090814 intro to bone

Question 1

what do osteoblasts differentiate from?

Answer 1

mesenchymal stem cells

Question 2

RUNX2

Answer 2

transcription factor that’s expressed in all cells of the osteoblast lineage

also known as Cbfa-1

Question 3

what do pre osteoblasts make?

Answer 3

low collagen type I and low alkaline phosphatase

Question 4

alkaline phosphatase

Answer 4

breaks pyrophosphate to monophosphate

pyrophosphate inhibits mineralization, so you need alkaline phosphatase for mineralization

Question 5

how can you differentiate mesenchymal stem cells, pre osteoblasts, osteoblasts, and mature osteoblasts/osteocytes?

Answer 5

from the genes they express

Question 6

how do osteoclasts mature?

Answer 6

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

Question 7

cortical bone and trabecular bone differences

Answer 7

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%

Question 8

histology: compact bone vs trabecular

Answer 8

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

Question 9

lamellae are organized how?

Answer 9

in different orientations

Question 10

osteocytes are important for what role?

Answer 10

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

Question 11

intramembranous ossification occurs for what bone?

Answer 11

calvaria

Question 12

chondroblasts’ role in encochondral ossification

Answer 12

they clear away the dead apoptotic chondrocytes and the zone is replaced by osteoblasts

Question 13

growth plates close ate what age?

Answer 13

different ages for different bones

Question 14

bone remodeling in trabecular vs cortical bone

Answer 14

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

Question 15

diff btwn bone remodeling in cortical and cancellous remodeling

Answer 15

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

Question 16

how is bone remodeling like interstate construction?

Answer 16

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

Question 17

which part of bone remodeling is the slowest

Answer 17

mineralization

Question 18

what is used to measure mineralization rate of bone

Answer 18

double tetracycline labeling

Question 19

structure of collagen fibers

Answer 19

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

Question 20

cross link composition is strong when

Answer 20

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)

Question 21

lamellar organization in different directions is important because?

Answer 21

then when you have stress, the strains can get deflected so you get micro or stress fractures instead of more serious injury

Question 22

type I collagen composition

Answer 22

three stranded triple helix composed of two alpha1 chains, one alpha2 chain

Question 23

osteogenesis imperfecta

Answer 23

defect in synthesis of usually collagen by osteoblasts

can result in bowing of bones, disability

Question 24

COLIA1 G748C’s importance

Answer 24

a point mutation results in bent collagen fiber synthesis and thus bone matrix is weak

this is lethal–get breathing problems

Question 25

osteomalacia

Answer 25

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

Question 26

how can you detect osteomalacia

Answer 26

villanueva stain

mineralized matrix is green

osteoid is orange–if you see thickened osteoid, not good

Question 27

rickets

Answer 27

osteomalacia during growth

you see bowing of the legs

can get stress fractures

Question 28

sclerosteosis

Answer 28

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

Question 29

osteopetrosis

Answer 29

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

Question 30

paget’s disease

Answer 30

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

Question 31

labs for paget’s disease show

Answer 31

increased serum alkaline phosphatase (blastic)

urinary hydroxyproline increased (lytic)

Question 32

bone scan

Answer 32

shows where increased or decreased turnover of bone is occurring