What is the mineral that makes up most of mineralized tissues of body
What are the mineralized tissues
- enamel (99% mineral)
- dentin (70% mineral)
- cementum (40%)
- bone (70%)
What are the mineralized tissue components
- organic components (proteins and soft molecules)
2. Mineral phase
What are the organic components
provide scaffold and regulate process
- collagen (except enamel)
- non collagenous proteins
what is part of the mineral phase
calcium hydroxyapetite (HAP) crystallites
what are features of HAP
- Not a pure compound
2. apatite is based on structure, not composition
How many diff crystal sytems are there
What is a unit cell?How many ind units are there
a conceptual entity rep. the smallest section of a crystal that reps the structure of the solid as a whole. There are 4 types of units
what is a crystal made up of
multiple repeats of a unit cell.
What are the 4 types of unit cell
- I: body centered
- F: face centered
- C: side centered
- P: primitive
what is a crystal lattice
crystals are made of identical unit cells stacked in some ordered fashion. The infinite array of identical points is the crystal lattice.
-The pattern of repetition of the unit cell.
A HAP crystal forms ____shaped prisms and plate like crystals
space restrictions prevent two ___groups oriented to each other so they dont interfere with each ohter
Mesenchymal hard tissues are much ____than enamel
smaller; it has greater SA and more oppertunities for other molecules to interact with crystals of bone and dentin bc of this.
What is around crystals?
hydration layer; a layer of water exists around each crystallite that contains molecules that substitute into crystal and restructure it
Biological apatites are ____apatites
What can calcium be substittued for
- Pb, Zn, Cu
What can PO4 be substituted for
What can OH be substituted for
F, Cl, CO3
Apatites of normal bone, enamel, and dentin are principally:
type B carbonate apatites
- B type: carbonate for phosphate
- A type: carbonate for hydroxyl
Carbonate makes the crystals ____ and flouride make the crystals
Explain effect of carbonate substituion on the mineral phase
- Changes dimension of crystal
- increases its solubility
- more susceptible to acid dissolution
- favors caries.
___contains the least amount of carbonate, Mg, and Na. ___ and dentin contain the most
What is the effect of flouride substitution on the mineral phase
- Substitutes for OH in unit cell:
1. makes crystals larger; more tightly packed
2. Dec’s solubility
3. Promotes repair of caries lesions by remineralization
4. Promotes formation of F-HAP
5. Minimizes incorporation of HPO4
6. minimized negative effects of other ions
How is HAP formed in the body
By intermediate steps
- Calcium and phosphorus form brushite
- Brushite forms whitlockite
which intermediate is the most stable form
How many grams of calcium in body
1000g; 12 g outside of bone; 1-1.5 in body fluids
What is needed for absorption of calcium
What is the amount of phosphate in body
700g; 100g outside of bone; 50 g in muscle
What are sources of Calcium and phosphate for mineralizaiton
Free ions in body fluids. Serum is the main source of Ca and P for bone. Ca in body has to be tightly reg. Important for brain and muscle function.
There is a ____fold diff between Ca inside of cell than Ca outside of cell
_____ is the main source of Ca and P for remineralization of enamel
Calcium and phosphate levels in biological fluids are _____controlled
How does parathyroid hormone function
Stimulates cells on surface of bone and Acts to release Calcium to keep levels high. It activates osteoclasts and directly resorb bone and put it back into serum and also work on kidney to reabsorb calcium.
How does calcitonin function
Promotes bone formation. Activates osteoblasts to put calcium back onto the bone.
What do Vitamin D metabolites do
Absorption of calcium from the GI tract.
If intracellular calcium concentration is higher than 10^-6 :
you get apoptosis
What is the amount of calcium extracellularly
____ and ___ are supersaturated with respect to HAP
Serum and saliva; If there were no inhibitors, the crystals would continue to grow, but there ARE inhibitors in saliva.
What are the salivary inhibitors
- aPRPs (acidic proline rich proteins)
- PPi (pyrophosphates)
- In order to remineralize teeth you have to get rid of these.
When is saliva supersaturated
At what pH will enamel dissolve
below 5.2; white spots lead to caries
What is the mechanism of crystallization
formation of a cluster of ions requires energy; so an energy barrier must be overcome for crystallization to occur; Inhibitors of crystal formation are present that raise the energy barrier.
What is regulated in order for mineralization to occur
- the initiation and amount of mineralization
- the crystal size
- the shape
What conditions must be met in order for mineralization to be initiated
- Homogenous nucleation: a local increase in the conc of inorganic ions allows a suff. number of ionic clusters to form.
- Heterogenous mineralization:nucleating sub’s lower the energy barrier and allow crystallites to form w/o inc. the local conc.’s.
- Removal, inactivation or exclusion of inhibitors.
What are two ways bones are formed
- Endochondral ossification
2. Intramembranous ossification
What is endochondral ossification
- Start off with cartilage; chondryctes –> osteoblasts; guide the mineralization of the cartilage: allow formation of long bones
What is intramembranous ossification
NO cartilage involved. Ostebolasts produce osteoid which is type 1 collagen: form flat bones; ex: scapula, sternum, ribs, patella
What are two mechanisms of initiation
- matrix vesicle
2. mineralization of collagen fibrils
What is the mechanism of matrix vesicle predominant in
- endochondral cartilage
- woven bone
- mantle dentin
what is the mechanism of mineralization of collagen fibrils predominant in
- lamellar bone
2. circumpulpal dentin
What is involved in both mechanisms of crystal growth
phopholipids; find CaPi phopsholipid complexes in calcified tissue and proteolipids from oral bacteria make contribution to formation of dental calculus.
Explain how matrix vesicles function in mineralization
ACt as nucleation sites for crystal growth; calcium inorganic phosphate phospholipid complexes form inside, you then get heterogenous nucleation. Vesicles then rupture and provide seeds for radial crytal growth to form calcospherules.
The inorganic part of bone matrix is
What are the organic components of bone matrix
88% type 1 collagen and the rest are regulators; they either inhibit or promote bone formation
What is the process of colalgen mineralization
Mineral forms within the collagen; HAP molecules become seated once the inhibitors are removed from the spaces. Molecules form firbrils and become mineralized bet the end. Fibrils make fibers which make patterns called osteons.
In bone, ____% of mineral is loc within the fibrils
T/F Collagen itself likely has no role in initiation
Process of collagen mineralization is governed by ___ ____ proteins
non collagenous proteins; they’re also thought to influence the size and shape of crystals that form
Compare and contrast how dentin is mineralized vs bone
Dentin: Odontoblasts have long projections; when teeth are being formed, these form collagen fibrils on which mineralization occurs. Odontoblasts sends projection from inside to outside of tooth which creates canals, this allows inside of tooth to be sensitive in changes of pressure, etc.
Bone: osteoclast removes surface; it gets refilled in; osteblast lays down matrix and fills in holes. Collagen molecules mineralize and form bone.
State the principle diff’s bet enamel and other mineralized tissues
Enamel doesnt involve collagen at all! Enamel grows by already mineralized dentin. Size and shape of crystals det by enamel matrix proteins (amelogenin, enamelin, etc).
List known matrix proteins implicated in the control of matrix mineralization, and their postulated functions.
osteopontin, ostenectin, BSP II, dentin sialoprotein,
How does calcium get to mineralization front?
- transport through cells
2. diffusion between cells
How does phosphate get to mineralization front
Describe the general properties of ALP, and list potential functions in mineralization
- Locally inc Pi levels
- Destroys inhibitors of HAP crystal growth
- Transport of Pi
- Ca++ binding protein
- Ca/Mg ATPase
- Tyrosine specific phosphoprotein phosphatase
Explain the molecular basis of hypophosphatasia
Tissue non specific ALP isozyme is in liver, bone and kidney. An autosomal recessive disease, hypophosphatasia can happen due to mutations in TNSALP gene:
- Serum calcium and Pi levels are normal
- Mineralization defective: skeleton/dentition can be affected. Premature loss of deciduous teeth, a major clinical feature.
- In fetus can cause death
What is odontohypophosphatasia
- Dental disease
- incisors most affected
- premature loss of teeth due to lack of cementum
- enamel is ok
What does hypophosphatasia affect
vesicle associated crystal formation
-main effect of loss of enzyme may be due to cause of increased levels of PPi.