Intro to Bone

Question 1

what do osteoblasts differentiate from?

Answer 1

mesenchymal stem cells

Question 2

what signals to RUNX2?

Answer 2

TGF, BMP, PTH, steroids, IGF, FGF, TNF

also WNT/B-Catenin

Question 3

order of osteoblast differentiation

Answer 3

MSC –> pre-osteoblast –> osteoblast –> mature osteoblast

Question 4

factors present @ pre-osteoblast

Answer 4

COL (low), AP (low), RUNX2

Question 5

factors present @ osteoblast

Answer 5

COL (high), AP (high), OSX, OC, ON, RUNX2

Question 6

factors present @ mature osteoblast

Answer 6

COL (high), AP (high), DMP, SOST, DKK1

Question 7

how do osteocyte processes communicate?

Answer 7

gap junctions

Question 8

factors inducing osteoclast development

Answer 8

MCSF, RANK-Ligand

Question 9

different bone components? 2

Answer 9

cortical bone, trabecular bone. constituted from same cells & matrix elements

Question 10

cortical bone structure/fxn

Answer 10

80-90% vol is calcifies. mechanical/protective fxn. little metabolism. always on outside of bones, surrounds trabecular bone. 80% of bone.

Question 11

trabecular bone structure/fxn

Answer 11

15-25% of volume is calcified. mainly fulfills metabolic function. ~20% of bone.

Question 12

compact bone histology

Answer 12

osteon (haversian system), concentric layers of lamellae around. empty spaces = lacunae

Question 13

trabecular bone histology

Answer 13

yellow bone marrow (adipose), bone trabeculae are pink splotches

Question 14

how do osteocytes signal to bone surface?

Answer 14

RANK-L signals to osteoclasts. Sclerostin inhibits growth of osteoblasts. sense mechanical force, direct where bone is deposited or absorbed.

Question 15

endochondral ossification (zones from top to bottom/bone)

Answer 15

zone of reserve cartilage (farthest from bone); zone of proliferation; zone of hypertrophy and calcification; zone of retrogression & ossification; zone of resorption; bone matrix

Question 16

remodeling cycle of trabecular or cancellous bone

Answer 16

12 BRUs/min, annual turnover 25%. accounts for 80% of turnover b/c higher surface:vol ratio. remodeling cycle = 4-6 mo.

Question 17

remodeling cycle of cortical or compact bone

Answer 17

3 BRUs/min, 2-3% annual turnover. 20% of turnover, lower rate. less vascularity. 4-6 mo for remodeling cycle.

Question 18

cortical remodeling (haversian) shape

Answer 18

cutting cone. matrix –> mineralized osteocytes. break down and resorb. (penis shaped, leading edge = head)

Question 19

cancellous remodeling shape

Answer 19

no moving cylindrical structure. dip in thickness then gradually back up

Question 20

what can you use to measure mineralization rate?

Answer 20

double tetracycline labeling. 2 days apart, bands show where it was deposited. measure distance between, divide by # days.

Question 21

steps in fracture healing

Answer 21

1. hematoma formation
2. fibrocartilaginous callus formation (external callus, invaded by new blood vessels into spongy bone trabeculae)
3. bony callus formation (bony callus of spongy bone, bulge @ fracture)
4. bone remodeling

Question 22

assembly of pro-alpha collagen and processing into tropocollagen

Answer 22

Type 1 collagen. pro-a chains to procollagen to tropocollagen. 3 strands, left-handed triple helix. starts @ C-terminus.

Question 23

assembly of tropocollagen into fibers

Answer 23

regular repetitive array. crosslinks and fibrils. spaces = stripes on EM, regular banding pattern

Question 24

collagen cross-links

Answer 24

less cross-linking = weaker. more = stronger.

Question 25

which lysines give collagen a higher bond energy?

Answer 25

pyridinoline & deoxypyridinoline. mature collagen has higher tensile strength

Question 26

hierarchal structure in human compact bone

Answer 26

collagen molecule –> collagen fibril –> collagen fibers –> aversion layer –> bone

Question 27

cement lines purpose?

Answer 27

dissipate force. lamellar structure makes bones stronger.

Question 28

osteogenesis imperfecta

Answer 28

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.

Question 29

OI histo

Answer 29

COL1A1. bent fibrils. skeletal fragments. radigraphs: fractures, bowing

Question 30

osteomalacia

Answer 30

passive. not enough mineralization. villaneuva strain. too much osteoid, thickened seams. can fix by fixing mineral balance.

Question 31

rickett’s

Answer 31

not enough vitamin D. stress fractures at femoral neck common. bowed legs.

Question 32

sclerosteosis

Answer 32

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.

Question 33

osteopetrosis

Answer 33

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.

Question 34

osteopetrosis histology

Answer 34

paucity of marrow space, full of bone tissue. woven bone, not regular lamellar appearance.

Question 35

Paget’s disease

Answer 35

excessive remodeling in one place. bone is weak, disorganized, poorly mineralized. uncoupled remodeling. woven bone (lacks lamellar structure)

Question 36

Paget’s disease clinical features + labs

Answer 36

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.