Oral Tissues, Osteoblasts, Osteocytes and Osteoclasts Flashcards
Which growth factor in osteoclast differentiation acts between CFU-M and the formation of the monocyte?
M-CSF
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?
osteoclasts
What does OPG do?
inhibits the process of osteoclast differentiation
Are osteoclasts derived from the same origin as osteocytes and osteoblasts?
NO
What is a natural inhibitor of mineralization in the body?
PPi
What cells control the responses of bone cells in regards to their mechanical load?
osteocytes
What cells make up over 90% of all bone cells?
osteocytes
What are the growth factors regulating osteoblast differentiation?
BMPs** TGF-beta WNT/B-catenin** Hedgehog IGF-1 PTH and PTHrP FGFs Notch pathway
What anabolic agent used in the treatment of osteoporosis stimulates bone formation, partly through the inhibition of sclerostin?
PTH 1-84
Teriparitide
Which growth factor in osteoclast differentiation acts between the monocyte and the mononucleated/prefusion osteoclast?
M-CSF
RANKL
What do mesenchymal progenitors give rise to?
myocytes
adipocytes
hypertrophic chondrocytes
osteoblasts
Which cells are embedded within the mineralized bone matrix?
osteocytes
Normally, estrogen is inhibiting ____ bone resorption.
osteoclast
____ are associated with mortality rates of up to 20-24% in the first year.
Hip fractures
___ consists of all the matrix proteins that these cells produce, particularly Type I collagen.
osteoid
Mechanosensory capabilities, control of bone resorption and formation, regulation of mineralization, and regulation of mineral homeostasis (Ca, Ph) are all functions of?
osteocytes
Why is the osteocyte a key target cell for the development of new treatments for diseases of bone loss and bone growth?
because of its very specific use and inclusion of sclerostin in their pathways
What are the osteoclast marker protein pumps?
carbonic anhydrase
vacuolar-type ATPase
What does cathepsin K do?
digests matrix proteins
What channel in a mature resorbing osteoclast maintains the charge neutrality?
Cl (chloride) channel
In _____, bone formation can’t keep up with bone destruction.
osteoporosis
What are the 3 major mutations associated with osteopetrosis?
- mutations in a3 subunit of vacuolar H+ ATPase
- mutations in Cl channel in osteoclast
- cathepsin K mutations
What marker would you find in a matured, late osteocyte?
SOST
What enzyme is indicative of an osteoblast?
alkaline phosphatase
What pathway is important in determining bone mass?
Wnt/B-catenin
Osteoclasts are derived from the same precursors as ___, which is the ___ lineage.
macrophages; hematopoietic
Which transcriptional regulator drives the terminal differentiation of osteoblasts into osteocytes, lining cells, and apoptotic cells?
B-catenin
Which two transcription factors are imperative for osteoblast formation and differentiation?
Runx2
Osterix
What enzyme that is active in a mature, resorbing osteoclast generates the protons needed to create an acidic pH?
carbonic anhydrase II (CAII)
At what stage of osteoclast differentiation are NFATc1, C-fos, and NFKB acting at?
the mononucleated (pre-fusion) osteoclast stage
Activating and inactivating mutations of Lrp5 lead to ___ and ___ bone mass, respectively.
high; low
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
What is the process called that dissolves and repairs bone through osteoclasts and osteoblasts in equlibrium?
bone remodeling process
Which growth factor allows the progression of the macrophage precursors into monocytes?
M-CSF
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
What would OPG prevent the progression of?
maturation of a fused and differentiated osteoclast by preventing the formation of its precursors
Why has hormone replacement therapy been replaced by SERMs?
because SERMs do not have harmful side effects on the uterus and breasts
What are some early osteocyte markers?
E11/gp/podoplanin
DMP1
MEPE
PHEX
____ is an antibody against RANKL and inhibits osteoclast formation.
Denosumab
If you increase your Wnt/B-catenin activation, then ___ bone mass results.
high
What ligand promotes the fusion of the osteoclast in the osteoclast differentiation pathway?
RANKL
The reduced activities of what can lead to hypophosphatasia?
alkaline phosphatase
Which transcriptional regulators drive the differentiation of immature osteoblasts into mature osteoblasts?
Osterix
B-catenin
What classification of osteoporosis treatment are PTH 1-84, Teriparitide, and anti-sclerostin antibodies?
anabolic agents
What are the 3 transcription factors that regulate the prefusion osteoclasts during their differentiation?
NFATc1
C-fos
NFKB
What marker is highly expressed in mature osteocytes, cementocytes, and odontoblasts?
sclerostin (SOST)
___ is required for osteoclast fusion and differentiation.
RANKL
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
What is a late osteocyte marker?
Sclerostin (SOST)
_____ plays an important role in mineralization of bone.
Alkaline phosphatase
What is the master transcription factor of osteoclast formation?
NFATc1
Rank osteoblasts, osteoclasts, and osteocytes from shortest lifespan to longest lifespan.
osteoclasts»_space; osteoblasts»_space; osteocytes
Which transcriptional regulators drive the differentiation of osteochondrogenic precursors into immature osteoblasts?
Runx2
B-catenin
____ express proteins that act as proton pumps to generate H+ ions to reduce pH and dissolve mineral.
Osteoclasts
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
Which cells are responsible for bone formation and are located on the surface of the bone?
osteoblasts