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MM3 Leesy > B6.068 - Bone Development Prework > Flashcards

B6.068 - Bone Development Prework Flashcards

1
Q

what is bone

A

tissue and organ

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2
Q

describe bone as a tissue

A

mineralized connective tissue
comprised of osteoblasts, osteocytes, osteoclasts
continuously remodeled

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3
Q

what orchestarates continuous remodeling of bone

A

balancing resorption by osteocytes and osteoclasts & formation of osteoblasts

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4
Q

what orchestrates bone modeling

A

osteocytes in response to mechanosensors

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5
Q

what helps with local control of bone

A

growth factors, cytokines

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6
Q

what helps with systemic hormonal control of bone

A

calcitonin, estrogen

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7
Q

describe endocrine regulation by bone

A

produces osteocalcin (hormone that has a role in bone mineralization, calcium ion homeostasis, insulin metabolism)

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8
Q

what does the skeletal system develop from

A
  1. paraxial mesoderm
  2. lateral plate mesoderm
  3. cranial neural crest cells
  4. mesenchyme of dermis
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9
Q

paraxial mesoderm forms what

A

somitomeres cranially, somites from occipital to sacral region

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10
Q

what happens in the 4th week of development to the somite

A

the ventral portion (sclerotome) becomes mesenchymal and some cells migrate and differentiate into fibroblasts, chondroblasts or osteoblasts

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11
Q

what contributes to the formation of the cranial vault

A

somitomeres and occipital somites

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12
Q

what happens to the caudal sclerotome

A

it gives rise to the vertebral column and ribs

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13
Q

what forms the bones of the pelvic and shoulder girdles, long bones of limbs and sternum

A

bone forming cells in the parietal/somatic layer of LPM

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14
Q

what contributes to the bones fo face and skull

A

neural crest cells

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15
Q

what happens in the flat bones of the skull

A

mesenchyme in the dermis differentiates directly into bone

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16
Q

where do osteoblasts come from

A

differentiate from mesenchymal stem cells in periosteum or are delivered by blood vessels

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17
Q

what do osteoblasts do

A 
secrete matrix (collagen 1 rich osteoid); catalyze mineralization (calcification ) of bosteoid via secretion o falk phosphatase to make bone
they then become trapped in the matrix they secrete
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18
Q

what are osteocytes

A

mature bone cells, have dendritic processes; formed when osteoblasts become trapped; maintain bone; role in mineral homeostasis via secretion of FGF23; sense mechanical load; viable for decades

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19
Q

what are osteoclasts

A

dissolve/absorb bone during growth by secreting H+ and collegenases. Differentiate from a fusion of monocyte/macrophage lineage precursors to form large multinucleated bone cells

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20
Q

what is RANK

A

a receptor for RANKL a pathway that regulates osteoclasts differentiation and activation. bone remodeling/repair
RANK - receptor activator for nuclear factor kapp abeta

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21
Q

describe RANK signaling

A

TNF receptor family member

present on osteoclasts and blasts

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22
Q

describe RANKL

A

expressed by osteoblasts

activates RANK and TF NFkB role of osteoclasts formation, differentiation and survival

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23
Q

what are chondroblasts

A

mesenchymal progenitor cells which will form chondrocytes in growing cartilage matrix

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24
Q

what are chondrocytes

A

produce and maintain the cartilagenous matrix (articular cartilage or cartilage model for bone formation)

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25
Q

chondroclasts

A

involved in resorption of calcified cartilage; multinucleated giant cells

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26
Q

mesenchymal cells

A

multipotent; can differentiate in to osteoblasts, chondrocytes, other

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27
Q

what are neural crest cells

A

contribute to craniofacial cartilage and bone formation
arise from border of non neural and neural ectoderm
neural ectoderm rolls up to form neural tube

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28
Q

what happens in dorsal portion of neural tube

A

epithelial cells in dorsal poriton of neural tube undergo epithelial to mesenchymal transformation

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29
Q

compact bone

A

cortical, hard, dense, found near surface where strength is required

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30
Q

spongy bone

A

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

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31
Q

bone marrow

A

loose connective tissue that fills cavities of bone; produces red and white blood cells

32
Q

periosteum

A

CT on surface of bone

outer fibrous layer has nerves and blood vessels; inner layer contains osteogenic cells

33
Q

endosteum

A

inner lining of bones. Lines bone marrow cavity

34
Q

haversian canal

A

duct in bone that contains blood vessels

35
Q

osteon/haversian system

A

functional unit of compact bone

36
Q

canalicular system

A

tiny canals extending from one lacuna to another connect ostocytes

37
Q

elongation of bone

A

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

38
Q

where are sensory neurons in bone found

A

haversian canal and periosteum

39
Q

what are the 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

what are the 2 types of initial bone formation

A
  1. intamembranous ossification

2. endochondral ossification

41
Q

what is intramembranous ossification

A

mesenchyme differentiates directly into osteoblasts, which form bone (flat bones of skull)

42
Q

what is endochondral ossification

A

mesenchymal cells give rise to chondroblasts, which differentiate into chondrocytes which make mineralized cartilage models (as an intermediate)

43
Q

what are cartilage models

A

replaced by bone later in development

44
Q

describe the process of intramembranous ossification

A
  1. mesenchymal cells group into clusters and form multiple cell types; osteoblatss form ossification centers
  2. secreted osteoid (unmineralized bone matrix) becomes calcified and traps oteoblasts which become osteocytes
  3. trabecular matrix forms from osteoid and periosteum forms from surface osteoblasts
  4. compact bone develops superficial to trabecular bone, and crowded blood vessels condense into red marrow
45
Q

timeline of intramembranous ossification

A

begins in utero and continues in to adolescence

the last bones to ossify are the flat bones of the face, at the end of adolescence

46
Q

benefits of intramembranous ossification

A

since the skull sutures and clavicles are not fully ossified at birth, the skull and shoulders deform during passage through the birth canal. The skull can also increase in size after birth for brain growth

47
Q

bone formation from cartilage models

A

bones in extremities formed initially by endochondral ossification
involves primary and secondary ossification centers

48
Q

primary ossification centers

A

in long bones by week 12; responsible for prenatal bone growth in length

49
Q

secondary ossification centers

A

in ends of bone

50
Q

how does ossification of bone progress

A

from center of shaft (primary oss) to ends of bone (secondary oss)

51
Q

what are the 3 dynamic regions of a long bone

A

epiphysis
metaphysis
diaphysiss

52
Q

what is the metaphysis

A

site of secondary ossification centers; 3 subportions:

  1. epiphyseal plate
  2. bony portion
  3. fibrous component
53
Q

diaphyiss

A

mid portion/portion of bone that contains the medullary cavity; lengthens due to action of growth plates in metaphyses; is portion of bone that contains primary ossification center

54
Q

describe the primary ossification center

A

endochondral ossification
mesenchymal cells differentiate into chondroblasts, then chondrocytes
cartilage model of future bony skeleton and perichondrium form. Capillaries penetrate cartilage; bringing osteoblasts. Perichondrium transforms into periostum and periosteal collar develops around mineralized cartilage. Primary ossification center develops

55
Q

describe growth plates at birth

A

diaphysis is ossified
2 ends are still cartilaginous
vessels invade epiphyses
secondary ossification continues in epiphyses
when bone at full length epiphyseal plates dissapear (age 13-15 F, 15-17 M)

56
Q

where is bone age derived from

A

ossification centers in hands and wrists

57
Q

cartilage matrix formation

A

following proliferation, chondrocytes secrete mostly collagen type 2 and sulfated proteoglycans forming cartilage model. Then chondrocytes move away from ends of bone and start to hypertrophy and secrete alkaline phosphatase. collagen reorganized into hexagonal lattices due to production of collagen type X
ECM becomes mineralized/calcified by calcium phosphate
chondrocytes eventually undergo apoptosis

58
Q

describe vascularization of bone

A

chondrocytes undergo apoptosis as matrix mineralizes and nutrients can no longer reach the chondrocytes (cartilage is avascular!)
before they die chondrocytes secrete matrix metalloproteinases to degrade ECM, blood vessels invade remaining space. This brings osteoblasts/clasts which can secrete osteoid

59
Q

describe what the epiphyseal plate does

A

composed of 5 zones of cells and activity. cartilage formed towards epiphyseal side of plate. Cartilage is ossified towards diaphyseal side to lengthen bone

60
Q

reserve/resting zone

A

chondrocytes anchor plate to osseous tissue of epiphysis

61
Q

proliferation zone

A

chondrocytes proliferate

62
Q

hypertrophic cartilage zone

A

chondrocytes increase in size, accumulate alkaline phosphatase

63
Q

zone of calcification of cartilage

A

chondrocytes apoptose; cartilaginous matrix begins to calcify

64
Q

zone of ossification

A

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

65
Q

appositional growth

A

bone diameter increases, occurs in all bones

66
Q

when does appositional growth happen

A

when longitudinal growth stops

67
Q

how does appositional growth happen

A

osteoclats resorb old bone that lines the medullary cavity
meanwhile osteoblasts delivered via blood vessels produce new bone tissue beneath periosteum (intramembranous ossification)
subperiosteal cortical bone forms and an increase in bone diameter results

68
Q

appendicular skeleton components

A

4 bones in shoulder girdle, all the limbs and pelvis

69
Q

achondroplasia

A

most common form of skeletal dysplasia
AD
related to FGF receptor 3 mutation
primarily affects endochondral ossification in long bones and formation of base of skull

70
Q

symptoms of achondroplasia

A

short limbs and fingers
large skull
small mid face
prominent forehead

71
Q

marfan syndrome

A

form of skeletal dysplasia related to fibrillin 1 gene mutation

72
Q

symptoms of marfan syndrome

A 
long limbs 
long face
skeletal defects
dilation an dissection of ascending aorta
lens dislocation
73
Q

congenital hyperpituitarism

A

production of excess growth hormone
growth of soft tissues (enlargement of face) an bones of hands and feet: acromegaly
gigantism

74
Q

hypopituitarism

A 
growth hormone affected; short stature
normal arm and leg length
fat around waist and face
delated teeth development
sluggish hair growth
75
Q

congenital rickets

A

caused by severe vitamin D deficiency
rarely in utero
results in defective mineralization of cartilagenous growth plates

76
Q

osteogenesis imperfecta

A

brittle bone disease
hypomineralization of long bones of limbs leading to improper bones forming
90% linked to defects in COL1A1 or COL1A2 leading to reduced type 1 collagen production and altered bone matrix

77
Q

symptoms of OI

A

frequent and multiple fracturesl bowing of long bones and or curvature of spine can result in short stature
additional AEs on skin, muscle, joints, teeth, hearing, blue sclera may be observed

MM3 Leesy (12 decks)

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