bone mineral chemistry and structure
TRANSCRIPT
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Bone Mineral Chemistry and Structure
JC Elliott, QMUL
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1) General composition of bone2) Variability of composition of calcium
phosphate in mineralised tissues3) Identity of calcium phosphate in bone4) Explanation of variable composition-
structure of mineral5) Removal of mineral6) Formation of mineral
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Importance of chemistry and structure of inorganiccomponent of bone
1) Bone mineral acts as store of essential ions2) It acts as a long term buffer against acids3) Can accumulate toxic metals4) To understand mechanical properties of bone5) To understand mineralisation and resorptionprocesses
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Composition of Bone (wt % of whole tissue)
Inorganic 70Organic 22Water remainder
Inorganic is a calcium phosphateOrganic is mainly collagen
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Composition of inorganic (wt % of whole tissue)
Ca 26PO4 34CO3 7Na 0.9Mg 0.7K 0.3H2O 3-6?
Composition is variablee.g. CO3 falls in metabolic acidosis
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Size of crystals in bone
Much too small to see in light microscope!
Electron microscope shows they are mainlyplates approx 40nm long×20nm widevery thin
A Ca atom is about 1/5 nm across
Consequence of small size is crystals have largereactive surface area
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Overall composition is deceptiveLook at anatomical and temporal variations
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Changes in bone mineral with age of mineral
Young ----------------------------- Old
High CO3& acid phosphate Changes towardsCa10(PO4)6(OH)2
Low OH- & “crystallinity” Better crystallised
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Identity of calcium phosphate in bones and teeth
Ca3(PO4)2 tricalcium orthophosphateCaHPO4 monetiteCaHPO4.2H2O brushiteCa8H2(PO4)6.5H2O octacalciumphosphateCa10(PO4)6(OH)2 hydroxyapatite
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Chemical composition approximates toCa10(PO4)6(OH)2, hydroxyapatite
X-ray diffraction like hydroxyapatite
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Composition of inorganic (wt % of whole tissue)Ca 26PO4 34CO3 7Na 0.9Mg 0.7K 0.3H2O 3-6?+…+
Composition is variablee.g. CO3 falls in metabolic acidosis
Inconsistent with hydroxyapatite
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Need to look at structure of hydroxyapatite
Look at ball and spoke model
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Size of ions in hydroxyapatite
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Approximate PO43- ion as a sphere
Apatite is approximately hexagonalclose-packed spheres
Other ions (Ca2+, OH-) go is spaces between spheres
Result: apatite very stable and tolerant of differentsized ions: many ionic substitutions are possible
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Substitutions in biological apatites
Ca2+ Sr2+, Pb2+, Na+, vacancyPO4
3- HPO42-, CO3
2-
OH- F-, Cl-, H2O, CO32-(limited)
Substitutions can be combined, butcharge balance must be maintained
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Many ions can also be adsorbed on thelarge surface area of the bone crystals
In summary, variable composition is explained by:1) Replacing ions in the crystals2) Adsorbing ions on crystal surfaces
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Resorption and mineralisation
Dissolution and precipitation of mineral
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Resorption
Ca10(PO4)6(OH)2 + 2H+ --- 10Ca2+ + 6PO43- + 2H2O
acid
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Mineralisation
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Biomineralisation
Key to understanding the problem is that extracellular fluid is supersaturated with respect to hydroxyapatite
Problems:1) How do we nucleate the crystals?2) How do we stop the crystal growth?3) How is their orientation controlled?
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Role of collagen
In the 1960’s, electron microscope studies showedthat the initial crystals of hydroxyapatite were associated with the cross-banding regions of collagenand X-ray diffraction showed that the hexagonal axis(long direction) of the crystals were parallel to the collagen fibres
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Collagen continued
It was therefore suggested that collagen was responsiblefor the nucleation and orientation of the hydroxyapatitecrystals
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Collagen continued(1970’s)
Big problem:Why does some collagen mineralise,whilst other identical collagen does not?
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Epitaxial role of collagen has been subsequentlydeveloped by the finding that nucleation in vitro can be enhanced by certain peptides e.g. osteonectinOthers cause inhibition of crystal growth.
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Molecules Associated with Calcifying Tissues
CollagenType I present in bone, dentine and cementum, but not enamel. Also present in many tissues that do not calcify.
Non-collagenous proteinsOccur in bone and dentine matrices and are mainly acidic phosphoproteins. The bind Ca and also bind to collagen. Might be a candidate for initiation of mineralisation when bound to collagen. This group also includes the gamma-carboxyglutamate-containing proteins (GLA proteins), osteonectin, osteopontin and bone sialoprotein.
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Molecules associated with calcifying tissues (continued)
ProteoglycansThere is a clear association between proteoglycans and apatite crystals when bone mineralisation takes place in cartilage. However, the proteoglycan content in the cartilage falls during bone formation.
LipidsSince 1959, it is known that they occur at the developing front of mineralisation in bone. Their role is unclear.
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Matrix vesiclesFirst described in calcifying cartilage in 1967. Also in bone, cementum and reparative dentine. About 100 nm in diam. When they bud off, the accumulate Ca and PO4. Calcification begins on the internal surface of the membrane, often with a single crystal inside. The vesicle increases in size and ruptures, releasing crystals.
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Further reading:
Biomineralization, Principles and Concepts in BioinorganicMaterials Chemistry. Stephan Mann, Oxford Univ Press, 2001
On Biomineralization. HA Lowenstam and Stephen Weiner,Oxford Univ Press, 1989
Biomineralization, Chemical and Biochemical PerspectivesS Mann, J Webb and RJP Williams (eds)VCH Verlagsgesellschaft, Weinheim, Germany, 1989
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Ca10(PO4)6(OH)2 + 2F- ----> Ca10(PO4)6F2
At higher F- ion concentrations:
Ca10(PO4)6(OH)2 + 20F- ----> 10CaF2 + 6PO43- + 2OH-
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Ca10(PO4)6(OH)2
Ca10-x(HPO4)x(PO4)6-x(OH)2-x