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
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
3
Q
What does OPG do?
A
inhibits the process of osteoclast differentiation
4
Q
Are osteoclasts derived from the same origin as osteocytes and osteoblasts?
A
NO
5
Q
What is a natural inhibitor of mineralization in the body?
A
PPi
6
Q
What cells control the responses of bone cells in regards to their mechanical load?
A
osteocytes
7
Q
What cells make up over 90% of all bone cells?
A
osteocytes
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
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
10
Q
Which growth factor in osteoclast differentiation acts between the monocyte and the mononucleated/prefusion osteoclast?
A
M-CSF
RANKL
11
Q
What do mesenchymal progenitors give rise to?
A
myocytes
adipocytes
hypertrophic chondrocytes
osteoblasts
12
Q
Which cells are embedded within the mineralized bone matrix?
A
osteocytes
13
Q
Normally, estrogen is inhibiting ____ bone resorption.
A
osteoclast
14
Q
____ are associated with mortality rates of up to 20-24% in the first year.
A
Hip fractures
15
Q
___ consists of all the matrix proteins that these cells produce, particularly Type I collagen.
A
osteoid
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
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
18
Q
What are the osteoclast marker protein pumps?
A
carbonic anhydrase
vacuolar-type ATPase
19
Q
What does cathepsin K do?
A
digests matrix proteins
20
Q
What channel in a mature resorbing osteoclast maintains the charge neutrality?
A
Cl (chloride) channel
21
Q
In _____, bone formation can’t keep up with bone destruction.
A
osteoporosis
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
23
Q
What marker would you find in a matured, late osteocyte?
A
SOST
24
Q
What enzyme is indicative of an osteoblast?
A
alkaline phosphatase
25
What pathway is important in determining bone mass?
Wnt/B-catenin
26
Osteoclasts are derived from the same precursors as ___, which is the ___ lineage.
macrophages; hematopoietic
27
Which transcriptional regulator drives the terminal differentiation of osteoblasts into osteocytes, lining cells, and apoptotic cells?
B-catenin
28
Which two transcription factors are imperative for osteoblast formation and differentiation?
Runx2
| Osterix
29
What enzyme that is active in a mature, resorbing osteoclast generates the protons needed to create an acidic pH?
carbonic anhydrase II (CAII)
30
At what stage of osteoclast differentiation are NFATc1, C-fos, and NFKB acting at?
the mononucleated (pre-fusion) osteoclast stage
31
Activating and inactivating mutations of Lrp5 lead to ___ and ___ bone mass, respectively.
high; low
32
In mutations where sclerostin is ___, a high bone mass phenotype is expressed; when sclerostin is ___, a low bone mass phenotype is expressed.
absent/null; overexpressed/gain-of-function
33
What is the process called that dissolves and repairs bone through osteoclasts and osteoblasts in equlibrium?
bone remodeling process
34
Which growth factor allows the progression of the macrophage precursors into monocytes?
M-CSF
35
What does the mutation that causes Stone Man syndrome, BMP type 1, cause in regards to ligands?
it causes mild constitutive action of the ligand, allowing receptor activation without the ligand actually being present
36
What would OPG prevent the progression of?
maturation of a fused and differentiated osteoclast by preventing the formation of its precursors
37
Why has hormone replacement therapy been replaced by SERMs?
because SERMs do not have harmful side effects on the uterus and breasts
38
What are some early osteocyte markers?
E11/gp/podoplanin
DMP1
MEPE
PHEX
39
____ is an antibody against RANKL and inhibits osteoclast formation.
Denosumab
40
If you increase your Wnt/B-catenin activation, then ___ bone mass results.
high
41
What ligand promotes the fusion of the osteoclast in the osteoclast differentiation pathway?
RANKL
42
The reduced activities of what can lead to hypophosphatasia?
alkaline phosphatase
43
Which transcriptional regulators drive the differentiation of immature osteoblasts into mature osteoblasts?
Osterix
| B-catenin
44
What classification of osteoporosis treatment are PTH 1-84, Teriparitide, and anti-sclerostin antibodies?
anabolic agents
45
What are the 3 transcription factors that regulate the prefusion osteoclasts during their differentiation?
NFATc1
C-fos
NFKB
46
What marker is highly expressed in mature osteocytes, cementocytes, and odontoblasts?
sclerostin (SOST)
47
___ is required for osteoclast fusion and differentiation.
RANKL
48
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.
osteopetrosis
49
What is a late osteocyte marker?
Sclerostin (SOST)
50
_____ plays an important role in mineralization of bone.
Alkaline phosphatase
51
What is the master transcription factor of osteoclast formation?
NFATc1
52
Rank osteoblasts, osteoclasts, and osteocytes from shortest lifespan to longest lifespan.
osteoclasts >> osteoblasts >> osteocytes
53
Which transcriptional regulators drive the differentiation of osteochondrogenic precursors into immature osteoblasts?
Runx2
| B-catenin
54
____ express proteins that act as proton pumps to generate H+ ions to reduce pH and dissolve mineral.
Osteoclasts
55
In mutations where sclerostin is ___, a high bone mass phenotype is expressed; when sclerostin is ___, a low bone mass phenotype is expressed.
absent/null; overexpressed/gain-of-function
56
Which cells are responsible for bone formation and are located on the surface of the bone?
osteoblasts
57
What are RANKL and M-CSF produced by?
osteoblasts and osteocytes
58
What is the role of the Cl and HCO3 exchanger?
it removes excess bicarbonate
59
What is fibrodysplasia ossificans progressiva, or "Stone Man syndrome," characterized by?
heterotopic bone formation that fuses joints, ribs and other parts of the body with new bone
60
____ is the loss of bone mass, often associated with menopause or aging.
Osteoporosis
61
Osteoblasts, chondrocytes, myoblasts, and adipocytes were all differentiated from a common _____.
mesenchymal precursor
62
What proteins promote the differentiation from early progenitor cells in osteoblast differentiation?
BMPs
63
At what stage of osteoclast differentiation is RANKL working at?
pre- and post-formation of the multinucleated osteoclast
64
What anti-resorptive binds to hydroxyapatite and inhibits the activity of osteoclasts by inhibiting the melavonate pathway?
bisphosphonates
65
What happens to GSK-3B when Wnt is NOT bound to the receptor?
it tags B-catenin to be degraded so it cannot act as a transcription factor
66
What happens if the transcriptional regulator Runx2 stays on too long in osteoblast differentiation?
it can inhibit maturation and terminal differentiation
67
Bisphosphonates have a high affinity for ____.
hydroxyapatite
68
Which enzyme is an osteoclast marker protein?
TRAP (tartrate resistant acid phosphatase)
69
Can osteoclasts remove ECM proteins, too?
YES - express proteases for removing ECM proteins like collagen
70
What measure constitutes osteoporosis?
a patient having a bone mass density >2.5 standard deviations below the average
71
Sclerostin inhibits ___ to shut down the activating mutation that leads to high bone mass.
Wnt binding to its receptor
72
What are the two major clinical forms of osteopetrosis?
= autosomal dominant - adult type - few symptoms
| = autosomal recessive - infantile type - typically fatal
73
The severity of hypophosphatasia varies due to the relative loss of ___.
alkaline phosphatase
74
___ cells are quiescent cells that lie on top of the new bone built up by the osteoblasts.
Lining
75
Human mutations in SP7 (Osterix) is associated with what disease?
osteogenesis imperfecta XII
76
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?
Cleidocranial dysplasia
77
___ is a master transcription factor for bone.
Runx2
78
What is the cause of osteopetrosis?
impaired osteoclast function (either from failed formation OR impaired function)
79
Why would antibodies to sclerostin be a potentially beneficial treatment for patients with osteoporosis?
because inhibiting sclerostin would remove the "brake" of the Wnt/B-catenin pathway and allow for more bone to be made
80
What happens when Wnt IS bound to the receptor?
GSK-3B is phosphorylated, which releases B-catenin and allows it to travel to the nucleus and activate gene transcription
81
How long do osteocytes live?
decades
82
Which key signaling pathway is present between the mesenchymal stem cell and osteochondrogenic precursors in the proliferation phase?
BMPs (2, 7)
83
What does an osteoclast need to do?
- 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
What is it called when bones forms inappropriately in soft tissues?
heterotopic bone formation
85
Which type of cell in the bone is multinucleated and is responsible for removing bone?
osteoclasts
86
In bony remodeling, as osteclasts resorb bone, they release ____ that attract osteoblasts.
chemotactic factors
87
What ECM proteins are indicative of an osteoblast?
Type I collagen
osteopontin
osteocalcin
bone sialoprotein (BSP)
88
When Osterix is knocked out, does bone eventually form?
NO - the cartilage is mineralized but does not progress to bone
89
What classification of osteoporosis treatment are bisphosphonates, hormone replacement therapy, selective estrogen receptor modulators, denosumab, and cathepsin K inhibitors?
anti-resorptives
90
What is the natural inhibitor of RANKL?
OPG
91
Which osteoblast genes does Osterix control the expression of?
Type I collagen
Osteocalcin
Osteopontin
92
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?
RANKL
93
Can the WNT/B-catenin pathway inhibit osteoblast differentiation?
YES - if the signals are turned on too early
94
Are osteocytes terminally differentiated osteoblasts?
YES
95
Do osteocytes play a role in homeostasis?
YES - they play a role in the endocrine regulation of phosphate homeostasis
96
Which enzyme pumps the protons into the resorption lacuna to allow the osteoclast to dissolve the mineral?
vacuolar-type H+ ATPase pumps
97
What transcription factors are indicative of an osteoblast?
Runx2
| Osterix
98
What is BONJ attributed to?
the suppression of bone turnover occurred through the inhibition of osteoclast activity
99
What does the deletion of the SOST gene result in?
sclerostosis or Van Buchem's disease
100
Which key signaling pathway is present between the mature osteoblast and terminally differentiated cells?
WNT/B-catenin
101
What happens if the Runx2 gene is lacking?
cartilage fails to mineralize or bones may not form
102
___ mutations generally lead to reduced levels of a protein, generally.
Missense
103
Mutations in what protein causes Stone Man syndrome?
BMP type I receptor
104
Would bisphosphonates have an effect on orthodontic tooth movement?
YES
105
Worldwide, how many women and men will experience osteoporotic fractures?
1 in 3 women
| 1 in 5 men
106
Which key signaling pathway is present between the immature osteoblast and mature osteoblast in the maturation phase?
WNT/B-catenin
107
What is the primary transcription factor in osteocytes?
Mef2c
108
How do osteoclasts attach to the bone surface?
through aB3 integrins
109
Which transcriptional regulator is important in the proliferation, maturation, AND terminal differentiation of osteoblasts?
B-catenin
110
Osteoblasts originate from ____ cells.
mesenchymal stem
111
What bone cells produce large amounts of ECM proteins, such as type I collagen, that eventually mineralizes?
osteoblasts
112
What does the knockout of specific BMPs lead to?
skeletal defects
113
Do we see osteoclast activity in normal bone growth?
YES
114
What are some osteoclast marker protein receptors?
RANK (for RANKL)
C-fms (for M-CSF)
calcitonin receptor
integrin avB3
115
____ hydrolyzes pyrophosphate (PPi), a natural inhibitor of mineralization, which increases local phosphate concentration and promotes mineralization.
Alkaline phosphatase
116
Alkaline phosphatase promotes ____.
mineralization
117
What are two osteoclast marker protein proteases?
cathepsin K
| MMP9, MMP13
118
What happens if the transcriptional regulator B-catenin appears too early in osteoblast differentiation?
it can actually inhibit the processes of proliferation
119
FGF23, DMP1, and PHEX are all genes important in ____.
phosphate homeostasis
120
____ prevent patients from losing further bone but do not build back the bone lost.
Anti-resorptives
121
What does M-CSF promote the proliferation and survival of?
osteoclast precursors
122
What drives osteoblast differentiation?
key transcriptional regulators that signal progression into next phase
123
Alkaline phosphatase is an enzyme highly expressed in ___ and ___.
osteoblasts; odontoblasts
124
Which primary transcription factor regulates the mononucleated (prefusion) osteoclast in osteoclast differentiation?
NFATc1
125
What would a histological section of osteonecrosis look like? What wouldn't be present?
necrotic bone with empty osteocyte lacunae; osteocytes
126
What pH is needed to dissolve bone mineral in the osteoclast's resorption bays?
4.5
127
_____ proteins promote differentiation from early osteoprogenitor cells in osteoblast differentiation.
Bone morphogenic proteins (BMPs)
128
The loss of ____ leads to increased bone resorption.
estrogen
129
In humans, mutations in the ____ gene is associated with hypophosphatasia.
alkaline phosphatase
130
Osteoblasts and osteocytes produce RANKL receptors on their cell surfaces and secrete M-CSF. How do these two factors promote proliferation of osteoclast precursors?
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
___ is a negative regulator of bone formation, in that it acts as a "brake" to limit the formation of bone.
Sclerostin (SOST)
132
In osteopetrosis, why must hematopoiesis often migrate to other locations to maintain function?
the marrow cavities shrink and become very narrow
133
What are BMPs required for?
skeletal development and maintenance of adult bone homeostasis
134
___ are the main producer of Type I collagen in bone.
Osteoblasts
135
___ is a rare, heritable rickets or osteomalacia due to reduced activity of alkaline phosphatase.
Hypophosphatasia
136
___ flatten to become a lining cell.
Osteoblasts
137
____ have proven to be useful in treating patients with cancer who have high serum calcium levels.
Bisphosphonates
138
What does sclerostin (SOST) do to the Wnt/B-catenin pathway?
it shuts it down as to limit the excess formation of bone
139
What structure allows for the dissolution of bone?
the ruffled border of the osteoclast
140
Which key signaling pathway is present between the osteochondrogenic precursors and immature osteoblasts, entering the maturation phase?
WNT/B-catenin
141
Runx2 induces another transcription factor called ____, which is also critical for osteoblast differentiation.
Osterix
