Calcium and Bones

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Calcium and Bones Endocrine Controls
Calcium homeostasis is important because the ion
is needed to maintain nerve muscle function
to control many cellular activities in virtually
all cells. It is also a major structural
component of the body in both the bone
extracellular compartments. The hormones
involved in calcium metabolism in general in
bone in particular include the protein
parathyroid hormone the modified steroid
calcitriol (1a,25 dihydroxy vitamin D3 1a,25
dihydroxycholecalciferol), which both promote the
movement of calcium ion into circulation, the
counter-balancing protein hormone calcitonin,
which promotes a decrease in circulating calcium.

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Parathyroid hormone (PTH), an 84 amino acid-long
protein, is produced by processing of a longer
translation product by the parathyroid glands
which are embedded in the thyroid tissues in many
vertebrate species. Calcitonin, a 32 amino
acid-long peptide is produced by the
parafollicular or C cells of the thyroid
interstitium these cells do not play a role in
thyroid hormone production.
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Calcitriol is derived from a metabolite of
cholesterol, 7-dehydro-cholesterol formed in the
liver. Non-ezymatic breakage of the B-ring by
ultraviolet light exposure in the skin form
cholecalciferol (vitamin D3) which may also be
obtained in the diet, e.g., in vitamin D
fortified milk. Liver hydroxylates
chole-calciferol on the sidechain to form
25-hydroxycholecalciferol which is carried by the
vitamin D carrier protein in serum to the kidney.
In the kidney the molecule can be hydroxylated
once or twice more to form the active hormone
calcitriol or the inactive metabolites
24,25-dihydroxycholecalciferol or 1a, 24,
25-trihydroxycholecalciferol. PTH promotes 1a
hydroxylation activation, CT promotes 24
hydroxylation inactivation.
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Bone is a complex tissue including inorganic,
organic, cellular components. The major
inorganic component is hydroxyapatite a complex
calcium salt including phosphate, carbonate,
magnesium, other ions. This is sensitive to
attack by acid forms about 2/3 of the weight of
bone. It can serve as a reservoir of problematic
cations such as lead, radium, strontium, or
arsenic making effects of exposure more prolonged
than if the ions were always free in circulation.
Hydroxyapatie is interweaved with organic
components such as collagens many minor protein
contributors. The cellular players are thought
to be derived from blood-lineage stem cells.
They include osteoblasts that cover the surface
of bone help deposit bone mineral osteocytes,
also bone builders, which occupy interior
locations in bone that eventually are walled off
by mineral deposition osteoclasts, large
multinucleate cells, which are probably modified
macrophages, that act to break down remodel
bone. Other cells include vascular endothelial
cells in blood vessels nerves.
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A sketch of a cross section of long bone near the
epiphyses, growth plate, shows the various cells
involved in bone remodeling in relation to the
bone matrix.
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The major hormonal target for calcium homeostasis
in bone is the osteoclast which can mobilize Ca
by secreting acid proteolytic enzymes onto the
bone matrix surface in response to stimulation by
PTH calcitriol.
http//www.besthealth.com/besthealth/bodyguide/ref
text/images/osteoclast.jpg
CT blocks PTH (cAMP cascade) calcitriol
(nuclear receptor). Sex steroids modulate bone
cell activity androgen stimulates bone
deposition, lack of estradiol causes bone loss.
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Calcium ion movement across cells is shown. Note
that the cell forms are more typical of
osteoblasts which build bone and usually
transport calcium toward the matrix. An
osteoclast, as shown in the last two slides,
would emphasize degradation of bone mineral
matrix would pump calcium into the vasculature.
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