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Biochem Exam 5 > Fracture Healing > Flashcards

Fracture Healing Flashcards

1
Q

a multipotent stem cell that has the capacity to differentiate into a variety of cell types, including fibroblasts, osteoblasts, muscle cells, adipocytes, chondrocytes.

A

Mesenchymal Stem Cell (MSC)

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2
Q

condensation of mesenchymal stem cells into a more dense mass of cells to initiate the formation of a bone rudiment

A

Mesenchymal Condensation

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3
Q

a process for formation of bone in which a cartilage template is made first, which is then replaced by bone.

A

Endochondral Bone Formation

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4
Q

cartilage in which the chondrocytes have undergone hypertrophy. This includes swelling of the cell volume, mineralization of the surrounding matrix, expression of marker genes of hypertrophy (see class on chondrocytes). In the final stages, the hypertrophic chondrocytes will undergo apoptosis.

A

Hypertrophic Cartilage

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5
Q

a process for formation of bone in which there is direct transformation of the mesenchymal precursor cells into bone forming osteoblasts without a cartilage intermediate.

A

Intramembranous Bone Formation

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6
Q

the type of bone that is laid down initially during endochondral or intramembranous bone formation and in situations such as fracture healing where there is a need for rapid deposition of bone. The collagen fibers are more randomly oriented and the tissue is much less organized than lamellar bone.

A

Woven Bone (Primary Bone)

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7
Q

bone that is formed after the woven (primary) bone is resorbed by osteoclasts (bone remodeling). The structure consists of concentric lamellae of bone surrounding a “Haversian canal” which contains a blood vessel and nerves. Collagen is more organized (often fibers run parallel to the long axis of the bone) and osteocytes are organized in concentric rings around the Haversian canal.

A

Lamellar Bone (Secondary Bone/Haversian Bone)

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8
Q

a complication of bone fracture in which the bone does not heal.

A

Non-union

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9
Q

the process by which bone is removed by osteoclasts and replaced with new bone

A

Bone remodeling

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10
Q

a disorganized network of cartilage/woven bone formed between the ends of the broken bone and extending beyond the original contour of the bone. The callus is ultimately replaced by lamellar bone following remodeling

A

Fracture Callus

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11
Q

a fancy word for a blood clot

A

Hematoma

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12
Q

a tissue containing newly formed vascular tissue and fibrous extracellular matrix, usually formed in healing wounds

A

Granulation Tissue

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13
Q

a cell that is present in the wall of capillaries and has mesenchymal stem cell properties since it can differentiate into other cell types such as muscle, fibroblasts, osteoblasts, etc.

A

Pericyte

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14
Q

these are small cells found in mature muscle that have stem cell-like properties and provide a source of progenitors for formation of muscle cells, especially in situations of muscle injury/repair. They may also be able to differentiate into osteoblasts.

A

Muscle Satellite Cell

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15
Q

the ability to form cartilage

A

Chondrogenic

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16
Q

the ability to form bone

A

Osteogenic

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17
Q

a condition in which a region of the body is deprived of an adequate oxygen supply.

A

Hypoxia

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18
Q

the formation of new blood vessels (from outgrowth of pre-existing vessels). This is different from vasculogenesis in which new blood vessels form de novo.

A

Angiogenesis

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19
Q

the directional movement of cells towards certain chemicals

A

Chemotaxis

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20
Q

a superfamily of structurally and evolutionarily related proteins that includes the transforming growth factor betas (TGFβs), the bone morphogenetic proteins (BMPs), activins, inhibins and growth and differentiation factors (GDFs)

A

Transforming Growth Factor Beta Superfamily

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21
Q
  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
A

Four Phases of Skeletal Development

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22
Q
  • Indirect - mesenchyme forms cartilage template first, which is later replaced by bone
  • Occurs in most bones in the skeleton – esp. bones that bear weight and have joints • Also occurs during fracture repair
A

Endochondral Bone formation

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23
Q

• Direct transformation of mesenchymal cells to
osteoblasts (no cartilage intermediate)
• Restricted to cranial vault, some facial bones, parts of the mandible and clavicle
• Contributes to fracture repair

A

Intramembranous Bone Formation

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24
Q

Growth plate fusion occurs around age __-__ in humans depending on the specific bone and the gender of the individual

A

14-20

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25
Q

________ ossification center appears around the time of birth

A

Secondary

26
Q

Which Bone formation process excludes a cartilage model proceding the bone formation.

A

Intramembraneous

27
Q

First type of bone produced developmentally

A

woven Bone

28
Q

Which type of bone is produced rapidly in development and in fracture healing?

A

Woven Bone

29
Q

What are the two types of Lamellar Bones??

A
  • Compact:
    (Cortical/ Haversian)
  • cancellous:
    (Spongy/ trabecular).
30
Q

The inflammatory (reactive) phase peaks by __ hours and is deminished by __ week (s).

A

48; 1

31
Q

he reparative phase lasts up to _ - _ months

A

2-3 months

32
Q

What are the four phases of fracture repair:

A
  • -Reactive–
    1) Formation of vascular hematoma.
  • -Reparative–
    2) Formation of (fibrocartilage) callus
    3) Tissue metaplasia – callus replaced by mineralized bone
  • -Remodeling–
    4) Bone remodeling and turnover
33
Q

What cytokines are released in association to the hematoma?

A

Tumor necrosis factor-α (TNF-α )

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

34
Q

______ lead to recruitment/infiltration of inflammatory cells.; These inflammatory cells will release more of these which will lead to the recruitment of mesenchymal stem cells. (MSC)

A

cytokines

35
Q

What are key events of the formation of the fibrocartilagenous callous?

A
  1. MSC/ connective tissues stem cells/ and blodd vessels invade the hematoma.
  2. hematoma degenerates.
  3. granulation tissues is laid by fibroblasts.
  4. where the bone was broken become hypoxic and here the MSC differentiate into chondrocytes (endochondral bone formation).
36
Q
  • Periosteum
  • Muscle
  • Bone Marrow
  • Circulating
A

four sources for osteogenic precursors

37
Q
  • Mesenchymal Stem Cell (MSC)
  • Pericyte
  • Muscle satellite cell
A

Types of osteogenic precursors.

38
Q

Fracture considered healed when bone

stability restored by bone tissue completely bridging the original fracture

A

clinical union

39
Q

• Initial woven bone must be remodeled
• Osteoclasts resorb woven bone in
fracture callous then osteoblasts lay down new lamellar bone (Haversian) = mechanically stronger
• Restores marrow cavity
• Restores original contours of bone
• Biomechanical stability matches that of
the original bone

A

Remodeling

40
Q

Types of genes expressed for Inflammation/ MSC recruitment

A

TGFβ superfamily members

Pro-inflammatory cytokines

41
Q

Types of genes expressed for Mesenchymal Condensation/early cartilage formation

A

Early chondrogenic markers

42
Q

Types of genes expressed for Chondrocyte differentiation/hypertrophy

A

Late (prehypertrophic and hypertrophic) chondrocyte markers

43
Q

Types of genes expressed for Angiogenesis/vascularization

A

Angiogenic factors

44
Q

Types of genes expressed for Recruitment of osteoclasts to remodel hypertrophic cartilage

A

Osteoclastogenic factors

45
Q

Types of genes expressed for Osteogenic markers and angiogenic factors

A

Osteogenic markers and angiogenic factors

46
Q

What are the three main categories of Signaling Molecules Important in Fracture Healing

A

pro-inflammatory cytokines

TGFB superfamily members

angiogenic factors

47
Q

What are the two types of Pro-Inflammatory Cytokines

A

Tumor necrosis factor-α (TNF-α)

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

48
Q

What are the functions of Tumor necrosis factor-α (TNF-α) and Interleukins (IL-1,-6, -11 and -18)

A

recruit other inflammatory cells/ promote MSC recruitment

induce apoptosis of hypertrophic chondrocytes

recruit fibrogenic cells/ promote formation of granulation tissue/ ECM formation

can promote osteoclast formation

49
Q

What secrete pro-inflammatory cytokines?

A

macrophages

mesenchymal cells and inflammatory cells.

50
Q

Transforming growth factor-β (TGFβ) Bone morphogenetic protein-2 BMP2 (also 5,6) Growth and differentiation factor-8 (GDF-8)

A

TGFβ Superfamily Members

51
Q

Functions of ______ include:
− Promote osteogenic differentiation
− GDF-8 – role in cell proliferation
− Promote ECM synthesis & assembly/initiation of callus formation

A

What are the major functions of TGFβ Superfamily Members?

52
Q

What cells produce TGFβ Superfamily Members?

A

Produced by hematoma (platelets)/ granulation tissue/differentiating
MSC/periosteal callus

53
Q

VEGF - Vascular endothelial growth factor PDGF - Platelet derived growth factor ANGPT - Angiopoietin

A

Angiogenic Factors

54
Q

− promotes chemotaxis of osteoprogenitors

-upregulated in regions of hypoxia

A

VEGF

55
Q

₋ If strain <2%_________ bone healing will occur

A

intramembranous

56
Q

₋ If strain is >2% <10%_________ bone healing will occur

A

endochondral

57
Q

• Appear to be effective alternative to autologous bone graft for repair of fracture non union/open tibial fractures.

A

BMPs

Bone Morphogenic Protein

58
Q

______ _____ ____ _ is shown to enhance fracture healing. However, if exposed for too long it can impair mineralization, so timing is key.

A

Fibroblast Growth Factor 2

59
Q

Autologous bone marrow collected from iliac
crest/injected into non-union site (increases #
of progenitor cells)

A

Cell-Based Therapies

60
Q

Inhibitor of Wnt/β-catenin signaling (important pathway for bone formation)

A

Sclerostin

61
Q

T/ F: Anti-Sclerostin Antibodies Promote Bone Healing

A

True

Biochem Exam 5 (9 decks)

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