Biomineralization Flashcards
What percent of enamel is mineral?
99%
What percent of dentine is enamel?
70%
What is the purpose of organic components in mineralized tissues?
To provide scaffold and regulate process
What are the three organic components in mineralized tissues?
Collagen
Non-collagenous proteins
Proteoglycans
What is the mineral phase in mineralized tissues?
Calcium hydroxyapatite
What is enamel lacking that most other mineralized tissues have?
Collagen
In hydroxyapatite, apatite is based on what, rather than composition?
Structure, not composition
Is hydroxyapatite (HAP) a pure chemical compound?
Nope
What is a unit cell?
A conceptual entity representing the smallest section of a crystal
How many possible unit cells are there?
14
What is the lattice in crystals?
The pattern of repetition of the unit cells in a crystal
To which system of crystal structure do apatites belong?
hexagonal
What shape do naturally occurring hydroxyapaties form?
Hexagonal prisms and plate-like crystals
What is the shape of the hydroxyapatite lattice?
Triangular groups of 3 Ca located along c axis with each triangle rotated 60 degrees relative to the next layer
Where is the OH group found in a hydroxyapatite lattice?
In the center of the triangle, slightly above/below the plane
Why can’t two OH groups be oriented toward each other in hydroxyapatite lattices?
Space restrictions
What lies around each crystallite?
A hydration shell
What are the measurements of crystals in mesenchymal hard tissues?
150-400 angstroms long
50-100 angstroms wide
25-50 angstroms thick
What are the measurements of crystals in enamel?
1400 angstroms long
500-800 angstroms wide
250-300 angstroms thick
The small size of crystals in bond and dentin mean what?
They have enormous surface area
Biological apatites are ___ apatites.
Substituted
In hydroxyapatite crystals, Ca can be substituted for what ions?
Na Mg Pb Zn Cu
In hydroxyapatite crystals, PO4 can be substituted for what ions?
CO3
In hydroxyapatite crystals, OH can be substituted for what ions?
Fl
Cl
CO3
Apatites of normal bone, enamel and dentin are principally what type of apatites?
Type B carbonate apatites
Where do ions get absorbed or bound into the apatite crystal?
In the hydration layer
3-6% of phosphate groups in bones and teeth are replaced by what groups?
Carbonate groups
Substituting carbonate groups instead of phosphate groups in the hydroxyapatite crystals has what effects?
Increased solubility
More susceptible to acid dissolution
Favors caries
What part of the teeth has the least amount of carbonate, Mg and Na
Enamel
What effects does substituting fluoride into the crystals produce?
Larger crystals
Decreased solubility
Promotes lesion repair
Substituting fluoride in the apatite crystals minimizes the incorporation of what compound?
HPO4
Substituting fluoride in the apatite crystals minimizes the negative effects of what?
Other ions
ex. CO3
How many ions come together to form a unit cell? Do they do so spontaneously?
18
No
Other types of solids form from calcium and phosphate. Where are these solids usually found?
In pathological conditions
Ex. Whitelock
Salivary stones
What compound may be another intermediate which causes enamel to grow as long plates?
Octacalcium phosphate
What is the amount of total body calcium?
1000g
How many grams of calcium are found outside of bone?
12g
About how much of our dietary calcium is excreted?
90%
How much total body phosphate do we have?
700g
About how much phosphate is found in muscle?
50g
How much phosphate is found outside of bone?
100g
What is the main source of Ca and P for bone?
Serum
Where were the Ca and P ions that are incorporated in mineralized tissues found?
As free ions in body fluid
What is the main source of Ca and P for the remineralization of enamel?
Saliva
How are calcium and phosphate levels in biological fluids controlled?
Homeostatically
What is the function of parathyroid hormone?
Responds to low serum calcium
How does parathyroid hormone increase blood calcium levels?
By activating osteoclasts that direct bone resorption
What does calcitonin do?
Responds to high serum calcium levels
How does calcitonin reduce blood calcium levels?
Promotes bone formation by activating osteoblasts and inhibiting osteoclasts
Where does vitamin D promote calcium absorption?
In the GI tract
What concentration of intracellular calcium concentration trigger apoptosis?
Greater than 10^-6 M
What is the concentration of extracellular calcium?
About 10^-3
What are the salivary inhibitors of crystal growth?
Statherin
aPRPs
PPi
pH below ___ starts to dissolve enamel leading to white spots, and eventually caries.
5.2
Although tissue fluids and saliva are supersaturated in calcium and phosphate ions, does spontaneous precipitation of CaP products does not occur. Why not?
The energy barrier must be overcome for crystallization to occur
Inhibitors of crystal formation are present that raise the energy barrier
Intitial ioncluster may be unstable
What conditions must be met for mineralization to be initiated?
Homogenous nucleation
Heterogeneous mineralization
Removal, inactivation or exclusion of inhibitors
What is homogenous nucleation?
A local increase in the concentration of inorganic ions, allowing for ionic clusters to form
What is heterogeneous mineralization?
Nucleating substances lower the energy barrier and allow crystalites to form without increasing the local concentrations
What are the two ways that bone can form?
Endochondral ossification
Intramembranous ossification
Which type of bone formation does not involve chondrocytes?
Intramembranous ossification
Why type of bone does endochondral ossification form?
Long bone
What type of bone does intramembranous ossification form?
Flat bone
What are the two mechanisms for the initiation of mineralization?
Matrix vesicle
Mineralization of collagen fibrils
The matrix vesicle mechanism for initiation of mineralization is found where?
Endochondral cartilage
Woven bone
Mantle dentin
The mineralization of collagen fibrils mechanism of mineralization is found where?
Lamellar bone
Circumpulpal dentin
What sustains crystal growth once it is initiated?
Supersaturated solutions
Proteolipids from oral bacteria may make a major contribution to the formation of what?
Dental calculus
What is the matrix vesicle?
Small, membrane bound structure that buds off a cell within first formed organic matrix
What does the matrix vesicle contain?
Alkaline phosphatase Inorganic pyrophosphatase ATPase Phospholipid Glycolipid Polysaccharide
The matrix vesicles may act as ___ ___ for crystal growth.
Nucleation sites
How are calcium-inorganic phosphate-phospholipid complexes formed?
Via heterogeneous nucleation
When the vesicle rupture, what do they provide?
Seeds for radial crystal growth to form calcospherules
70-80% of mineral in bone is located where?
Within the fibrils
What governs the process of collagen mineralization?
Non-collagenous proteins
As governors of collagen mineralization, how do they mediate the process?
Some act as nucleator
Others control crystal growth
In collagen mineralization, where does mineral first appear?
In gap zones at the ends of collagen molecules
The gap zones of collagen molecules are initially filled with proteoglycan and bound calcium. How is the proteoglycan removed?
Proteolytically removed
How is it thought that enamel mineralizes?
By crystal growth from the already mineralized dentin
What are the two ways for calcium to reach a mineralization front?
Diffusion between cells
Transport through cells
What type of junctions exist between cells in enamel formation?
Tight junctions
What acts as the phosphate delivery service?
Alkaline phosphatase
What does alkaline phosphatase do?
Hydrolyses phosphate esters with an alkaline pH optimum
What is a possible function of alkaline phosphatase?
*Destroy inhibitors of HAP crystal growth
Transport of Pi
Locally increases Pi levels
The autosomal recessive disease hypophosphatasia is due to what?
Mutations in TNSALP gene
Humans have 4 specific ALP isozymes. Three are tissue specific. What are they?
Intestine
Placenta
Germ cell
Where is the 4th ALP isozyme found?
Ubiquitous, but especially abundant in liver, bone and kidney
What is TNSALP?
Tissue-nonspecificl ALP
Where is TNSALP found?
It is the ubiquitous ALP isozyme
In what demographic is hypophosphataisa most commonly seen?
Inbred mennonite families of Manitoba
What is the major problem in hypophosphatasia?
Mineralization is defective causing:
Skeletal and/or dental issues
*premature loss of deciduous teeth
How many forms of hypophosphatasia are there?
At least 6
What is the major dental disease that comes from hypophosphatasia?
Odontohypophosphatasia - lack of cementum leading to:
Retarded dentinogenesis
Enlarged pulp chambers
Premature loss of teeth
What type of crystal formation is affected by hypophosphatasia?
Vesicle-associated crystal formation
What is the main effect of a loss of the TNSALP enzyme?
Cause increased levels of PPi that act as inhibitors of HAP crystal growth
