctx), urine N-termianl telopeptide (NTx)
111
These are Type-1 procollagen propeptides:
C-terminal propeptide fragments (P1CP), N-terminal propeptide fragments (PINP)
112
These exposed when Type I collagen is broken down:
telopeptides
113
serum ICTP is:
serum C-terminal telopeptide
114
Elevated levels of these can be found in pts w osteoporosis, RA, paget' disease and hyperparathyroidism:
serum ICTP and other pyridinoline X-links correlated w bone resorptive rate
115
This can be used as a prognostic indicator in several metastatic bone tumors such as myeloma, prostate, lung and breast cancers:
Serum ICTP levels
116
Dec in pyridinoline X-lins have been demonstrated in these pts:
postmenopausal osteoporotic subjects after bisphosphonate or estrogen therapy
117
This may be a diagnostic marker of PDD:
GCF ICTP levels
118
ICTP levels are strongly correlated w :
Cx parameters of perio tissue destruction
119
Strong or weak connection bw elevated ICTP levels and implant failure?
strong
120
osteocalcin is aka:
Bone GLA-protein
121
osteocalcin:
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
TF? Vit K dependent protein is a clotting protein.
F
123
TF? Osteocalcin is directly related to initiation of mineralization.
F
124
Fxns of osteocalcin:
regulation of mineralization or bone turnover, chemoattractant, recruiting clasts to resorptive sites, marker to asses remodelling/bone formation in systemic bones
125
Fxn of osteocalcin in dentistry:
Level in GCF to monitor tooth movement in ortho, bone-specific marker of bone turnover but not as predictive indicator of PDD
126
This triggers the production o insulin by B cells:
osteocalcin
127
Why might osteocalcin be a tx or Type II diabetes?
signals fat cells to release adiponectin which inc insulin sensitivity, possible bone, fat cell communication
128
Insulin signaling in bone favors whole body glucose homeostasis by:
activating osteocalcin
129
Insulin signalling pwy to bone:
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
Bone has properties of an endo/exo crine organ:
endocrine, suggests osteocalcin could be a hormone
131
Accounts for 15% of noncollagenous ECM proteins:
Osteonectin
132
Is osteonectin present in CT?
yes, but 104X higher in bone
133
Fxn of osteonectin:
unknown
134
osteonectin has high affinities for:
collagen, HA
135
When do animal studies suggest osteonectin is formed:
once woven bone matures
136
This may serve as a potentiatior for and marker o flate bone formation/ maturity:
osteonectin
137
What has osteonectin be localized to on mRNA during fracture healing?
osteoblasts and hypertrophic chondrocytes
138
Role of GF's during bone repair:
Regulation of cell proliferation, chemotaxis, differentiation, matrix synthesis
139
Bone GF's are conc here:
in matrix
140
When are bone GF"s released?
during resorption
141
29 bone GF's:
TGFB, VEGF, BMPs 1-15, FGF 1-9, PDGF A, B, AB
142
GF that may have a role in modulated guided tissue regenerative therapy:
PDGF, can migrate to defect and fix
143
PDGF has a potent chemotactic and mitogenic effect on:
PDL fibroblasts
144
Scaffold to keep PDGF in place at site of bone repair:
Tricalcium phosphate carrier
145
PDGF can stimulate the growth of both:
bone and PDL
146
GF enhanced matrix is used to repair these perio defects:
inrabony/ furcation defect, gingival recession assoc w perio defects
147
What is the matrix component of GEM?
Beta-TCP
148
MOA is osseous wound:
brings precursor cells to defect area
149
mitogenesis is aka:
proliferation
150
GEF is made of:
bioactive protein rhPDGF, highly purified recombinant human PDGF and osteoconductive matrix B-TCP
151
GEF stimulates this cell of the periodontium the most:
fibroblast, then perivasicular cells
152
Cells stimulated by PDGF in the periodontium:
Fibroblasts, perivasicular cells, endothelial cells, osteoblasts, cementoblasts
153
Steps to using GEM:
soak B-TCP scaffold in fhPDGF-BB for 10m, debride defect, fill w GEM to alveolar crest
154
How long doe it take for release of rhPDGF-BB after placement of GEM:
minutes
155
GEM tx with B-TCP scaffold in fhPDGF-BB leads to replacement of these structures:
new alveolar bone, PDL, cementum
156
Will B-TCP alone lead to bone regeneration?
yes, not much less than w PDGF
157
Which provides more bone fill, B-TCP alone or that with PDGF?
w PDGF
158
FGF-2 stimulates:
perio tissue regeneration & clinical attachment level, bone regeneration
159
What is rhBMP-2 used for?
bone grafting
160
MOA of rhBMP-2:
implantation, chemotaxis, proliferation, differentiation, bone formation and Angiogenesis, Remodeling, normal trabecular bone
161
Cells that come to implantation site after rhBMP-2 placement:
mesenchymal stem cell, other bone forming cells
162
When do the cells multiply after rhBMP-2 placement?
before differentiation
163
This can enhance surgical soft and hard tissue wound healing:
platelet-rich plasm
164
Source of PRP:
autologous source of PDGF
165
GF"s are produced by:
blasts and platelets
166
Major growth factors present in PRP:
PDGF (AA, BB, AB), TGF-B, EGF, IGF-1
167
What's needed for the therapeutic effect of PRP?
concentration of platelets, 40-500%inc, 1million/ microliter in 5ml
168
Volume of blood typically needed from a pt for an oral bony defect:
20-60mL
169
Disadv of PRP use:
need to activate platelets, usually w thrombin or CaCl2, variability in platelet conc, disagreement as to usefulness of PRP
170
Cx proc in which PRP has been successful:
infrabony defects, inflammatory lesion, mucogingival proc, 3rd molar extraction healing, osseointegration in implant placement
