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Biochem Exam 5 > Biochemistry of Bone Formation > Flashcards

Biochemistry of Bone Formation Flashcards

1
Q

What are the two types of bone formation?

A

endochondral and intramembranous

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2
Q

What are the four phases of skeletal development?

A
  1. migration of preskeletal cells to sites of future skeletogenesis
  2. interaction of these cells with epithelial cells
  3. interaction leads to mesenchymal condensation
  4. followed by differentiation to chondroblasts or osteoblasts
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3
Q

Characteristics of endochondral bone formation:

A

-indirect
-mesenchyme forms cartilage template first, which is later replaced by bone

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4
Q

Where does endochondral bone formation occur?

A

in most bones of the skeleton
-bones that bear weight and have joints

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5
Q

What type of bone formation occurs during fracture repair?

A

endochondral bone formation

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6
Q

Characteristics of intramembranous bone formation:

A

-direct
-transformation of mesenchyme cells to osteoblasts (no cartilage intermediate)

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7
Q

Where does intramembranous bone formation occur?

A

cranial vault, some facial bones, parts of the mandible and clavicle

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8
Q

What attracts blood vessels to invade during endochondral bone formation?

A

chondrocytes release VEGF

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9
Q

When does growth plate fusion usually occur?

A

around age 14-20 in humans

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10
Q

When do secondary ossification centers appear?

A

around the time of birth

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11
Q

What do osteocytes made by mesenchymal cells do?

A

deposit osteoid (unmineralized) bone matrix

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12
Q

What happens to the osteoid matrix?

A

calcifies/osteoblasts become arranged along calcified region of thematrix

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13
Q

What do the osteoblasts that get trapped in the bone matrix become?

A

osteocytes

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14
Q

What is the first type of bone produced?

A

woven bone (primary bone)

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15
Q

When is woven bone made?

A

when osteoblasts need to form bone rapidly
-embryonic development
-fracture healing
-disease states

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16
Q

What replaces woven bone?

A

lamellar bone

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17
Q

Characteristics of woven bone:

A

-disorganized
-randomly oriented collagen fibrils
-increases cell density
-reduced mineral content

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18
Q

Characteristics of lamellar bone:

A

-highly organized
-concentrically arranged around a central canal containing blood vessels and nerves
-parallel oriented collagen fibers
-mechanically stronger

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19
Q

What are the two types of secondary bone?

A

compact and cancellous bone

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20
Q

What is compact bone?

A

cortical/haversian

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21
Q

What is cancellous bone?

A

spongy/trabecular

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22
Q

What are the three types of bone cells?

A

-osteoclasts
-osteoblasts
-osteocytes

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23
Q

What are osteoblasts derived from?

A

mesenchymal stem cells

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24
Q

What do osteoblasts look like?

A

plump, cuboidal cells located on bone forming surfaces

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25
Q

What do osteoblasts make a lot of?

A

extracellular matrix proteins (collagen type I)

26
Q

What is the lifespan of osteoblasts?

A

weeks

27
Q

What are transcription factors for osteoblasts?

A

Runx2
Osterix

28
Q

What enzymes are associated with osteoblasts?

A

alkaline phosphatase

29
Q

What extracellular matrix proteins are associated with osteoblasts?

A

-type I collagen
-osteopontin
-osteocalcin
-bone sialoprotien (BSP)

30
Q

What does a heterozygous mutation of RUNX2 case?

A

cleidocranial dysplasia

31
Q

Symptoms of cleidocranial dysplasia:

A

-autosomal dominant
-haploinsufficiency of RUNX2
-delayed ossification of midline structures of bone
-clavicles partly or completely missing
-late closing of fontanelle
-supernumerary teeth
-protruding mandible

32
Q

Osterix controls expression of waht osteoblast genes?

A

-type I collagen
-osteocalcin
-osteoporin

33
Q

What does human mutation in osterix associated with?

A

osteogenesis imperfecta type XII

34
Q

What are BMPs associated with?

A

-skeletal development
-differentiation from early osteoprogenitors
-in fracture healing

35
Q

What is fibrodysplasia ossificans progressiva?

A

causes bone to form in the wrong places
-extra skeletal sites
-bones form in response to tissue
-mutations in BMP type I receptor

36
Q

What is being researched as a treatment for fibrodysplasia ossificans progressiva?

A

antibodies against activin A and kinase inhibitors selective for mutation receptors

37
Q

Activating mutations of Lrp5 cause:

A

high bone mass

38
Q

inactivating mutations in Lrp5 cause:

A

low bone mass

39
Q

What initiates the first phase of mineralization?

A

matrix vesicle mediated mechanism

40
Q

What does the second phase of mineralization involve?

A

propagation of mineralization on collagen fibers

41
Q

What is the matrix vesicle?

A

extracellular membrane bound vesicles produced by osteoblasts
30-1000nm in diameter

42
Q

what is inside the matrix vesicle membrane?

A

calcium and phosphate transporters and enzymes that generate phosphate

43
Q

What are the stages of MV mineralization?

A

-amorphous mineral on MV membrane
-HA crystal growth inside MV
-mineral crystals disrupt MV membrane

44
Q

What is alkaline phosphatase?

A

enzyme highly expressed in osteoblasts/odontoblasts

45
Q

What does alkaline phosphatase do?

A

hydrolyze pyrophosphate increasing phosphate concentration
-promote mineralization

46
Q

Mutations in alkaline phosphatase genes are associated with?

A

hypophosphatasia

47
Q

What is hypophosphatasia?

A

rare heritable rickets/osteomalacia
-reduced activity of alkaline phosphatase
-impair mineralization
-varying severity

48
Q

TNSALP mutations associated with:

A

hypophophatasia

48
Q

PHOSPHO1 deletion causes:

A

impaired mineralization

49
Q

ENPP1 mutations associated with:

A

syndrome of spontaneous infantile arterial and periarticular calcification

50
Q

Characteristics of osteocytes:

A

-terminally differentiated osteoblasts
-embedded in bone matrix
-90% of all bone cell s
-long dendritic processes
-lifespan of decades

51
Q

Transcription factors associated with osteocytes:

A

Mef2c

52
Q

Early osteocyte markers:

A

-E11/gp38/podoplanin
-DMP1
-MEPE
-PHEX

53
Q

Last osteocyte marker:

A

SOST

54
Q

Potential functions of osteocytes:

A

-mechanosensors
-control bone resorption and bone formation
-regulate mineralization
-regulate mineral homeostasis
(calcium and phosphorus)

55
Q

What is sclerostin (SOST)

A

negative regulator of bone formation
-antagonize Wnt/beta-catenin signaling

56
Q

Where is SOST expressed?

A

mature osteocytes, cementocytes, and odontoblasts

57
Q

Deletion of SOST in humans causes:

A

Sclereosteosis/ Van Buchems

58
Q

What are side effects of sclerosteosis/Van Buchems?

A

increase bone mass, especially obvious in craniofacial skeleton

59
Q

How do osteocytes play an endocrine role?

A

regulate phosphate homeostasis

Biochem Exam 5 (12 decks)

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