Bone Cell Biology Flashcards

1
Q

cells in bone

A

osteoblasts, osteocytes, osteoclasts

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2
Q

osteoclasts activated/inhibited by?

A

activated by PTH, inhibited by calcitonin

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3
Q

inorganic bone matrix

A

70%, Ca + phosphorus = hydroxyapatite

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4
Q

organic bone matrix

A

osteoid. type 1 collagen, proteoglycans, glycoproteins

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5
Q

osteocalcin

A

bone specific gene

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6
Q

osteoblast specific genes

A

cbfa-1, osteoclacin

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7
Q

growth factors that induce osteoblast differentiation

A

bone morphogenetic proteins

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8
Q

osteoid

A

made by osteoblasts. type 1 collagen & glycoproteins

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9
Q

osteocytes

A

occupy lacunae between lamellae of bone matrix. 1 per lacuna.

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10
Q

osteocyte function

A

maintain bone matrix, join processes of other osteocytes thru matrix via gap junctions

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11
Q

osteoclasts

A

destroy/remodel bone matrix, multinuclear (from fused macrophages), reside in Howship’s lacunae

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12
Q

what microenvironment promotes bone resorption?

A

ruffled border of the osteoclast, attaches to ECM

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13
Q

calcitonin’s effect on osteoclasts

A

inhibits osteoclasts

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14
Q

PTH’s effect on osteoclasts

A

activates osteoclasts, causes lysosomes to release cathepsin K into microenvironment. becomes more acidic.

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15
Q

outer layer of CT

A

periosteum

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16
Q

inner layer of CT

A

endosteum

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17
Q

osteoblast location

A

in periosteum, fewer in endosteum

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18
Q

osteocytes location

A

within lacunae of bony matrix, btwn periosteum and endosteum

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19
Q

osteoclasts loction

A

attached to bony matrix on endosteal side

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20
Q

cortical bone

A

compact, dense, no cavitation, on outside (osteon)

21
Q

trabecular bone

A

spongy, inside endosteum, cancellous (osteocytes)

22
Q

flat bones

A

2 plates of compact one surround diploe of spongy bone

23
Q

long bones

A

diaphysis (shaft), epiphyses (ends)

24
Q

osteons

A

cylinder with concentric lamellae

25
Q

lamellae

A

contain lacunae, those harbor osteocytes, intercommunicate via canaliculi

26
Q

haversian canal

A

surrounded by inntermost lamella. long axis, contains BVs, nerves & lymph

27
Q

volkmann’s canals

A

run perpendicular to haversian canals. also contain BVs, nerves and lymph

28
Q

bone development (2 ways)

A
  1. intramembranous (embryonic, osteoblasts deposit osteoid onto mesoderm)
  2. endochondral (osteoblasts deposit osteoid onto cartilage)
29
Q

endochondral process

A

bone forms on hyaline cartilage. @ diaphysis, osteoblasts invade calcified cartilage, secrete osteoid on it and cause ossification. same @ epiphyses but there articular cartilage remains @ ends, and epiphyseal plate cartilage also remains for growth in length

30
Q

what hormone stimulation signals for bones to “grow long”

A

sex steroid hormone–> pituitary–>growth hormone (GH; somatotropin)–>liver–>somatomedin (IGF-I)–>epiphyseal plate

31
Q

zones of bone growth and their inductors

A

zone of proliferation: induced by somatomedin (IGF-I)

zone of hypertrophy: 20% of fractures (hollow)

zone of calcification (calcified cartilage): collagen X, NOT collagen II (stains blue)

zone of ossification: eosinophilic due to deposition of collagen I by osteoblasts

32
Q

fracture repair process

A
  1. macrophages remove debris
  2. chondroblasts secrete a callus of hyaline cartilage
  3. osteoblasts replace cartilaginous callus with bony callus
  4. primary bone is replaced by lamellar secondary bone
33
Q

what is sometimes require for repairing difficult fractures? what is in the “pipeline”?

A

grafting (450,000/year in US)-some don’t heal; patients lack good bone

in pipeline: bone morphogenetic proteins (BMP-2 and BMP-7); adult stem cells (MSCs) to become osteoblasts; growth factors or cells, or both, are implanted within biodegradable ‘sponges’ made of collagen I

34
Q

remodeling never stops…what is the general process of remodeling?

A

osteoclasts excavate bone which is then replaced by activated osteoblasts

35
Q

osteopetrosis

A

dense heavy bone; osteoclasts lack ruffled border

36
Q

osteoporosis

A

resorption by osteoclasts outpaces osteogenesis=hollow fragile bones
~30 mil americans, 2/3 women (post-menopausal women lose ~2% bone mass annually)
treatable
breaks at wrist, hip, spine

37
Q

prevention of osteoporosis

A

dietary Ca++, vitamin D (improves absorption of Ca++); weight bearing exercises

38
Q

screening for osteoporosis

A

bone mineral density (BMD; grams/cm2)
compare BMD with “young-normal” subjects
every 2-5 years. look at T score (# of std dev BMD is below young-normal mean)

39
Q

therapeutic targets for osteoporosis treatments

A

would want to inhibit osteoclasts and activate osteoblasts

40
Q

osteoclast production

A

stromal cells in bone marrow are induced by PTH to secrete 3 factors that regulate osteoclasts: RANKL, OPG, and M-CSF, which act on macrophages

41
Q

M-CSF (macrophage colony-stimulating factor)

A

induces macrophage proliferation

42
Q

RANK-L (receptor for activator of nuclear factor-kb ligand)

A

induces macrophage differentiation into osteoclasts

43
Q

OPG (osteoprotegerin)

A

osteoprotegerin antagonizes RANK-L by binding to its receptor

44
Q

a5B3

A

an integrin, enables osteoclasts to bind to ruffled border

45
Q

osteoblast inhibition & induction

A

inhibited by leptin, induced by BMP, induced by PTH (increased concentration spike)

46
Q

osteoclasts inhibition & induction

A

inhibited by clacitonin, osteoprotegerin, induced by RANK-L, induced by PTH (@ constant levels)

47
Q

effect of anabolic drugs on osteoblasts

A

pro-osteoblast. ex: PTH 1-34 (injection causes increase in PTH spikes favoring osteoblast production

48
Q

effect of anti-resorptive drugs on osteoclasts

A

anti-osteoclast. ex: SERMS (raloxifene), bisphosphonates (Boniva), calcitonin

49
Q

drugs in pipeline?

A

drugs with more specificity. e.g. OPG to inhibit osteoclasts, anabolic agents like CBFA-1, anti-a5B3 to inhibit binding of osteoclasts to matrix