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Biochemistry Final Exam > Biology of Fracture Healing > Flashcards

Biology of Fracture Healing Flashcards

1
Q

What are the four phases of skeletal development?

A
  1. Migration
  2. Epithelial-Mesenchymal Interaction
  3. Condensation
  4. Differentiation
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2
Q

What interaction leads to the formation of condensed mesenchymal cells in skeletal development?

A

the interaction of epithelial and mesenchymal cells

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3
Q

The interaction of epithelial cells and mesenchymal cells leads to what phase in skeletal development?

A

mesenchymal condensation

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4
Q

What is the “indirect” way of forming bone?

A

through endochondral bone formation

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5
Q

What is the “direct” way of forming bone?

A

through intramembranous bone formation

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6
Q

Which type of bone formation forms a cartilage template first and then is later replaced by bone?

A

endochondral bone formation

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7
Q

What type of bone formation directly transforms mesenchymal cells into osteblasts?

A

intramembranous bone formation

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8
Q

What type of bone formation occurs in most types of bone, especially those that bear weight or have joints?

A

endochondral bone formation

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9
Q

Which type of bone formation contributes to fracture repair?

A

BOTH

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10
Q

The formation of what structure allows the hypertrophy of chondrocytes to occur?

A

sleeve of bone

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11
Q

What type of chondrocytes release VEGF?

A

hypertrophic chondrocytes

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12
Q

When do secondary ossification centers appear?

A

around the time of birth

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13
Q

What bones undergo intramembranous bone formation?

A

flat bones of the skull; mandible

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14
Q

____ are directly differentiated from mesenchymal cells in intramembranous bone formation, and begin to deposit ____ bone matrix.

A

Osteoblasts; osteoid

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15
Q

What type of bone is the first type of bone produced developmentally?

A

woven bone

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16
Q

What type of bone is woven bone?

A

immature bone

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17
Q

What type of bone is produced when osteoblasts need to produce bone rapidly, like in embryonic development, fracture healing, or disease states such as Paget’s?

A

woven bone

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18
Q

What type of mature bone is produced from remodeled bone?

A

lamellar bone

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19
Q

What are the characteristics of woven bone?

A
  • disorganized
  • collagen fibrils in random orientation
  • increased cell density
  • reduced mineral content
  • lower bifringence
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20
Q

What are the characteristics of lamellar bone?

A
  • highly organized
  • bone lamellae concentrically arranged
  • have Haversian canals
  • collagen in parallel
  • mechanically stronger
  • more bifringence
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21
Q

Secondary or lamellar bone can be further classified into ___ bone and ___ bone.

A

compact (cortical); spongy (cancellous)

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22
Q

An ____ contains Haversian canals, osteocytes, osteocyte lacunae, and canaliculi.

A

osteon

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23
Q

What is skeletal healing essential for in the medical field?

A
  • resolution of orthopedic trauma
  • healing of corrective surgeries of bony deformities
  • bone regeneration in oral surgeries
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24
Q

What cells and their coordinated activity are required in fracture healing?

A 
inflammatory cells
chondroprogenitors
chondrocytes
osteoprogenitors
osteocytes
osteoclasts
vascular cells
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25
Q

What are the phases/stages of fracture healing?

A
  1. Inflammatory Phase
  2. Reparative Phase
  3. Remodeling Phase
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26
Q

When does the inflammatory phase peak and diminish?

A

peaks by 48H; diminished by 1 week

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27
Q

When does the reparative phase activate and eventually diminish?

A

activated within a few days; persists for 2-3 months

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28
Q

In what phase does the formation of a vascular hematoma and inflammation occur?

A

Reactive Phase

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29
Q

In what phase does the formation of a fibrocartilage callous occur, as well as tissue metaplasia with bone mineralization?

A

Reparative Phase

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30
Q

In what phase does bony remodeling and turnover occur?

A

Remodeling Phase

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31
Q

What cytokines does the hematoma release after a traumatic event?

A

TNF-alpha

Interleukins (IL-1, -6, -11, -18)

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32
Q

What does the infiltration of cytokines lead to the recruitment of?

A

inflammatory cells

33
Q

What do the recruited inflammatory cells recruit to the fracture site?

A
  • more inflammatory cytokines
  • mesenchymal stem cells
  • osteogenic precursors
34
Q

The degeneration of what allows the fibrous connective tissue matrix to form?

A

hematoma

35
Q

What is the fibrous connective tissue matrix laid down by? What type of tissue does this form?

A

fibroblasts; granulation tissue

36
Q

What are the broken ends of the bones where blood supply was disrupted afflicted by?

A

hypoxia and tissue necrosis

37
Q

In hypoxic regions of the bone after a fracture, what do the mesenchymal stem cells differentiate into?

A

chondrocytes

38
Q

What type of bone formation occurs in hypoxic regions of a broken bone?

A

endochondral bone formation

39
Q

Where might intramembranous bone form after a fracture?

A

in the periosteal sites (where vascular supply is still intact (callous area))

40
Q

Where do osteogenic precursors (mesenchymal stem cells, pericytes, and muscle satellite cells) come from?

A
  • periosteum/bone marrow
  • circulation
  • muscle
41
Q

What are the basic steps to endochondral ossification?

A
  1. hypertrophy
  2. calcification of cartilage
  3. removal by osteoclasts
  4. replacement with bone
42
Q

When is a fracture considered “healed?”

A

when “clinical union” is observed, when bone tissue completely bridges the original fracture

43
Q

Does the same sequence of bony formation events take place in the healing of alveolar bone in the tooth socket?

A

YES

44
Q

______ includes inflammation, endochondral bone formation, intramembranous bone formation, and osteoclastic bone resorption.

A

Fracture healing

45
Q

What genes are expressed in the inflammation and mesenchymal stem cell recruitment stages of fracture healing?

A 
TNF-alpha
IL-1, 6, 11, 18
TGF-beta
BMP2
GDF-8
46
Q

What genes are expressed in the mesenchymal condensation and early cartilage formation stages of fracture healing?

A

SOX9
type II collagen
PTHrP

47
Q

What genes are expressed in the chondrocyte differentiation and hypertrophy stages of fracture healing?

A

type X collagen
MMP9, 13
alkaline phosphatase
IHH

48
Q

What genes are expressed in the angiogenesis and vascularization stages of fracture healing?

A

HIF1a

VEGF

49
Q

What genes are expressed in the recruitment of osteoclasts to remodel hypertrophic cartilage in fracture healing?

A

RANKL
decreased OPG
M-CSF

50
Q

What genes are expressed in bone formation, both intramembranous and endochondral?

A 
RUNX2
Osterix (OSX)
type I collagen
osteocalcin
VEGF
alkaline phosphastase
51
Q

Formation of a hematoma, recruitment of mesenchymal stem cells, cell proliferation, chondrogenesis/osteogenesis and vascular angiogenesis are all ____ phases of fracture healing.

A

early

52
Q

What are the 3 main categories of signaling molecules important in fracture healing?

A

pro-inflammatory cytokines
TGF-beta superfamily
angiogenic factors

53
Q

____ cytokines recruit other inflammatory cells and promote mesenchymal stem cells in bone formation.

A

Pro-inflammatory; TNF-alpha and IL-1

54
Q

Which types of cytokines induce apoptosis of hypertrophic chondrocytes and promote osteoclast formation?

A

pro-inflammatory cytokines (TNF-a, IL-1)

55
Q

Which cytokines recruit fibrogenic cells and promote formation of granulation tissue?

A

pro-inflammatory cytokines (TNF-a, IL-1)

56
Q

Pro-inflammatory cytokines are secreted by ____, ____, and ____.

A

macrophages; mesenchymal cells; inflammatory cells

57
Q

Which cytokine family promotes extracellular matrix synthesis and assembly/initiation of the callous formation?

A

TBF-beta superfamily

58
Q

What genes promote osteogenic differentiation?

A

TGF-beta
BMP2
GDF-8

59
Q

____ promotes osteogenic differentiation and has a role is cell proliferation.

A

GDF-8

60
Q

What are the TGF-beta superfamily members produced by?

A

hematoma (platelets)
granulation tissue
differentiating MSC
periosteal callous

61
Q

____ promotes vascularization of the periostem, bringing oxygen and osteogenic precursors, like pericytes, to the site.

A

VEGF

62
Q

Where is HIF1a most greatly expressed in?

A

hypoxic regions

63
Q

What is VEGF under the control of?

A

HIF1a

64
Q

What dictates the type of bone healing that will occur?

A

the fracture stability or mechanical environment

65
Q

What type of bone healing will occur if strain is less than 2%?

A

intramembranous bone healing

66
Q

What type of bone healing will occur if strain is 2% to 10%?

A

endochondral bone healing

67
Q

What kind of bone healing will occur if there is high strain, or movement in the fracture area?

A

fibrous tissue formation (non-union)

68
Q

Can bone healing occur as a combination between intramembranous, endochondral, and fibrous bone healing?

A

YES

69
Q

Does zero mechanical loading of the bone promote or delay bone healing?

A

DELAY - so, some mechanical loading is needed to promote healing

70
Q

Are BMPs important in promoting osteogenesis?

A

YES

71
Q

What agents are being shown to be effective in bone healing in clinical use?

A
  • recombinant BMPs
  • platelet rich plasma
  • FGFs
  • PDGF
  • cell-based therapies
  • anti-resorptives
  • bone anabolic agents
72
Q

An ____ bone graft is when a bone is taken from a region of your body and placed into the non-union area.

A

autologous

73
Q

What agent is attempting to replace autologous bone grafts?

A

recombinant BMPs

74
Q

What is FGF signaling important in?

A

skeletal development and fracture healing

75
Q

Where is autologous bone marrow collected from?

A

the iliac crest

76
Q

What does autologous bone marrow collection increase at the site of non-union?

A

increases the number of progenitor cells

77
Q

Sclerostin is an inhibitor of the _____ signaling pathway important for bone formation.

A

Wnt/B-catenin

78
Q

Antibodies to sclerostin would be important in what type of clinical syndrome as a treatment?

A

osteoporosis (inhibiting sclerostin would allow the Wnt/B-catenin pathway to transcribe genes to increase bone density/formation)

Biochemistry Final Exam (8 decks)

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