Physiology of Bone Flashcards
What is mainly found in the organic portion of the ECM in bone?
collagen
What organic component in the ECM of bone aids in hydroxyl apatite crystallization and binds calcium?
Osteonectin and osteocalcin
What organic components of the ECM of bone binds growth factors?
Proteoglycans
What organic components of the ECM in bone mediate osteoclast adhesion to bone surface (bind osteoclast integrins)
Sialoproteins, osteopontins, and thrombospondin
What are the main inorganic components of the ECM of bone?
inorganic hydroxyapatites or mineral salts, primarily calcium phosphate
What functions to pack tightly, contributing to the hardness and ability to resist compression?
the inorganic components
What is the function of osteogenic cells?
develop into osteoblasts
Where are osteogenic cells located?
in the deep layers of the periosteum and the marrow
What is the function of osteoblasts?
Bone formation
Where are osteoblasts found?
in growing portions of bone, including periosteum and endosteum
what is the function of osteocytes
maintain mineral concentration of matrix
where are osteocytes found?
entrapped in matrix
what is the function of osteoclasts?
bone resorption
where are osteoclasts found?
bone surfaces and site of old or injured bone matrix
Which bone cell type is cuboidal shaped?
osteoblast
which bone cell type directly regulates bone matrix synthesis and mineralization?
osteoblasts
How doe osteoblasts indirectly control bone resorption?
Through release of paracrine factors that regulate osteoclasts (RANKL/OPG)
What do osteoblasts eventually become?
osteocytes
Which bone cell can initiate apoptosis?
Osteoblasts
Which bone cell type is the terminally differentiated osteoblast?
Osteocytes
Where do osteocytes become trapped?
Within the newly deposited bone matrix
How do osteocytes respond to mechanical loading?
by releasing paracrine factors
Which bone cell secretes acid and lytic enzymes?
Osteoclasts
Which bone cells are multinucleated and are derived from mononuclear cells in the bone marrow?
Osteoclasts
What stimulates the proliferation and differentiation of osteoblasts and bone formation?
TGF-B
What increases OPG production?
TGF-B
What is a potent inducer of osteoblasts and bone formation?
Bone Morphogenic Proteins (BMPs)
How is BMP used clinically?
rhBMP-2 is used in fracture healing and spinal fusions
What is secreted by osteoblasts, binds RANKL, and prevents osteoclast activation?
Osteoprotegerin (OPG)
What increases proliferation of osteoblasts and enhances callus formation during fracture repair?
Fibroblast Growth Factors (FGFs)
What does FGF-2 stimulate?
Angiogenesis during fracture repair
What is stimulated by growth hormone and increases bone collagen matrix synthesis and inhibits degradation?
Insulin-like growth factors (IGFs)
What increases collagen synthesis?
Platelet Derived growth factor (PDGF)
What activates osteoclasts for bone resorption?
RANKL
What secretes RANKL?
osteoblasts
What is RANKL regulated by?
OPG
What stimulates bone resorption and which is the most potent?
Interleukins; IL-1 is the most potent
What is IL-1 expression decreased by?
Estrogen
What signals release of PTH?
Falling blood calcium levels (hypocalcemia)
What does PTH signal?
Signals osteoclasts to degrade bone matrix and release Ca into the blood
Limited movement would result in which type of fracture healing?
indirect bone healing
No movement would result in which type of fracture healing?
direct bone healing
When is the inflammatory phase of indirect (secondary) fracture healing?
~1 week
When is the soft callus formation in indirect (secondary) fracture healing?
weeks 2-3
When is the hard callus formation in indirect (secondary) fracture healing?
weeks 4-12
When does remodeling of bone occur in indirect (secondary) fracture healing?
years
If there is direct contact between fragment ends, what forms?
lamellar bone
If there is a gap of 200-500 nm, what forms?
woven bone and then eventually lamellar bone
If there is a gap of 500 nm what occurs?
Indirect healing
What inhibits osteoclast activity and induces osteoclast apoptosis?
bisphosphonates
What is a monoclonal antibody against RANKL?
Denosumab
What induces osteoblast proliferation and activity for increased bone matrix production?
BMP-2
What effect do thyroid hormones have on bone metabolism?
They (thyroxine and triiodothyronine) stimulate osteoclastic bone resorption
What effect do glucocorticoids have on bone metabolism?
they inhibit calcium absorption from gut, which causes increased PTH and therefore increased orthoclastic bone resorption
What does intermittent exposure to PTH stimulate?
osteoblasts and increased bone formation
What does more chronic exposure of pathological levels of PTH stimulate?
osteoclasts to release calcium, which can lean to hypercalcemia
What effect does growth hormone have on bone metabolism?
It increases callus formation and fracture strength by stimulating osteoblasts
