090814 intro to bone Flashcards
what do osteoblasts differentiate from?
mesenchymal stem cells
RUNX2
transcription factor that’s expressed in all cells of the osteoblast lineage
also known as Cbfa-1
what do pre osteoblasts make?
low collagen type I and low alkaline phosphatase
alkaline phosphatase
breaks pyrophosphate to monophosphate
pyrophosphate inhibits mineralization, so you need alkaline phosphatase for mineralization
how can you differentiate mesenchymal stem cells, pre osteoblasts, osteoblasts, and mature osteoblasts/osteocytes?
from the genes they express
how do osteoclasts mature?
they need dual signaling :
1) MCSF (from the hematapoietic side)
2) RANK ligand (to activate the osteoclast specific pathway)–they need to communicate with osteoblasts
cortical bone and trabecular bone differences
80-90% of cortified bone’s volume is calcified, whereas 15-25% of trabecular bone’s volume is
cortical bone has mainly mechanical and protective fxn, whereas trabecular bone has mainly a metabolic fxn (calcium and phosphate)
cortical bone is 80% of bone, trabecular bone is 20%
histology: compact bone vs trabecular
compact and trabecular both are organized into lamellae (have same cells and same matrix elements)
trabecular bone has spaces in btwn trabeculae which hold bond marrow or adipose tissue
lamellae are organized how?
in different orientations
osteocytes are important for what role?
orchestrating bone turnover–they communicate with osteobl and ostecl that are at the surface of bone
ex–osteocytes express sclerostin, which inihibits maturation of osteoblasts
intramembranous ossification occurs for what bone?
calvaria
chondroblasts’ role in encochondral ossification
they clear away the dead apoptotic chondrocytes and the zone is replaced by osteoblasts
growth plates close ate what age?
different ages for different bones
bone remodeling in trabecular vs cortical bone
trabecular has 12 BRUs activated each minute; annual turnover rate is 25%
cortical has 3 BRUs activated each minute; annual turnover rate is 2-3%
remodeling cycle takes 4-6 months for both
diff btwn bone remodeling in cortical and cancellous remodeling
cortical has a moving Haversian system in which osteoclasts are leading it and right behind is the reversion zone, followed by osteoblasts
cancellous doesn’t have moving system. but has same components
how is bone remodeling like interstate construction?
10% remodeled at any given time
certain areas are remodeled more than others
digging up is fast; filling in is slow; rebuilding can take up to 6 months
which part of bone remodeling is the slowest
mineralization
what is used to measure mineralization rate of bone
double tetracycline labeling
structure of collagen fibers
composed of tropocollagen, which is composed of three pro alpha collagen chains
in fibers, you have offsets in lining of the fibers; also have spaces; repetitive structure; cross links within the fibers connect the components
cross links (within tropocollagen and from tropocollagen to neighboring tropocollagen) provide tensile strength
cross link composition is strong when
it is converted from enzymatic to aromatic form
aromatic form has pyridinoline and deoxypyridinoline
can use the aromatic cross links to measure bone resoption because they are specific for bone (antibodies bind in the test to them)
lamellar organization in different directions is important because?
then when you have stress, the strains can get deflected so you get micro or stress fractures instead of more serious injury
type I collagen composition
three stranded triple helix composed of two alpha1 chains, one alpha2 chain
osteogenesis imperfecta
defect in synthesis of usually collagen by osteoblasts
can result in bowing of bones, disability
COLIA1 G748C’s importance
a point mutation results in bent collagen fiber synthesis and thus bone matrix is weak
this is lethal–get breathing problems
osteomalacia
bone matrix is made normally but there isn’t enough minerals (environment doesn’t provide enough minerals-low vitamin D, low calcium etc)
the unminernalized portion of bone should normally just represent 5%
weak bones
how can you detect osteomalacia
villanueva stain
mineralized matrix is green
osteoid is orange–if you see thickened osteoid, not good
rickets
osteomalacia during growth
you see bowing of the legs
can get stress fractures
sclerosteosis
defective osteocytes
osteocytes are defective in sclerostin (sclerostin is made by mature osteoblasts and osteocytes–if mutated, bone thinks it is loaded all the time and you get increase in bone mass and possible nerve entrapment)
nerve entrapment can cause facial palsy and deafness
osteopetrosis
osteoclasts are unable to resorb bone during remodeling
problem you get is high bone density, but the bones are weak because they are disorganized (you need remodeling to occur in order to get structure)
second problem is you won’t have marrow space
paget’s disease
some places get remodeled more than others–but are incessantly remodeled. however, even though incessantly remodeled, they are poorly mineralized and weak
you see increase in markers of bone turnover
pain osseous bowing and enlargement neurologic symptoms labs predisposition to osteosarcoma
labs for paget’s disease show
increased serum alkaline phosphatase (blastic)
urinary hydroxyproline increased (lytic)
bone scan
shows where increased or decreased turnover of bone is occurring
