THEORIES OF
MINERALIZATION
Objectives Medium Assessment Time( mins)
Introduction Power point Theory based 10 min
Process of assessment using short
mineralization answer
Theories of Power point Theory based 15 min
mineralization assessment using short
essay
Inhibitors of Power point Theory based 15 min
Mineralization assessment using short
essay
Enamel Mineralization Power point Theory based 1 min
assessment using short
essay
Conclusion Lecture using Power 5
Point
Recap Lecture using Power 5
Point
EXPLAIN MECHANISM OF HARD TISSUE
FORMATION
STUDY OF VARIOUS THEORIES
PROPOSED
UNDERSTANDING OF DIFFERENCES IN
MINERALIZATION OF THE DENTAL HARD
TISSUES
What is mineralization?
Physiologic
deposition of minerals.
Minerals are insoluble Ca salts in organic
matrix
calcium phosphate in bone and teeth.
Part of hard tissue formation
Bone, cementum and dentin
- specialized connective tissue
- collagen - determine structure
Genesis of hard tissue
formed by
1. Formation of organic matrix
2. Calcification of formed matrix
Formation of organic matrix
formative blast cells
contain rER, golgi apparatus and secretory
granules
Formation of Organic
matrix:
Specialized cells- Osteoblasts—bone
Odontoblasts– dentine
Cementoblasts– cementum
Osteoid: Collagen (type 1)
Ground substance ( acidic
mucopolysaccarides)
Non collagenous subs: inhibitor\inducer of min.
Wat are minerals?
Inorg portion of hard tissue contains
Ca hydroxy apatite crystals
Hexagonal in shape
Stacked together to form a lattice
Repetition of this arrangement produce
crystals of various sizes[ needle like
/ plate like]
Mechanism of Mineralization
precipitation, formation and growth of
hydroxyapatite crystals
Involves inhibitory mechanisms that can
counterbalance or inhibit these processes
incompletely understood till date
Most difficult step to explain is the formation of
the first crystals.
Mineralisation or calcification is defined
as the deposition of inorganic
substance mainly calcium on the
organic portion of a hard tissue.
Mechanisms:
Mechanisms that would locally rise the calcium and
phosphate solution ion product to levels at which
mineral would precipitate spontaneously
HOMOGENOUS NUCLEATION
Mechanisms or substances that would create nucleating
sites or remove barriers to these sites
HETEROGENEOUS NUCLEATION
Mechanisms or substances that prevent mineral
formation- remove or render inactive to permit
calcification.
THEORIES PROPOSED
BOOSTER THEORY (phosphatase theory)
Alkaline phosphatase theory
(Accepted till 1950)
SEEDING OR NUCLEATING OR EPITAXIC
THEORY (1950-1960)
MATRIX VESICLES THEORY (After 1960)
BOOSTER MECHANISM(PHOSPHATASE T)
Alkaline Phosphatase theory: Robinson
Alkaline phosphatase operating at high ph is
capable of hydrolyzing organic phosphate esters with
the release of inorganic phosphate ions. So it probably
increases the local concentration of inorganic
phosphate ions and cause the precipitation of calcium
phosphate, when its solubility product is exceeded.
Studied on rachitic animals
Calcifiable organic matrix contains alk
phosphatase
hydrolyses
Org phosphatase
Releases inorg ortho phosphatase
increase in PO4 ion conc
Boosting effect causes spontaneous
precipitation
Po4 ions reacts with Ca ions present in
tissue fluids
releases
Amorphous Ca2 Po4 which is unstable
Forms stable Ca hydoxyapatite crystals
Failure of theory:
1. Alkaline Phosphatase was found to present in
tissues which did not normally calcify.
2. Concentration of organic phosphate in plasma
was too low for this to serve as an effective
source of phosphate ions.
3. Certain enzyme inhibitors which did not affect
phosphatase were found to inhibit calcification
Role of alkaline phosphate
Helps in ion transport
Helps in removing crystal poisons
Forms inorganic phosphates which help
in mineralisation
SEEDING OR NUCLEATING THEORY
(Neuman and Neuman(1958))
prerequisite like nucleating substances are necessary
Nucleating substance:
collagenous Noncollagenous
-Glycosoaminoglycans
-Proteoglycans
-Gamma carboxyGA
-Phosphoproteins
NATURE OF SEEDING: The molecules might have a
distribution of electric charges or a spatial configuration
such that calcium and phosphate ions become attached to
adjacent regions.
Collagen as a seed
Nucleation occurs on collagen with 64nm banding with presence of 6A
hole zones in the non overlap region of the collagen fibril. Minerals first
appear in the gap zones at the end of collagen molecules
Aminoacid serine present in collagen might attract calcium ions and act
as nucleating centre
Proteoglycans present in the hole zones bind to calcium. Later
phosphoproteins bind to collagen.
Dephosporylation of the phosphoproteins (by alkaline phosphatase)
provides the additional phosphate ions for nucleation and crystal growth.
Other seeding agents
Lipids: Triglycerides, free fatty acids &
various phospholipids which contain
serine attract calcium.
Phosphoproteins, in which a phosphate
group is attached to serine may also act
as seeds (dentine)
Only the collagen of bone acts
as seed but not of skin or
tendon. ???
Spaces b/n collagen molecules in bone and dentine
averages 6A which is larger than in tendon.
Other tissues contain specific nucleation inhibiting
molecules in their collagen. Like polyphosphates
( ATP, pyrophosphate and tripolyphosphate)
DRAWBACKS
Unable to explain mineralisation of all
Tissues
Enamel has no collagen but 96%
mineralised
Mineralisation of cartilage begins in ground
subs nth to do with collagen
Mitochondria proposed to a nucleation
zone
MATRIX VESICLES THEORY
Small round membrane bound structure that buds off
from the cell to form an independent unit within the
first formed organic matrix.
These vesicles contain
Alkaline phosphatase, Convert pyrophosphate into
Pyrophosphatase, orthophosphate thus removing the
inhibitory power(Homo-nuc)
Phospholipids
Proteoglycans, Attract calcium to form calcium
inorganic phosphate phospholipid
calcium ATPase, complex.(Hetero nuc)
Mettalloproteinases,
Types of vesicles
Type 1 Type 2
Round or ovoid Irregular membrane
Aryl phosphatase bound structures
Acid phosphatase Alk phosphatase
They break down Pyrophosphatase
pyrophosphatase Phospholipids
(proteoglycans, Annexin v
GAG)which are inhibitors
metalloproteinase
of mineralisation
Function of alk phosphatase enzyme
It hydrolyses organic phosphate ions
from organic matrix at an alkaline pH
and thereby increases the inorganic
phosphate concentration
When associated with cell membranes
- role in ion transport
Function of pyrophosphatase :
Cleaving pyrophosphate
- permitting crystal growth
Annexin V :
Membrane associated protein
It:
- regulates influx of ca2+ ions into
matrix vesicle
- binds the matrix vesicle to collagen
fibers in the organic matrix
Provides a microenvironment in which all
the proposed mechanisms for initial
mineralization exists
Alk phosphatase breaks down Phosphate
esters to form inorganic phosphates which
enters the vesicle
phopholipids
ca Ca-inorganic P04
+ = Phospholipid
complex
Lipids – initial mineralization
HA crystal formation occurs within the
vesicle
More ions are added – crystal growth
continues
Rupture of vesicle membrane
In the matrix they absorb more ions from
fluid
Initially calcospheric mass formed –
fuses to form a uniform mineralised
matrix
Difference in Mineralization of
dental hard tissues
ENAMELOGENESIS
No matrix vesicles - enamel protein.
Enamel proteins is deposited into mineralized
dentin
enamel mineralization is thought to be achieved by
crystal growth from the already mineralized dentin.
DENTINOGENESIS
MANTLE DENTIN FORMATION
Matrix vesicles
Phosphoryn & phospholipids are absent
PRIMARY CIRCUMPULPAL DENTIN
matrix vesicles - not formed
heterogenous nucleation
Lipids, phosphoproteins, phospholipids &
gamma carboxyglutamate proteins
Globular calcification: Calcospherules, are initiated in
separate isolated foci. Large globular masses arise &
coalesce.
CEMENTOGENESIS
No matrix vesicle formation
Presence of neighbouring hydroxyapatite in
dentine initiates mineralization.
No calcospherite formation.
Thank you
