osteoblasts, osteocytes
Early-Dmp1 E11 late-MEPE PHEX sclerostin
what are markers of early osteocytes? markers of late osteocytes?
anti-resorptive agent
a drug that inhibits bone resorption
BMPs and Wnts through B-catenin signaling pathway
What are the growth factor signaling pathways important for osteoblast differentiation?
RANKL M-CSF
What are the two important regulating factors for osteoclast formation?
TRAP
What enzyme is characteristic of osteoclasts?
OPG
___________ inhibits RANKL
NFATc1 c-fos NFKB
___________ is the master transcription factor that controls osteoclast differentiation. ___ and ______ are important as well.
osterix
_____________ is a key transcription factor for osteoblast differentiation that is downstream of Runx2
alkaline phosphatase pyrophosphate
______________________ is a marker gene for osteoblasts. This enzyme plays an important role in bone mineralization by hydrolyzing _______________. This increases the local concentration of phosphate and promotes mineralization.
Lrp5
Activating mutations of ________ lead to increased wnt/b-catenin signaling and result in a high bone mass phenotype
ACVR1
Activating mutations of the ________ gene, which encodes a receptor for BMPs results in fibrodysplasia ossificans progressive, in which bony plates form in inappropriate sites, restricting movement of the skeleton
Osteogenesis imperfecta type XII
Human mutations in osterix are associated with _____________.
hyperphosphatasia
Humans lacking alkaline phosphatase (TNSALP) show impaired mineralization and ______________
osteopetrosis
If osteoclast function is impaired, then will get _______________ or abnormally dense bones
osteonecrosis of the jaw
Inhibitors of bone resorption such as bone bisphosphonates, have been associated with _________________
RUNX2 (w/o doesn't mineralize) OSTERIX(w/o milder delayed mineralization)
Osteoblast differentiation is controlled by two key transcription factors: _____________ and ______________
mesenchymal hematopoietic precursors
Osteoblasts and osteocytes are _________ in origin and osteoclasts are derived from _______ via the macrophage/monocyte lineage.
alkaline phosphatase type 1 collagen osteonectin osteopontin bone sialoprotein
Osteoblasts express marker genes such as ________,_________,__________,___________, ______________
RANK C-fms TRAP MMP9 MMP13
Osteoclast marker genes include ____________, ________, ________, ________, ___________
alpha v beta 3 integrins carbonic anhydrase II
Osteoclasts attach via _____________ to form sealed zone. ____________ generates protons.
phosphate homeostasis
Osteocytes play an endocrine role in the regulation of _____________________
phosphate
Osteocytes regulate the activity of osteoblasts and osteoclasts and also regulate _________________ homeostasis.
AD=CLC7 chloride channels (CLCN7) AR=alpha 3 sununit of H+ ATPase (TCIRG1)
Osteopetrosis can be autosomal dominant or recessive. -What accounts for the majority of AD? -What causes the majority of AR?
type I collagen osteocalcin osteonectin osteopontin
Osterix controls the expression of osteoblast genes: _________, ___________, _______________, __________________
inhibitor bone anabolic drugs
Sclerostin is highly expressed by osteocytes and acts as an ____________ of bone formation by inhibiting wnt/beta-catenin signaling; is a promising target for _________________.
heterotrophic bone formation
bone that forms in the wrong place
osteonecrotic bone
bone that is dead and does not have viable osteocytes
osteoblast
cell in bone that is responsible for forming new bone; mesenchymal in origin
mechanosensor
cell that can sense mechanical input
osteocyte
cell that is embedded in mineralized bone matrix; it is derived from an osteoblast which has become entrapped in mineralized bone
osteoclast
cells in bone responsible for resorbing bone; is multinucleated and of hematopoietic in origin (macrophage/monocyte lineage)
Fibrodysplasia ossificans progressive
disease due to mutation in BMP type 1 receptor (ACVR1) that results in ectopic mineralization in non-skeletal soft tissues, leading to sheets of bone forming across the joints, restricting movement of the skeleton.
hypophosphatasia
disease of impaired mineralization due to mutation in the gene for alkaline phosphatase that results in reduced amounts or no alkaline phosphatase.
osteopetrosis
disease of impaired osteoclast function that leads to bones that are abnormally dense but brittle and prone to fracture; caused by mutations in genes for osteoclast resorption
osteoporosis
disease of low bone mass that occurs due to the inability of bone formation to keep up with bone resorption. Usually seen in post meno-pausal women and the old people
cleidocranial dysplasia
disease to mutations in the RUNX2 gene; patients have partly or completely missing clavicles and supernumerary teeth
sclerostosis and van buchem's
diseases due to mutations in the gene for sclerostin (SOST) that cause reduced amounts of sclerostin to be produced leading to increased bone mass
bone anabolic agent
drug that stimulates bone formation
bone remodeling
process by which mature bone is removed by osteoclasts and replaced with new bone by osteoblasts (no net gain)
bone modeling
process by which new bone is added; can lead to a net gain in bone