Biomineralization Flashcards

1
Q

What is the mineral that makes up most of mineralized tissues of body

A

hydroxy apetitie

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2
Q

What are the mineralized tissues

A
  1. enamel (99% mineral)
  2. dentin (70% mineral)
  3. cementum (40%)
  4. bone (70%)
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3
Q

What are the mineralized tissue components

A
  1. organic components (proteins and soft molecules)

2. Mineral phase

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4
Q

What are the organic components

A

provide scaffold and regulate process

  1. collagen (except enamel)
  2. non collagenous proteins
  3. proteoglycans
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5
Q

what is part of the mineral phase

A

calcium hydroxyapetite (HAP) crystallites

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6
Q

what are features of HAP

A
  1. Not a pure compound

2. apatite is based on structure, not composition

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7
Q

How many diff crystal sytems are there

A

7:

  1. cubic
  2. tetragonal
  3. orthorhombic
  4. hexagonal
  5. monoclinic
  6. triclinic
  7. trigonal
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8
Q

What is a unit cell?How many ind units are there

A

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

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9
Q

what is a crystal made up of

A

multiple repeats of a unit cell.

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10
Q

What are the 4 types of unit cell

A
  1. I: body centered
  2. F: face centered
  3. C: side centered
  4. P: primitive
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11
Q

what is a crystal lattice

A

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.

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12
Q

A HAP crystal forms ____shaped prisms and plate like crystals

A

hexagonal

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13
Q

space restrictions prevent two ___groups oriented to each other so they dont interfere with each ohter

A

OH

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14
Q

Mesenchymal hard tissues are much ____than enamel

A

smaller; it has greater SA and more oppertunities for other molecules to interact with crystals of bone and dentin bc of this.

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15
Q

What is around crystals?

A

hydration layer; a layer of water exists around each crystallite that contains molecules that substitute into crystal and restructure it

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16
Q

Biological apatites are ____apatites

A

substituted

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17
Q

What can calcium be substittued for

A
  1. Na
  2. Mg
  3. Pb, Zn, Cu
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18
Q

What can PO4 be substituted for

A

carbonate

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19
Q

What can OH be substituted for

A

F, Cl, CO3

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20
Q

Apatites of normal bone, enamel, and dentin are principally:

A

type B carbonate apatites

  • B type: carbonate for phosphate
  • A type: carbonate for hydroxyl
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21
Q

Carbonate makes the crystals ____ and flouride make the crystals

A

weaker; stronger

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22
Q

Explain effect of carbonate substituion on the mineral phase

A
  1. Changes dimension of crystal
  2. increases its solubility
  3. more susceptible to acid dissolution
  4. favors caries.
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23
Q

___contains the least amount of carbonate, Mg, and Na. ___ and dentin contain the most

A

Enamel; bone

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24
Q

What is the effect of flouride substitution on the mineral phase

A
  • 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
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25
Q

How is HAP formed in the body

A

By intermediate steps

  1. Calcium and phosphorus form brushite
  2. Brushite forms whitlockite
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26
Q

which intermediate is the most stable form

A

HAP

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27
Q

How many grams of calcium in body

A

1000g; 12 g outside of bone; 1-1.5 in body fluids

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28
Q

What is needed for absorption of calcium

A

Vitamin D

29
Q

What is the amount of phosphate in body

A

700g; 100g outside of bone; 50 g in muscle

30
Q

What are sources of Calcium and phosphate for mineralizaiton

A

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.

31
Q

There is a ____fold diff between Ca inside of cell than Ca outside of cell

A

1000

32
Q

_____ is the main source of Ca and P for remineralization of enamel

A

Saliva

33
Q

Calcium and phosphate levels in biological fluids are _____controlled

A

homeostatically

34
Q

How does parathyroid hormone function

A

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.

35
Q

How does calcitonin function

A

Promotes bone formation. Activates osteoblasts to put calcium back onto the bone.

36
Q

What do Vitamin D metabolites do

A

Absorption of calcium from the GI tract.

37
Q

If intracellular calcium concentration is higher than 10^-6 :

A

you get apoptosis

38
Q

What is the amount of calcium extracellularly

A

10^-3

39
Q

____ and ___ are supersaturated with respect to HAP

A

Serum and saliva; If there were no inhibitors, the crystals would continue to grow, but there ARE inhibitors in saliva.

40
Q

What are the salivary inhibitors

A
  1. Statherin
  2. aPRPs (acidic proline rich proteins)
  3. PPi (pyrophosphates)
    - In order to remineralize teeth you have to get rid of these.
41
Q

When is saliva supersaturated

A

7.4

42
Q

At what pH will enamel dissolve

A

below 5.2; white spots lead to caries

43
Q

What is the mechanism of crystallization

A

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.

44
Q

What is regulated in order for mineralization to occur

A
  1. the initiation and amount of mineralization
  2. the crystal size
  3. the shape
45
Q

What conditions must be met in order for mineralization to be initiated

A
  1. Homogenous nucleation: a local increase in the conc of inorganic ions allows a suff. number of ionic clusters to form.
  2. Heterogenous mineralization:nucleating sub’s lower the energy barrier and allow crystallites to form w/o inc. the local conc.’s.
  3. Removal, inactivation or exclusion of inhibitors.
46
Q

What are two ways bones are formed

A
  1. Endochondral ossification

2. Intramembranous ossification

47
Q

What is endochondral ossification

A
  1. Start off with cartilage; chondryctes –> osteoblasts; guide the mineralization of the cartilage: allow formation of long bones
48
Q

What is intramembranous ossification

A

NO cartilage involved. Ostebolasts produce osteoid which is type 1 collagen: form flat bones; ex: scapula, sternum, ribs, patella

49
Q

What are two mechanisms of initiation

A
  1. matrix vesicle

2. mineralization of collagen fibrils

50
Q

What is the mechanism of matrix vesicle predominant in

A
  1. endochondral cartilage
  2. woven bone
  3. mantle dentin
51
Q

what is the mechanism of mineralization of collagen fibrils predominant in

A
  1. lamellar bone

2. circumpulpal dentin

52
Q

What is involved in both mechanisms of crystal growth

A

phopholipids; find CaPi phopsholipid complexes in calcified tissue and proteolipids from oral bacteria make contribution to formation of dental calculus.

53
Q

Explain how matrix vesicles function in mineralization

A

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.

54
Q

The inorganic part of bone matrix is

A

HAP

55
Q

What are the organic components of bone matrix

A

88% type 1 collagen and the rest are regulators; they either inhibit or promote bone formation

56
Q

What is the process of colalgen mineralization

A

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.

57
Q

In bone, ____% of mineral is loc within the fibrils

A

70-80%

58
Q

T/F Collagen itself likely has no role in initiation

A

True

59
Q

Process of collagen mineralization is governed by ___ ____ proteins

A

non collagenous proteins; they’re also thought to influence the size and shape of crystals that form

60
Q

Compare and contrast how dentin is mineralized vs bone

A

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.

61
Q

State the principle diff’s bet enamel and other mineralized tissues

A

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).

62
Q

List known matrix proteins implicated in the control of matrix mineralization, and their postulated functions.

A

osteopontin, ostenectin, BSP II, dentin sialoprotein,

63
Q

How does calcium get to mineralization front?

A
  1. transport through cells

2. diffusion between cells

64
Q

How does phosphate get to mineralization front

A

Alkaline phosphatase

65
Q

Describe the general properties of ALP, and list potential functions in mineralization

A
  1. Locally inc Pi levels
  2. Destroys inhibitors of HAP crystal growth
  3. Transport of Pi
  4. Ca++ binding protein
  5. Ca/Mg ATPase
  6. Tyrosine specific phosphoprotein phosphatase
66
Q

Explain the molecular basis of hypophosphatasia

A

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
67
Q

What is odontohypophosphatasia

A
  • Dental disease
  • incisors most affected
  • premature loss of teeth due to lack of cementum
  • enamel is ok
68
Q

What does hypophosphatasia affect

A

vesicle associated crystal formation

-main effect of loss of enzyme may be due to cause of increased levels of PPi.