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Perio CT Biochem > bone development > Flashcards

bone development Flashcards

1
Q

What are the core differences between bone and cartilage?

A
  1. calcified and rigid
  2. vascular
  3. contains nerves
  4. dynamic
  5. only appositional growth
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2
Q

What are the functions of the bone?

A
  • structure support for soft tissues
  • protection
  • locomotion
  • metabolic resevoir: stores Ca 99%, PO4 85%, Mg, Na
  • Hematopoiesis: osteoblast support stem cell niche in bone marror and regulate stemness of HSC and immune cells
  • endocrine organ: regulate pancreatic B cell proliferation, insulin synthesis, sensitivity and male fertility through secreted osteocalcin
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3
Q

Why is the bone an ultimate biomaterial?

A

light, strong, adapt to body physiologic and functional demands and repair itself

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4
Q

What is the composition of bone?

A

Mature bone is a composite material and composed of:
30% organic (collagen and noncollagenous proteins)
50% inorganic (minerals)
20% water

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5
Q

What composes of the organic matter of bone?

A

90% of the matrix proteins are collagen;

  • fibers: type 1 collagen, highly organized
  • ground substance: little consists of SLRPs
  • Structural glycoproteins: osteonectin (cell adhesion), osteopontin (cell migration), bone silo protein, osteocalcin (Ca binding)
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6
Q

What is the biological role of fibronectin in bone formation; effect of knockout

A

relatively abundant, regulate osteoblast differentiation

Lethal

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7
Q

What is the biological role of osteonectin in bone formation; effect of knockout

A

bone connector, may regulate mineralization

osteoporosis

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8
Q

What is the biological role of thrombospondin in bone formation; effect of knockout

A

may inhibit bone cell precursors

dense bones

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9
Q

What is the biological role of osteocalcin in bone formation; effect of knockout

A

binds calcium

bones seem normal

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10
Q

What is the biological role of matrix-gla-protein in bone formation; effect of knockout

A

inhibits mineralizations

normal bones but calcified blood vessels

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11
Q

What are the SIBLINGS (small integrin binding ligand, N-linked glycoprotein family) involced with bone formation?

A
  • bone sialoprotein
  • osteopontin
  • matrix extracellular glycoprotein
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12
Q

What is the biological role of bone sialoprotein in bone formation; effect of knockout?

A

binds to integrins, may assist cancer cells

reduced bone formation

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13
Q

What is the biological role of osteopontin in bone formation? Effect of knockout?

A

increases angiogenesis (makes new blood vessels) which enhances bone resorptionin some situations

resistant to ovariectomy and PTH mediated bone loss

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14
Q

What is the biological role of matrix extracellular glycoprotein in bone formation? Effect of knock out?

A

may induce a bone disease called osteomalacia

increased bone mass, osteoblast number, activity

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15
Q

What is the major proteoglycan in bone? Effect of knockout?

A

biglycan

osteopenia

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16
Q

What composes inorganic bone?

A

the mineral component is primarily composed of calcium and phophorous salts and small amounts of magnesium, sodium, and bicarbonate.

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17
Q

What are compositional differences between cartilage and bone?

A

There is mineral in bone but not in cartilage. There is much higher water(70-75%) in cartilage than in bone. Greater fibrillar collagen (20%) in cartilage, only 5% in bone. Greater PGs in cartilage vs bone, less than 1%; major PGs in bone is SLRPs; major PGs in cartilage is aggrecans

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18
Q

What is the function of chondrocytes?

A

responsible for producing cartilage template, growth

and post-natal lengthening of bone.

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19
Q

what is the function of osteoprogenitor cells?

A

fibroblast-like cells in periosteum (outer CT
capsule) and endosteum (inner lining of bone); immature cells but
divide to give appositional growth to bone.

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20
Q

what is the function of osteoblasts?

What are the 3 different fates of osteoblasts?

A

derived from osteoprogenitors; exclusively located at the surface of bone tissue; synthesize and secrete osteoid, which becomes mineralized to give bone; also synthesizes: collagen type 1, proteoglycans, glycoproteins; once differentiated do not divide.

  1. undergo apoptosis
  2. bone lining cells
  3. osteocytes
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21
Q

what is the function of osteocytes?

A

surrounded by matrix, maintain matrix; do not divide; has mechano-sensor abilities

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22
Q

what is the function of fibroblasts?

A

in peri- and endosteum

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23
Q

what is the function of osteoclasts?

A

large multinucleate cells, resemble macrophage in
function, remodel bone by resorbing bone matrix. Derive from monocyte/macrophage lineage, arrive from blood through marrow and blood vessels of haversian canas, periosteum and endosteum

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24
Q

what is the function of endothelial cells?

A

blood vessels

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25
Q

what is the function of neuronal cells?

A

nerves present

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26
Q

Explain the developmental origin of skeletal cells.

A

Different parts of the skeleton are formed by mesenchymal cells derived from three different compartments:

  1. neural crest - gives rise to craniofacial bones
  2. sclerotome/somite - gives rise to most axial skeletal element
  3. lateral plate mesoderm - gives rise to limb bones
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27
Q

What is the first sign of skeletal development?

A

condensation of mesenchymal progenitor cells

28
Q

What signaling pathways are required for skeletal patterning?

A

Wnts, BMPs, FGFs, Hedgehogs, Notch

29
Q

How do osteocytes maintain bone matrix?

A

sclerostin (inhibitor of bone formation)

30
Q

What factors regulate phosphate homeostasis in bone development?

A

FGF-23, Phex, DMP1

31
Q

What is the composition of bone cells in adult skeleton?

A

90-95% osteocytes
4-6% osteoblasts
1-2% osteoclasts

32
Q

What is the bone mineralization process?

A

orchestrated process in which crystals of calcium phosphate are produced by cells and laid down in precise amounts within the fibrous organic matrix

33
Q

what is the primary mineral of bone?

A

hydroxyapetitie

34
Q

What are the 2 way to increase crystal dimension?

A
  1. addition of ions to crystals

2. aggregation of crystal

35
Q

What are factors determining mineralization rate?

A
  • pH
  • concentration of calcium and phosphate
  • ratio of inorganic phosphate and pyrophosphate
  • presence of other ions and charged macromolecules
  • strong anionic proteins have high affinity for Ca2+ therefore they function as hydroxyapetite nucleators
36
Q

What are the types of bone?

A
  1. woven bone (immature/primary)
  2. lamellar bone (mature/secondary)
    - cancellous/trabecular
    - compact/cortical
37
Q

what is the periosteum?

A

covers the outer surface of the bone except articular surface and tendon; it is vascularized and contains osteoprogenitor cells

38
Q

what is the endosteum?

A

consists of marrow stromal cells, resting osteoblasts, and lining cells of the haversian canal

39
Q

What consists of the haversian system?

A

haversian canal, volkmans, canliculi

40
Q

What is the haversian canal?

A

contains blood vessels, nerve cells, and lymphatic vessels

41
Q

what is the volkmann canal?

A

runs perpendicular to the haversian canal; connects blood and nerve supply in the periosteum to those in the haversian canals, endosteum and medullary cavity

42
Q

what is the canaliculi?

A

carry processes for linking osteocytes in adjacent lamallae both within haversian systems and inner and outer circumferntial lamellae; osteocytes contact each other and blood vessels

43
Q

what is the structure of osteon?

A
  • its the haversian system cylinder
  • extends the length of the anatomic bone and composed of 4-20 concentric lamellae arranged in layers
  • haversian canal in the center of osteon
44
Q

Explain the 3D structure of bone

A

Haversian canals at the center of osteons –> volkmanns perpendicular to osteons –>osteocyte processes are linked through canaliculi –>periosteum to endosteum and bone marrow

45
Q

What are examples of intramembranous bone formation?

A

calvaria, maxilla from direct placement of mesenchyme

46
Q

what are examples of endochondral bone formation?

A

long bones, ribs from cartilage template

47
Q

What is intramembranous ossification responsible for?

A

Intramembranous ossification is responsible for frontal, parietal bones and part of occipital, temporal, mandible, and maxilla bones.

48
Q

What is required of intramembranous ossifcation requires?

A
  1. well vascularized primitive CT
  2. bone formation is not preceded by the formation of cartilage
  3. an aggregate of mesenchymal cells differenitates directly into osteoid producing osteoblasts
49
Q

What percentage of postnatal skull growth occurs during the first year of life?

A

85%

50
Q

Due to the pressure of growing brain, how are osteoblasts and osteoclasts contribute?

A

Osteoblasts- add more osteoid on the outside

Osteoclasts- on the inside degrading bone

51
Q

What is craniosynostosis?

A

premature closure of the sutures that disrupts normal brain and skull growth

52
Q

what is deformation plagiocephaly?

A

failed fusion of the skull sutures

53
Q

what is cleft lip and cleft palate?

A

the sides of the lip and roof od the mouth do not fuse together

54
Q

Provide the steps of endochondral bone formation.

A
  1. induction: cartilage template
    - induction of mesenchyme to chondroblasts to form hyaline cartilage; this progresses within limb buds to give a long avascular cartilage template
  2. ossification: conversion of cartilage to bone
    a: Perichondrium converts to periosteum as a collar of bone around the cartilage. This deprives central chondrocytes of
    nutrition by diffusion.
    b: Chondrocytes undergo hypertrophy, resorb cartilage and this
    leads to development of large interconnected spaces.
    c: Space allows blood vessels to enter from periosteum. This
    vascularization allows chondroclasts (like osteoclasts) to arrive
    in blood and accelerate cartilage degradation.
    d: Osteoblasts from progenitor cells in periosteum lay down
    osteoid on spicules of calcified cartilage.
    e: Osteoclasts remodel bone
  3. Bone enlargement: cartilage continues to grow so template lenghtens and widens
  4. Secondary ossifcation:
    cartilage replaced by bone in epipyhsis
  5. growth/remodeling: continues at epiphyseal growth plates until adult (~20 yrs)When growth ceases, diaphysis fuses with epiphyses, spongy bone starts to be destroyed and the space becomes the medullary cavity; only layer of cartilage remains, the articular cartilage, which lacks capacity to repair.
55
Q

Describe the zones of epiphyseal growth plate.

A
  1. Zone of reserve (resting) cartilage: hyaline cartilage
  2. Zone of proliferation: rows of chondrocytes parallel to the direction of bone growth
  3. Zone of maturation/hypertrophy: chondrocytes mature, increase in size
  4. Zone of calcification: chondrocytes die, cartilage matrix becomes calcified
  5. Zone of ossification: osteoprogenitor cells invase and differentiate into osteoblasts, secrete osteoid into calcifed cartilage, mineralization converts this to bone
56
Q

What causes dwarfism?

A
  • excessive FGFR3 signaling (most common)

- GH resistance and deficiency

57
Q

what causes gigantism (child)/acromegaly(adult)?

A
  • excessive GH
58
Q

what does HOX genes do?

A

proximal-distal polarity (should-hand)

59
Q

what does sonic hedgehog do?

A

anterior to posterio limb patterning (thumb to pinky)

60
Q

what does Wnt7, BMP, engrail genes do?

A

dorsal-ventral axis (knuckle-palm)

61
Q

What does Tbx5 do?

A

initiation of forelimb

62
Q

what does mutation in the TBX5 gener cause?

A

Halt oram syndrome

63
Q

What is Runx2 and Sp 7 required for?

A

skelelatogenesis

64
Q

What happens when Runx2 and Sp 7 are deleted?

A

complete lack of mineralized tissue formation and perinatal lethality

65
Q

What occurs with mutation in Runx2 gene?

A

cleidocranial dysplasia - missing clavicles, hypoplastic bone, supernumerary teeth

66
Q

What occurs with mutation in sp7?

A

osteogeneisis imperfecta

Perio CT Biochem (6 decks)

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