Bone Cell Biology Flashcards
cells in bone
osteoblasts, osteocytes, osteoclasts
osteoclasts activated/inhibited by?
activated by PTH, inhibited by calcitonin
inorganic bone matrix
70%, Ca + phosphorus = hydroxyapatite
organic bone matrix
osteoid. type 1 collagen, proteoglycans, glycoproteins
osteocalcin
bone specific gene
osteoblast specific genes
cbfa-1, osteoclacin
growth factors that induce osteoblast differentiation
bone morphogenetic proteins
osteoid
made by osteoblasts. type 1 collagen & glycoproteins
osteocytes
occupy lacunae between lamellae of bone matrix. 1 per lacuna.
osteocyte function
maintain bone matrix, join processes of other osteocytes thru matrix via gap junctions
osteoclasts
destroy/remodel bone matrix, multinuclear (from fused macrophages), reside in Howship’s lacunae
what microenvironment promotes bone resorption?
ruffled border of the osteoclast, attaches to ECM
calcitonin’s effect on osteoclasts
inhibits osteoclasts
PTH’s effect on osteoclasts
activates osteoclasts, causes lysosomes to release cathepsin K into microenvironment. becomes more acidic.
outer layer of CT
periosteum
inner layer of CT
endosteum
osteoblast location
in periosteum, fewer in endosteum
osteocytes location
within lacunae of bony matrix, btwn periosteum and endosteum
osteoclasts loction
attached to bony matrix on endosteal side
cortical bone
compact, dense, no cavitation, on outside (osteon)
trabecular bone
spongy, inside endosteum, cancellous (osteocytes)
flat bones
2 plates of compact one surround diploe of spongy bone
long bones
diaphysis (shaft), epiphyses (ends)
osteons
cylinder with concentric lamellae
lamellae
contain lacunae, those harbor osteocytes, intercommunicate via canaliculi
haversian canal
surrounded by inntermost lamella. long axis, contains BVs, nerves & lymph
volkmann’s canals
run perpendicular to haversian canals. also contain BVs, nerves and lymph
bone development (2 ways)
- intramembranous (embryonic, osteoblasts deposit osteoid onto mesoderm)
- endochondral (osteoblasts deposit osteoid onto cartilage)
endochondral process
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
what hormone stimulation signals for bones to “grow long”
sex steroid hormone–> pituitary–>growth hormone (GH; somatotropin)–>liver–>somatomedin (IGF-I)–>epiphyseal plate
zones of bone growth and their inductors
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
fracture repair process
- macrophages remove debris
- chondroblasts secrete a callus of hyaline cartilage
- osteoblasts replace cartilaginous callus with bony callus
- primary bone is replaced by lamellar secondary bone
what is sometimes require for repairing difficult fractures? what is in the “pipeline”?
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
remodeling never stops…what is the general process of remodeling?
osteoclasts excavate bone which is then replaced by activated osteoblasts
osteopetrosis
dense heavy bone; osteoclasts lack ruffled border
osteoporosis
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
prevention of osteoporosis
dietary Ca++, vitamin D (improves absorption of Ca++); weight bearing exercises
screening for osteoporosis
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)
therapeutic targets for osteoporosis treatments
would want to inhibit osteoclasts and activate osteoblasts
osteoclast production
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
M-CSF (macrophage colony-stimulating factor)
induces macrophage proliferation
RANK-L (receptor for activator of nuclear factor-kb ligand)
induces macrophage differentiation into osteoclasts
OPG (osteoprotegerin)
osteoprotegerin antagonizes RANK-L by binding to its receptor
a5B3
an integrin, enables osteoclasts to bind to ruffled border
osteoblast inhibition & induction
inhibited by leptin, induced by BMP, induced by PTH (increased concentration spike)
osteoclasts inhibition & induction
inhibited by clacitonin, osteoprotegerin, induced by RANK-L, induced by PTH (@ constant levels)
effect of anabolic drugs on osteoblasts
pro-osteoblast. ex: PTH 1-34 (injection causes increase in PTH spikes favoring osteoblast production
effect of anti-resorptive drugs on osteoclasts
anti-osteoclast. ex: SERMS (raloxifene), bisphosphonates (Boniva), calcitonin
drugs in pipeline?
drugs with more specificity. e.g. OPG to inhibit osteoclasts, anabolic agents like CBFA-1, anti-a5B3 to inhibit binding of osteoclasts to matrix
