Bone Cell Biology

Question 1

cells in bone

Answer 1

osteoblasts, osteocytes, osteoclasts

Question 2

osteoclasts activated/inhibited by?

Answer 2

activated by PTH, inhibited by calcitonin

Question 3

inorganic bone matrix

Answer 3

70%, Ca + phosphorus = hydroxyapatite

Question 4

organic bone matrix

Answer 4

osteoid. type 1 collagen, proteoglycans, glycoproteins

Question 5

osteocalcin

Answer 5

bone specific gene

Question 6

osteoblast specific genes

Answer 6

cbfa-1, osteoclacin

Question 7

growth factors that induce osteoblast differentiation

Answer 7

bone morphogenetic proteins

Question 8

osteoid

Answer 8

made by osteoblasts. type 1 collagen & glycoproteins

Question 9

osteocytes

Answer 9

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

Question 10

osteocyte function

Answer 10

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

Question 11

osteoclasts

Answer 11

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

Question 12

what microenvironment promotes bone resorption?

Answer 12

ruffled border of the osteoclast, attaches to ECM

Question 13

calcitonin’s effect on osteoclasts

Answer 13

inhibits osteoclasts

Question 14

PTH’s effect on osteoclasts

Answer 14

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

Question 15

outer layer of CT

Answer 15

periosteum

Question 16

inner layer of CT

Answer 16

endosteum

Question 17

osteoblast location

Answer 17

in periosteum, fewer in endosteum

Question 18

osteocytes location

Answer 18

within lacunae of bony matrix, btwn periosteum and endosteum

Question 19

osteoclasts loction

Answer 19

attached to bony matrix on endosteal side

Question 20

cortical bone

Answer 20

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

Question 21

trabecular bone

Answer 21

spongy, inside endosteum, cancellous (osteocytes)

Question 22

flat bones

Answer 22

2 plates of compact one surround diploe of spongy bone

Question 23

long bones

Answer 23

diaphysis (shaft), epiphyses (ends)

Question 24

osteons

Answer 24

cylinder with concentric lamellae

Question 25

lamellae

Answer 25

contain lacunae, those harbor osteocytes, intercommunicate via canaliculi

Question 26

haversian canal

Answer 26

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

Question 27

volkmann's canals

Answer 27

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

Question 28

bone development (2 ways)

Answer 28

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

Question 29

endochondral process

Answer 29

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

Question 30

what hormone stimulation signals for bones to "grow long"

Answer 30

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

Question 31

zones of bone growth and their inductors

Answer 31

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

Question 32

fracture repair process

Answer 32

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

Question 33

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

Answer 33

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

Question 34

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

Answer 34

osteoclasts excavate bone which is then replaced by activated osteoblasts

Question 35

osteopetrosis

Answer 35

dense heavy bone; osteoclasts lack ruffled border

Question 36

osteoporosis

Answer 36

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

Question 37

prevention of osteoporosis

Answer 37

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

Question 38

screening for osteoporosis

Answer 38

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)

Question 39

therapeutic targets for osteoporosis treatments

Answer 39

would want to inhibit osteoclasts and activate osteoblasts

Question 40

osteoclast production

Answer 40

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

Question 41

M-CSF (macrophage colony-stimulating factor)

Answer 41

induces macrophage proliferation

Question 42

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

Answer 42

induces macrophage differentiation into osteoclasts

Question 43

OPG (osteoprotegerin)

Answer 43

osteoprotegerin antagonizes RANK-L by binding to its receptor

Question 44

a5B3

Answer 44

an integrin, enables osteoclasts to bind to ruffled border

Question 45

osteoblast inhibition & induction

Answer 45

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

Question 46

osteoclasts inhibition & induction

Answer 46

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

Question 47

effect of anabolic drugs on osteoblasts

Answer 47

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

Question 48

effect of anti-resorptive drugs on osteoclasts

Answer 48

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

Question 49

drugs in pipeline?

Answer 49

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