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MM Test 3 > B6.068 Prework 1: Bone Development Overview / Appendicular Skeleton > Flashcards

B6.068 Prework 1: Bone Development Overview / Appendicular Skeleton Flashcards

1
Q

why is bone a tissue?

A

mineralized connective tissue
comprised of different cell types that communicate with one another
continuously remodeled
processes under local and systemic hormonal control

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2
Q

how is bone modeling orchestrated

A

by osteocytes in response to mechanosensors

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3
Q

local control of bone modeling

A

growth factors

cytokines

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4
Q

systemic hormonal control of bone modeling

A

calcitonin

estrogen

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5
Q

why is bone an organ

A

collectively comprises the skeletal system

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6
Q

functions of the skeletal system

A

locomotion
structural support
protection for internal organs
mineral reservoir for calcium and phosphate (Ca homeostasis)
contains bone marrow which produces red and white blood cells
endocrine regulation

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7
Q

endocrine function of bone

A

produces osteocalcin

hormone that has a role in bone mineralization, calcium ion homeostasis, and insulin metabolism

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8
Q

embryologic components of the skeletal system

A

a) paraxial mesoderm
b) lateral plate mesoderm (parietal)
c) cranial neural crest cells
d) mesenchyme of dermis

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9
Q

how does the paraxial mesoderm contribute to the skeletal system

A

forms somitomeres cranially and somites from the occipital to sacral region

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10
Q

ventral portion of the somite

A

sclerotome

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11
Q

sclerotome contribution to skeleton

A

becomes mesenchymal at the end of the 4th week
comprised of loosely organized connective tissues
mesenchymal cells can migrate and differentiate to form multiple cell types (fibroblasts, chondroblasts, osteoblasts)
caudal portion gives rise to vertebral column and ribs

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12
Q

cranial vault and base of skull origin

A

paraxial mesoderm:
somitomeres
occipital somites

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13
Q

parietal lateral plate mesoderm contribution to skeletal system

A

bones of pelvic and shoulder girdles
long bones of limbs
sternum

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14
Q

neural crest cell contribution to skeletal system

A

bones of face and skull

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15
Q

mesenchyme of dermis contribution to skeletal system

A

flat bones of the skull

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16
Q

osteoblast origin

A

mesenchymal stem cells in periosteum

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17
Q

osteoblast function

A

secrete the matrix (collagen 1 rich osteoid)
catalyze mineralization (calcification) of osteoid via secretion of alk phos to make bone
become trapped in the matrix they secrete

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18
Q

osteocytes

A 
mature bone cells w dendritic processes
formed when osteoblasts become trapped
maintain bone
role in mineral homeostasis via FGF23
sense mechanical load
viable for decades
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19
Q

osteoclasts

A

dissolve/absorb bone during growth by secreting H+ and collagenases

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20
Q

osteoclast origin

A

differentiate from a fusion of monocyte/ macrophage lineage precursors to form large multinucleate bone cells

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21
Q

RANK signaling pathway

A

regulates osteoclast differentiation and activation, and bone remodeling/repair

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22
Q

RANK

A

receptor activator for NFKB

  • TNF receptor family
  • present on pre-osteoclasts and osteoclasts
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23
Q

RANK-L

A

expressed by osteoblasts
activates RANK & transcription factor NFKB
role in osteoclast formation, differentiation and survival

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24
Q

chondroblasts

A

mesenchymal progenitor cells which will form chondrocytes in the growing cartilage matrix

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25
Q

chondrocytes

A

produce and maintain the cartilaginous matrix

articular + hyaline model for bone formation

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26
Q

chondroclasts

A

involved in resorption of calcified cartilage

multinucleated (giant) cells

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27
Q

discuss the steps of neural crest cells forming craniofacial cartilage and bone

A
  1. arise from border of non neural and neural ectoderm
  2. neural ectoderm rolls up to form neural tube
  3. epithelial cells in dorsal portion of the neural tube undergo epithelial to mesenchymal transformation
  4. neural crest migrate out and away from neural tube
  5. forms head and neck
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28
Q

compact bone

A

cortical

hard, dense, found near surface where strength is required

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29
Q

spongy bone

A

cancellous, trabecular

mesh like, found in ends of long bones and center of flat bones

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30
Q

bone marrow

A

loose CT that fills cavities of bone

produces red and white blood cells

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31
Q

periosteum

A

CT on the surface of bone
outer fibrous layer = nerves and BVs
inner layer = osteogenic cells

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32
Q

endosteum

A

inner lining of bones

lines bone marrow cavity

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33
Q

Haversian canal

A

duct in bone w blood vessels

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34
Q

Osteon / Haversian system

A

functional unit of compact bone

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35
Q

canalicular system of bones

A

tiny canals extending from one lacuna to another

connect osteocytes

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36
Q

vascularity of bones

A

bone cells must be in close proximity to capillaries

vessels present in bone marrow, Haversian canals, and periosteum

37
Q

elongation of bones

A

involves epiphysial cartilages at the ends of the long bone, but it is the diaphysis that increases in length

38
Q

newly formed bone vs matured bone

A

new: appears woven w haphazard strands of collagen

eventually transforms to be lamellar (parallel arrays of mineralized osteoid)

39
Q

4 phases of skeletal development

A
  1. migration of pre-skeletal mesenchymal cells to sites of future skeletogenesis
  2. interaction of mesenchymal cells with epithelial cells
  3. interaction leads to mesenchymal condensation
  4. followed by differentiation to chondroblasts or osteoblasts
40
Q

2 types of bone formation

A

intramembranous ossification

endochondral ossification

41
Q

intramembranous ossification

A

mesenchyme differentiated directly into osteoblasts, which form bone
e.g. flat bones of skull

42
Q

endochondral ossification

A

mesenchymal cells give rise to chondroblasts, which differentiate to chondrocytes which make mineralized cartilage models
cartilage models replaced by bone
e.g. base of skull, limb long bones, end of irregular bones (ribs and vertebrae)

43
Q

steps of intramembranous ossification

A
  1. mesenchymal cells group into clusters and form multiple cell types; osteoblasts form ossification centers
  2. secreted osteoid becomes calcified and traps osteoblasts which become osteocytes
  3. trabecular matrix forms from osteoid and periosteum forms from surface osteoblasts
  4. compact bone develops superficial to the trabecular bone, and crowded blood vessels condense into red marrow
44
Q

time line of intramembranous ossification

A

begins in utero

continues into adolescence

45
Q

last bones to ossify

A

flat bones of face (at end of adolescence)

46
Q

benefits of later intramembranous ossification

A

skull sutures and clavicles are not fully ossified at birth, skull and shoulders deform during passage through the birth canal
skull can increase in size to allow for postnatal bone growth

47
Q

primary ossification centers

A

part of endochondral ossification
present in long bones by week 12 of development
responsible for prenatal bone growth

48
Q

secondary ossification centers

A

ends of bone

where growth progresses after birth

49
Q

epiphysis

A

articular portion of long bones

50
Q

metaphysis

A 
site of secondary ossification
3 subportions:
-epiphysial plate (cartilaginous)
-bony portion
-fibrous component (periphery of growth plate)
51
Q

diaphysis

A

midportion (shaft)
portion of bone that contains the medullary cavity
lengthens due to action of growth plates in metaphyses
contains primary ossification center

52
Q

how does the primary ossification center form

A
  1. mesenchymal cells differentiate into chondroblasts, then chondrocytes
  2. cartilage model of the future bony skeleton and perichondrium form
  3. capillaries penetrate cartilage, bringing osteoblasts / perichondrium transforms to periosteum / periosteal collar develops around mineralized cartilage / primary ossification center develops (in diaphysis)
  4. cartilage and chondrocytes continue to grow at ends of the bone
53
Q

development of secondary ossification centers

A

at birth: the diaphysis is ossified and 2 ends of bone are still cartilaginous
vessels invade epiphyses
secondary ossification continues in epiphyses

54
Q

when do epiphysial plates disappear

A

approx. age 13-15 in females, 15-17 in males

55
Q

bone age information

A

derived from ossification centers in hands and wrists

56
Q

how is a cartilage model formed

A

chondrocytes secrete collagen type 2 and sulfated proteoglycans

57
Q

what happens after a cartilage model is formed

A

chondrocytes move away from ends of bone, begin to hypertrophy & secrete alk phos
collagen is reorganized into hexagonal lattices due to production of collagen type X
ECM becomes calcified by calcium phosphate
chondrocytes eventually undergo apoptosis

58
Q

why do chondrocytes undergo apoptosis?

A

matrix mineralizes and nutrients can no longer reach them because cartilage is avascular

59
Q

what happens when chondrocytes die?

A

secrete matrix metalloproteinases to degrade ECM

blood vessels invade resulting spaces, enlarging the cavities and bringing osteoblasts and chondroblasts

60
Q

what are the 5 zones of the epiphyseal plate

A 
EPIPHYSIS
reserve/ resting zones
proliferation zone
hypertrophic cartilage zone
zone of calcification of cartilage
zone of ossification
61
Q

reserve/resting zone

A

chondrocytes anchor plate to osseous tissue of epiphysis

62
Q

proliferation zone

A

chondrocytes proliferation

63
Q

hypertrophic cartilage zone

A

chondrocytes increase in size, accumulate alk phos

64
Q

zone of calcification of cartilage

A

chondrocytes apoptose; cartilaginous matrix begins to calcify

65
Q

zone of ossification

A

osteoclasts and osteoblasts from the diaphyseal side break down the calcified cartilage and replace with mineralized bone (type 1 collagen)

66
Q

what types of bones undergo appositional growth

A

occurs in all bones!
when bones increase in length, they also increase in diameter
diameter growth continues after longitudinal growth ceases

67
Q

cells involved in appositional growth

A

osteoclasts resorb old bone that lines the medullary cavity
osteoblasts produce new bone tissue beneath periosteum
subperiosteal cortical bone forms and an increase in bone diameter results

68
Q

how many bones in the shoulder girdle

A

4

clavicle and scapula each side

69
Q

how many bones in the arm and forearm

A

6

humerus, ulna, radius

70
Q

how many bones in the hand

A 
58
16 carpals
10 metacarpals
28 phalanges
4 sesamoid
71
Q

how many leg bones

A

8

femur, tibia, patella, fibula

72
Q

epidemiology of achondroplasia

A

most common form of skeletal dysplasia

1/20,000 live births

73
Q

genetics of achondroplasia

A

autosomal dominant

related to FGF Receptor 3 mutations

74
Q

systems impacted by achondroplasia

A

endochondral ossification in long bones and formation of base of skull

75
Q

effects of achondroplasia

A

short limbs and fingers
large skull
small midface
prominent forehead

76
Q

effects of Marfan Syndrome

A 
long limbs
long face
sternal defects
dilation and dissection of ascending aorta
lens dislocation
77
Q

genetics of Marfan

A

fibrillin 1 gene mutations

78
Q

when do symptoms of Marfan appear?

A

symptoms may not appear / be diagnosed until late in childhood / early adulthood

79
Q

what is congenital hyperpituitarism

A

production of excess growth hormone

80
Q

acromegaly

A

growth of soft tissues (enlargement of face), ad bones of hands and feet

81
Q

gigantism

A

excessive growth (height and body proportions)

82
Q

what is hypopituitarism

A

growth hormone is affected

83
Q

effects of hypopituitarism

A

short stature
fat around waist and face
delayed teeth development
sluggish hair growth

84
Q

congenital rickets

A

caused by severe maternal def in vit D
rare
results in defective mineralization of cartilaginous plates

85
Q

what is osteogenesis imperfecta

A

reduced type 1 collagen production and altered bone matrix
hypomineralization of the long bones of limbs
improper bones form

86
Q

bone effects of osteogenesis imperfecta

A

shortened, bowed, easily fractured bones
frequent and multiple fractures
bowing of bones and curvature of spine can result in short stature

87
Q

genetics of osteogenesis imperfecta

A

90% linked to defects in COL1A1 or COL1A2

88
Q

non-bone effects of osteogenesis imperfecta

A

skin, muscles, joints, teeth, hearing, blue sclera

MM Test 3 (31 decks)

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