Intro to Bone Flashcards
what do osteoblasts differentiate from?
mesenchymal stem cells
what signals to RUNX2?
TGF, BMP, PTH, steroids, IGF, FGF, TNF
also WNT/B-Catenin
order of osteoblast differentiation
MSC –> pre-osteoblast –> osteoblast –> mature osteoblast
factors present @ pre-osteoblast
COL (low), AP (low), RUNX2
factors present @ osteoblast
COL (high), AP (high), OSX, OC, ON, RUNX2
factors present @ mature osteoblast
COL (high), AP (high), DMP, SOST, DKK1
how do osteocyte processes communicate?
gap junctions
factors inducing osteoclast development
MCSF, RANK-Ligand
different bone components? 2
cortical bone, trabecular bone. constituted from same cells & matrix elements
cortical bone structure/fxn
80-90% vol is calcifies. mechanical/protective fxn. little metabolism. always on outside of bones, surrounds trabecular bone. 80% of bone.
trabecular bone structure/fxn
15-25% of volume is calcified. mainly fulfills metabolic function. ~20% of bone.
compact bone histology
osteon (haversian system), concentric layers of lamellae around. empty spaces = lacunae
trabecular bone histology
yellow bone marrow (adipose), bone trabeculae are pink splotches
how do osteocytes signal to bone surface?
RANK-L signals to osteoclasts. Sclerostin inhibits growth of osteoblasts. sense mechanical force, direct where bone is deposited or absorbed.
endochondral ossification (zones from top to bottom/bone)
zone of reserve cartilage (farthest from bone); zone of proliferation; zone of hypertrophy and calcification; zone of retrogression & ossification; zone of resorption; bone matrix
remodeling cycle of trabecular or cancellous bone
12 BRUs/min, annual turnover 25%. accounts for 80% of turnover b/c higher surface:vol ratio. remodeling cycle = 4-6 mo.
remodeling cycle of cortical or compact bone
3 BRUs/min, 2-3% annual turnover. 20% of turnover, lower rate. less vascularity. 4-6 mo for remodeling cycle.
cortical remodeling (haversian) shape
cutting cone. matrix –> mineralized osteocytes. break down and resorb. (penis shaped, leading edge = head)
cancellous remodeling shape
no moving cylindrical structure. dip in thickness then gradually back up
what can you use to measure mineralization rate?
double tetracycline labeling. 2 days apart, bands show where it was deposited. measure distance between, divide by # days.
steps in fracture healing
- hematoma formation
- fibrocartilaginous callus formation (external callus, invaded by new blood vessels into spongy bone trabeculae)
- bony callus formation (bony callus of spongy bone, bulge @ fracture)
- bone remodeling
assembly of pro-alpha collagen and processing into tropocollagen
Type 1 collagen. pro-a chains to procollagen to tropocollagen. 3 strands, left-handed triple helix. starts @ C-terminus.
assembly of tropocollagen into fibers
regular repetitive array. crosslinks and fibrils. spaces = stripes on EM, regular banding pattern
collagen cross-links
less cross-linking = weaker. more = stronger.
which lysines give collagen a higher bond energy?
pyridinoline & deoxypyridinoline. mature collagen has higher tensile strength
hierarchal structure in human compact bone
collagen molecule –> collagen fibril –> collagen fibers –> aversion layer –> bone
cement lines purpose?
dissipate force. lamellar structure makes bones stronger.
osteogenesis imperfecta
defective synthesis of organic components of bone matrix. pathophys has to do with osteoblasts. point-mutation, modification of proline residues in T1 cell. defect in synthesis of ECM by osteoblast.
OI histo
COL1A1. bent fibrils. skeletal fragments. radigraphs: fractures, bowing
osteomalacia
passive. not enough mineralization. villaneuva strain. too much osteoid, thickened seams. can fix by fixing mineral balance.
rickett’s
not enough vitamin D. stress fractures at femoral neck common. bowed legs.
sclerosteosis
defective osteocytes. sclerostin mutation. increased bone mass, can cause nerve entrapment, overgrown bones. nerve entrapment leads to facial palsy, deafness. some mutations also cause syndactyly.
osteopetrosis
osteoclasts are unable to resorb bone during remodeling cycle. disorder of impaired resorption. high bone density but weak b/c disorganized. can lead to no space in marrow for hematopoesis.
osteopetrosis histology
paucity of marrow space, full of bone tissue. woven bone, not regular lamellar appearance.
Paget’s disease
excessive remodeling in one place. bone is weak, disorganized, poorly mineralized. uncoupled remodeling. woven bone (lacks lamellar structure)
Paget’s disease clinical features + labs
pain, osseous bowing/enlargement. neurologic stx. predisposed to osteosarcoma.
labs: serum AP increased (blastic phase); urinary hydroxyproline increased (lytic phase); most cases are mixed lytic & blastic.
