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Flashcards in Intro to Bone Deck (27)
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1

What is the signal that allows a mesenchymal stem cell to become a mature osteoblast? 

RUNX2 = Master regulator of bone formation

Mesenchymal Stem Cell --> Pre Osteoblast --> Osteoblast --> Mature Osteoblast

2

What happens if RUNX2 is knocked out? 

No bone formation, lethal

Heterozygous form -- severe craniofacial deformations

3

What is in bone canaliculi? 

Processes from osteocytes that connect cells -- communicate via gap junctions encoded by connexin 43

No connexin 43 = problems with bone formation

4

What is the dual signalling that is required for the differentiation cascade of osteoclasts?

m-CSF & RANK-L -- activate specific osteoclast pathway to initiate the development of osteoclasts

5

What does TRAP do? 

TRAP = tartate resistant and acid phosphatase 

Fuses to become macrophages -- makes sealing zone around bone they will resorb

6

What is the sealing zone's function? 

Ruffled border on osteoclast to increase the amount of surface area to secrete H+ and Kathepsin K, adheres to bone matrix and dissolves mineral in bone 

7

Cortical bone 

  • 80-90% of volume is calcified 
  • Fulfills mainly a mechanical and protective function
  • Always found on outside of bones and surrounds trabecular bone 
  • 4/5 of skeleton 

8

Trabecular Bone 

  • 15-20% of volume is calcifed 
  • Fulfills mainly a metabolic function
  • 1/5 of bone volume 

9

How does the histology of cortical and trabecular bone differ? 

Cortical bone has layers that are organized around a channel, difference in orientation of type I collagen fibers in matrix 

Trabecular bone is organized in plates/rods and interspersed wtih adipose/hematopoietic tissue 

10

Why are osteocytes considered the orchestrators of bone turnover and what protein helps mediate this? 

Osteocytes can sense force on skeleton to determine where bone will be deposited and absorbed.

Sclerostin: expressed by osteocytes, inhibits maturation of osteoblasts -- when a bone is mechanically loaded, stop making Sclerostin so osteoblasts can make bone!

11

Intramembranous ossification

Form directly from dense connective tissue

12

What kind of ossification occurs at the growth plate? 

Endochondral ossification: linear growth in length of long bone mediated by division of chondrocyte.

Cartilage in growth plate is doing the growing and bone comesin to replace the cartilage, then bone plate fuses and linear growth stops!

13

What digests away calcified cartilage in endochondral ossification? 

Chondroclasts 

14

What is the remodeling cycle like for Trabecular or cancellous bone? 

  • 12 bone remodeling units activated each minute, with annual turnover rate of 25%
  • High turnover rate because of higher surface-to-volume ratio
  • Complete remodeling cycle takes 4-6 months 
  • Osteoid laid down in discrete layers, 3 micrometer thick 
  • Lamellae deposited in curved sheets that follow the contour of the trabeculae 

15

Remodeling cycle for cortical or compact bone 

  • 3 bone remodeling units activated each minute with annual turnover rate of 2-3%
  • Lower turnover rate
  • Less vascularity 
  • Remodeling cycle takes 4-6 months 
  • Osteoblasts plus blood vessels follow osteoclasts through hollowed-out tunnel 
  • Concentric lamellae laid down 

16

What can be used to meausre mineralization rate? 

Tetracycline labeling: Tet binds tightly to front of mineralization in newly formed osteoid -- put bone under fluroescent light and see bright yellow bands where tet was deposited. In path lab can measure the distance between them and will give you microns per day of growth 

17

What are the stages in fracture healing? 

1. Hematoma formation

2. Fibrocartilaginous callus formation 

3. Bony callus formation

4. Bone remodeling 

18

Assembly of pro-alpha collagen and processing into Tropocollagen 

Type I collagen is the most abundant protein in bone. 

3 strands wound together in left handed triple helix, globular domains at ends cleaved off and assembled mature protein is secreted into extracellular space.

Gives tensile strength to resist being pulled apart 

19

How are collagen cross-links formed? 

Form from lysines in neighboring chains in enzymatic fashion. Mature to aromatic form called pyridinoline which are non-reducable and really strong. Mature collagen has high tensile strength with adequate density of x-links. 

20

Is it easier to form breaks against lamellae grain or with lamellae grain? 

With lamellae grain -- the amount of energy to produce the two is different 

21

Disease that arises from osteoblast's defective synthesis of the organic component of bone matrix. 

Osteogenesis Imperfecta 

22

What is a common cause of Osteogenesis Imperfecta? 

Mutations in type 1 collagen alpha1 or 2 chain -- leads to bent and frayed collagen molecules that do not assemble properly --> weak bone 

23

Defective bone mineralization secondary to inadequate amounts of available phosphorus and calcium (vit D). 

Osteomalacia 

24

Defect in osteocytes where there is a mutation in sclerostin. If sclerostin doesnt work, bone thinks it is always loaded and leads to overgrown bones and nerve entrapment, facial palsy and deafness. 

Sclerosteosis 

25

Osteoclasts are unable to resorb bone during remodeling -- abnormally high bone density. 

Osteopetrosis 

26

Uncoupled remodeling gone wild.

Pain, osseous bowing and enlargement, neurologic symptoms. 

Lab: increased markers of bone turnover -- serum alkaline phosphatase, urinary hydroxyproline. 

Presdisposition to osteosarcoma. 

Paget's Disease

27

What is the treatment for Paget's disease? 

Bisphosphonates to stop osteoclasts in their tracks and let everything heal