Bone Flashcards
4 bone matrix proteins made by osteoblasts
- type I collagen
- alkaline phosphatase
- osteopontin and osteocalcin
2 enzymes produced by osteoclasts
- cathepsin k
- tartrate resistant acid phosphatase (TRAP)
origin of osteoclast
hematopeietic origin
2 structural features of osteoclasts
multinucleated and ruffled border
what is diploe
spongy bone in skull separating inner and outer compact bone
whats a lacuna
space in lamella where osteoctye resides
whats an osteoid?
the unmineralized organic component of bone
whats an osteocyte
a bone cell, formed when an osteoblast becomes embedded in the matrix it has secreted
how long before osteoid is mineralized
a few days
5 steps of long bone formation
- bone collar formation around hyaline cartilage model
- cavitiation of hyaline cartilage within cartilage model
- invasion of internal cavities by the periostial bud and spongy bone formation
- formation of medullary cavity as ossification continues; secondary ossification centers appear in epiphyses
- ossification of epiphyses
when ossification is completed where is cartilage found in the bone?
hyaline cartilage only in the epiphyseal plates and articular cartilages
5 zones of developing bone
- resting (quiescent) zone (outermost)
- growth (proliferation) zone
- hypertrophic zone
- calcification zone
- ossification (ostergenic) zone
how much of bone is organic matrix?
45-60%
what is primary protein of organic matrix of bone
Type I collagen
functions (4) of noncollagenous proteins of bone
- direct cell binding (osteoblasts/clasts)
- control spacial arrangement of mineral deposition
- control mineral nucleation
- control rates and sites of mineral resorption
osteonectin
Ca++ bindng protein
osteopontin
RGD protein
osteocalcin
- contains gamma carboxy glutamic acid
- needs vitamen D for production
- needs vit K for function
- produces binding site for calcium
- used as measure of osteoclastic metabolism
- restricted to bone
2 inhibitors of mineral deposition
pyrophosphate and magnesium
2 molecules that act as nucleation sites for mineral deposition
collagen and phosphoproteins
bisphosphonates inhibit what
osteoclast activity
what does phosphodiesterase do
inactivates intracellular second messangers (cAMP/cGMP)
where is PDE type 5 found
corpus cavernosum
side effects of hypercalcemia
- chronic
- lethargy, digestive tract abnormalities, possible cardiac arrythmias
- soft tissue calcificiation (cardiac valves/kidney tubules)
PTH function
- increase PLASMA Ca++
- increase Ca++ reabsorbtion by kidney and from bone
- increases 1,25-dihydroxy vitamen D
calcitonin function
causes Ca++ deposition in bone
vitamen D pathway from skin
- 7-dehydrocholesterol to
- colecalciferol (in skin) to
- 25-hydroxy vitamen D (in liver) to
- 1, 25-duhyroxy vitamen d D (in liver)
vitamen D action
increases Ca++ absorption
rickets symptoms
deficient growth of long bones
chronic hypocalcemia
expanded epiphyseal growth plate
bowing of legs
vitamen D deficiency and MS
decrease pro inflammatory cytokines
vitamen D deficiency and heart disease
inhibition of renin-angiotensin system
vitamen D deficiency and TB
resistance to mycobacteria
vitamen D deficiency and asthma
increase regulatory T cells
vitamen D deficiency and diabetes
increase in type II diabetes
vitamen D deficiency and cancer
increased apoptosis
deficiency of thyroid hormone during early development causes
cretinism
laron dwarfism
lack of GH receptors
mutations in IGF-1 receptor
no treatment
issues with HRT with estrogen for osteoporosis
increased CVS and memory problems
prostaglandins cause what
stimulate bone resorbtion
(since part of signalling pathway for PTH)
not detected in circulation
PTHrP involved with what
hypercalcemia of malignancy
what does TGF beta stimulate
matrix protein synthesis (esp collagen)
PDGF function
possible role in fracture repair b/c present in high concentration in bone
IGF1 stimulated by what
growth hormone (PTH)
IL 1
inflammatory mediator (involved in bone resorbtion)
- catabolin (cartilage degredaton)
- endogenous pyrogen (fever)
- LAF
- aka OAF
how does estogen stop osteoporosis
estrogen inhibits inflammatory mediator synthesis (osteoblasts can produce IL-1, IL-6, TNF alpha)
regulatory relationship between OB and OC
OB produce RANKL which binds to RANK on membrane of osteoclast precursor cells, stimulating differentaion of osteoclasts
what heavy metal causes brittle bones
cadmium
zinc deficiency causes
late onset of puberty and short stature
Cu++ deficiencty
weak CT matrices (aortic rupture) also weak bone structure
apical ectodermal ridge
responsible for growth of length of limb
zone of polarizing activity
responsible for finger to thumb axis of developing limb (ie. order of fingers on hand)
mediated via sonic hedgehog protein
mesenchyme differentiation based on cell density
low: fibrogenic
high: chondrogenic
mesenchyme differentiation based on oxygen tension
low: chondogenic
high: bone formation
bone membrane
bone lining cells cover bone surface with unknown function
3 types of circulating calcium and abundance
- ionized (50%)
- protein bound (esp albumin)
- complexed (like in phosphate or citrate)
where does degredation of PTH occur
liver and kidney
vit D3 AKA
cholecalciferol
what step in vit D formation is tightly regulated?
25-OH vit D to 1,25-(OH)2 vit D
effects of vit D toxicity
hypercalcemia and soft tissue calcification
Mechanism of OC response to PTH
NO pth receptors on OC
instead OC respond to secreted products of PTH stimulated OB
cathepsins function
degrade collagen in an acidic environment
back of hand to palm formation controlled by
En-1, Wnt7a, Lmx-1
