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