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Chok Biochem 4th Shift Reviewer Bone

Chok Biochem 4th Shift Reviewer Bone

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03/18/2014

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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

Bone
Extracellular
Matrix

Organic portion
type I collagen, ground substance = proteoglycans (keratin sulfate, chondroitin sulfate, hyaluronic acid
Inorganic portion
hydroxyapatite(Ca10(PO4)6(OH)2)
Bone
Proteins
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 proteins
TRAMP
Tyrosine-rich acidic matrix protein
Enzymes
For collagen synthesis
Major bone
cells
Osteoblasts

mononuclear,mesen ch ymal precursors, depiosit new bone matrix (osteoid), becomes osteocytes,
control mineralization by regulating passage of Ca and PO4 ions across membranes, synthesize Type I
collagen, growth factors, cytokines

Osteoclasts
multinucleated, from pluripotent hematopoietic stem cells,resorb bone tissue via lysosomes and
H+ (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 though
canaliculi,sensors of mechanical strain, release signaling molecules (PGE, NO)

Factors for
bone
mineralizatio
n

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 formation
and
Differentiatio
n

PU-I
initial 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-src
lacunaformation
Osteoprotegerin
inhibits OC formation

Molecules
Regulating
Osteoclast
activity

Carbonic anhydrase II
formation ofH+ within osteoclasts
TCIRGI
encodes subunit of osteoclast proton pump
Cathepsin K
degrades collagen and other proteins

OB formation
and
Differentiatio
n

CBFA1
regulatory molecule in pre-OB, key trigger for differentiation, activates coordinated gene expression
characteristic of OB phenotype
Osterix
transcription factor for differentiation of mesenchymal cells into OB
Sclerostin
secretin protein, binds bone morphogenic proteins, promote bone formation by stimulating OB
precursor growth and differentiation
\ue000
Factors affecting OC & OB
\u2191 OC
\u2193 OC
\u2191 OB
\u2193 OB
PTH, Vit D
corticosteroids
PTH, Vit D
Calcitonin, estrogen
Calcium Metabolism
\ue000
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
\ue000
Distribution:Non-exchangeable pool \u2013 stable, unavailable for short-term regulation;
o
Exchangeable pool \u2013 1% involved in metabolic activities, 600-700 mg exchanged daily
\ue000
Total serum Ca: 8-8-10.8 mg/dL =Free/ionized \u2013 50%, Anion bound to PO4, HCO3, citrate \u2013 5%, Bound to albumin or globulin \u2013 45%
\ue000
Absorption and utilization \u2013 mainlyduode num, 20-30% of ingested, VitD requiring, absorbable ifw ater-soluble, unabsorbed is excreted
\ue000
Routes of Intestinal Calcium Absorption \u2013Tr ansc e llula r (active, saturable, proximal duodenum, vitD-dependent Ca BP (calbindin)),
Paracellular (passive, nonsaturable, vitD independent, throughout small intestine, diet-dependent)
\ue000
Factors affecting Absorption
Increase Absorption
Decrease Absorption
Greater need, small supply, growth, pregnancy, lactation, deficiency,
exercise, active VitD, acidic, lactose w/ normal lactase supply, moderate fat
VitD deficiency, oxalic / phytic acid (binds with Ca\ue001 insoluble), fiber,
alkaline medium, excessive GI motility, stress, medications, aging
\ue000
Calcium Balance
Source
Takes from ECF
Gives to ECF
Bone
0.5
0.5
Intestine
0.2
0.2, excretes 0.8
Kidney
10.0, excretes 0.2
9.8
\ue000
Roles of PTH, Calcitonin and Vit D
Stimuli
Effect
PTH
\u2193 Ca
\u2191 Ca (\u2191 resorption, \u2193 excretion), Vit D
Calcitonin
\u2191 Ca
\u2193 Ca (\u2193 resorption)
Vit D
PTH
\u2191 Ca absorption, \u2191 Ca resorption
Metabolic / Genetic Diseases
Dwarfism
?
Rickets
\u2193 Vit D, children
Osteomalacia
\u2193 Vit D, adults
Hyperparathyroidism
?
Osteogenesis Imperfecta
Mutated collagen (COL1A1, COL1A2)
Osteoporosis
Hereditary, postmenopausal, collagen mutation, Vit D receptor gene

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