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Chok Biochem 4th Shift Reviewer Bone

Chok Biochem 4th Shift Reviewer Bone

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Published by: Gaka on Aug 14, 2010
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BONE METABOLISM
Types of Bone
Cortical / Compact
most shafts of long bones, Haversian systems
Trabecular / Spongy
most vertebral bodies and ends of long bones, greater surface area, remodelved more rapidly,lamellae run parallel to bone surface
BoneExtracellular Matrix 
Organic portion
type I collagen, ground substance = proteoglycans (keratin sulfate, chondroitin sulfate, hyaluronic acid
Inorganic portionhydroxyapatite
(Ca
10
(PO
4
)
6
(OH)
2
)
BoneProteins
Type I collagen
major protein, 90-95% of organic material
Type V collagen
small amounts (10%)
Bone Specific Proteins
CS-PG III, osteocalcin, bone sialoprotein, BMP
Non-collagen proteinsTRAMP
Tyrosine-rich acidic matrix protein
Enzymes
For collagen synthesis
Major bonecells
Osteoblasts
mononuclear,
mesenchymal
precursors, depiosit new bone matrix (osteoid), becomes osteocytes,control mineralization by regulating passage of Ca and PO4 ions across membranes, synthesize TypeI collagen, growth factors, cytokines
Osteoclasts
multinucleated, from
pluripotent hematopoietic
 
stem cells
,
resorb
bone tissue via lysosomes andH+ (via carbonic anhydrase) to resorb bone mineral at the ruffled border 
Osteocytes
connect with one another and lining cells on bone surface via cytoplasmic processes, running thoughcanaliculi,
sensors
of mechanical strain, release signaling molecules (PGE, NO)
Factors for bonemineralization
Alkaline phosphatase
unclear role
Matrix vesicles at sites of mineralization
unclear role
Type I collagen
necessary
Acidic phosphoproteins(bone sialoprotein)
Poly Asp/Glu bind Ca, provide initial scaffold
Certain proteoglycans &glycoproteins
inhibit nucleation
OC formationand Differentiation
PU-Iinitial
OC and monocyte differentiation
C-fos, NFkB
differentiation of committed precursors to mature OC
M-CSF
OC and macrophage differentiation
RANKL, RANK
promote differentiation of precursors to OC
C-srclacuna
formation
Osteoprotegerininhibits
OC formation
MoleculesRegulating Osteoclast activity 
Carbonic anhydrase II
formation of 
H+
within osteoclasts
TCIRGIencodes
subunit of osteoclast proton pump
Cathepsin Kdegrades
collagen and other proteins
OB formationand Differentiation
CBFA1
regulatory molecule in pre-OB,
key trigger for differentiation
, activates coordinated gene expressioncharacteristic of OB phenotype
Osterixtranscription facto
for differentiation of mesenchymal cells into OB
Sclerostin
secretin protein, binds bone morphogenic proteins, promote bone formation by
stimulating OBprecursor growth
and differentiation
Factors affecting OC & OB
OC 
OC 
OB
OB
PTH, Vit DcorticosteroidsPTH, Vit DCalcitonin, estrogen
Calcium Metabolism
Occurrence:
most abundant, 1.5-2% of body weight, 39% of total body minerals, 99% in bone and teeth, 1% in blood, ECF and soft tissues
Distribution:
Non-exchangeable pool
– stable, unavailable for short-term regulation;
o
Exchangeable pool
– 1% involved in metabolic activities, 600-700 mg exchanged daily
Total serum Ca
: 8-8-10.8 mg/dL =
Free/ionized
– 50%,
Anion bound
to PO4, HCO3, citrate – 5%,
Bound to albumin
or globulin – 45%
 Absorption and utilization
– mainly
duodenum
, 20-30% of ingested,
VitD requiring
, absorbable if 
water-soluble
, unabsorbed is excreted
Routes of Intestinal Calcium Absorption
Transcellular 
(active, saturable, proximal duodenum, vitD-dependent Ca BP (calbindin)),
Paracellular 
(passive, nonsaturable, vitD independent, throughout small intestine, diet-dependent)
Factors affecting Absorption
Increase AbsorptionDecrease Absorption
Greater need, small supply, growth, pregnancy, lactation, deficiency,exercise, active VitD, acidic, lactose w/ normal lactase supply, moderate fatVitD deficiency, oxalic / phytic acid (binds with Ca
insoluble), fiber,alkaline medium, excessive GI motility, stress, medications, aging
Calcium BalanceSourceTakes from ECFGives to EC
Bone
0.50.5
Intestine
0.20.2, excretes 0.8
Kidney
10.0, excretes 0.29.8
Roles of PTH, Calcitonin and Vit DStimuliEffec
PTH
↓ Ca↑ Ca (↑ resorption, ↓ excretion), Vit D
Calcitonin
CaCa (resorption)
Vit D
PTH↑ Ca absorption, ↑ Ca resorption
Metabolic / Genetic Diseases
Dwarfism
?
Rickets
↓ Vit D, children
Osteomalacia
↓ Vit D, adults
Hyperparathyroidism
?
Osteogenesis Imperfecta
Mutated collagen (COL1A1, COL1A2)
Osteoporosis
Hereditary, postmenopausal, collagen mutation, Vit D receptor gene

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