functional matrix theory and articles by melvin moss

2. AMERICAN JOURNAL OF ORTHODONTICS ,1969

3. Function In Head
Functional Matrix Component
Functional Matrix Skeletal Unit
Growth change is secondary

4. SKELETAL UNIT
BONE, CARTILAGE OR TENDINOUS ≠ “BONES” OF CLASSICAL
TISSUE OSTEOLOGY
Such a “Bone” No. of a skeletal unit
MICRO SKELETAL UNIT
No. of neighboring
“bones”
As a single cranial component
MACRO SKELETAL
UNIT

5. Micro skeleton unit of mandible
Coronoid micro skeletal unit temporalis muscle
Angular micro skeletal unit masseter and
medial pterygoid muscles
Alveolar micro skeletal unit presence and
position of teeth
Basal micro skeletal unit inferior alveolar
neuro vascular triad
Each micro skeleton unit is independent of each other

6. FUNCTIONAL MATRIX
(muscle, glands, nerves, vessels, fat)
PERIOSTEAL MATRIX CAPSULAR
MATRIX MATRIX
Muscles, blood vessels, functioning space or organ
Nerves, glands and teeth
Produces Morphological cause expansion
Changes In their skeletal
Unit
deposition and translation as a whole
resorption of bone tissue

7. • There exists confirmatory data which shows that
experimental removal of the mammalian temporalis muscle
or its denervation results in actual diminution of coronoid
process size and shape or it’s total disappearance
PERIOSTEAL MATRIX

8. • Finally, it is ,established also that experimental or clinical
alteration of the muscles attaching to the other mandibular
ramal skeletal units can produce compensatory changes in
temporalis muscle function. This will equally well change the
size and shape of the coronoid process in proportion to the
degree of muscular imbalance produced.
Hypertrophy/ hyperactivity Increased Coronoid
Of Temporalis size and shape

9. • It is believed that the changes in size and/or shape
brought about by deposition and resorption of bone tissue
constitute the entire phenomenon of growth, then one is
forced to the logical conclusion that the change in
horizontal position of the mandibular ramus during growth
is produced entirely as a result of such direct
microskeletal unit tissue responses to periosteal matrices,
be these tissues osseous or cartilaginous.

10. CAPSULAR MATRICES
• All skeletal units, and thus all bones in the formal sense,
arise, exist, grow, are maintained, and respond
morphologically while totally embedded within their functional
periosteal matrices.
• At the same time, all these functional cranial components
(functional matrices plus skeletal units) are organized in the
form of cranial capsules.

11. • Capsular matrix are of 2 types -
1) neurocranial capsule 2) orofacial capsule
• Each of these capsules is an envelope which contains a
series of functional cranial components (skeletal units plus
their related functional matrices)are sandwiched in between
two covering layers.
• In the neurocranial capsule these covers consist of the skin
and the dura mater, whereas in the orofacial capsule the skin
and mucosa form these limiting layers.
• All spaces intervening between functional components
themselves, and between them and the limits of the capsule,
are filled with indifferent loose connective tissue.

12. • Each capsule surrounds and protects a capsular functional
matrix

13. Neurocranial matrices
• In the neurocranium, we are dealing with volume of neural
mass.
• The expansion of this enclosed and protected capsular
matrix volume is the primary event in the expansion of the
neurocranial capsule.
• The response of the capsule, is to expand in a
compensatory manner.

14. • All of the included and enclosed functional cranial
components, that is, the periosteal matrices and their
microskeletal units, are then obligatorily carried outward
within the capsule in a totally passive manner.
• The calvarial functional cranial components,are passively
and secondarily translated in space without need of
deposition and resorption and activity of periosteal matrices
on their respective microskeletal units goes on
simultaneously.

15. • When we examine these pathologic, or experimentally
produced, situations in which periosteal matrices have
been prevented from exerting their morphogenetic activity,
we can observe clearly the passive, nonperiosteal,
translative growth produced by the capsular matrices.
• To conclude neurocranial capsule, the expansion of the
neural mass is the primary event which causes the
secondary and compensatory growth of the neural skull.

17. OROFACIAL MATRICES
• All functional cranial components of the facial skull
arise, grow, and are maintained within an orofacial
capsule
• This capsule surrounds and protects the oro-naso-
pharyngeal functioning spaces.
• The volumetric growth of these spaces which is the
primary morphogenetic event in facial skull growth.

18. • The oral and pharyngeal region are said to have primary
function in maintaining a patent airway.
• This is accomplished by a dynamic musculoskeletal
postural balance which is termed the “airway-maintenance
mechanism. ”

19. The bilateral removal of mandibular condylar cartilages, does
not inhibit either the translation of the acondylar complex of
mandibular functional cranial components; nor does it inhibit
the changes in the form of their microskeletal units as their
individual matrices alter their functional demands.

20. MANDIBULAR GROWTH
• Mandibular growth is seen now to be a combination of the
morphologic effects of both capsular and periosteal matrices.
• The capsular matrix growth causes an expansion of the
capsule as a whole.
• The enclosed and embedded macroskeletal unit
accordingly, is passively and secondarily translated in space
to successively new positions.

21. • In normal conditions the periosteal matrices related to the
constituent mandibular microskeletal units also respond to
this volumetric expansion.
• Such an alteration in their position causes them to grow; that
is, causes changes in their functional demands.
• These now call direct alterations in the size and shape of
their microskeletal units.
• The sum of translation plus changes in form comprises the
totality of mandibular growth.

22. Conclusion
• The origin, growth and maintenance of all skeletal tissues and
organs are always secondary compensatory and obligatory
responses to temporally and operationally prior events or
processes that occur in specifically related nonskeletal tissues,
organs or functioning spaces (functional matrices).
• Two basic types of such matrices-periosteal and capsular
• Periosteal matrices include muscles and teeth, and they act
upon skeletal units by osseous deposition and resorption
• There net affect is to alter the form(size and shape) of their
respective skeletal units.

23. • The capsular matrices arc conceived of as volumes enclosed
and protected by both the neurocranial(neural mass) and the
orofacial capsules.
• Capsular matrices act upon functional cranial components as a
whole in a secondary and indirect manner. They do so by
altering the volume of the capsules within which the functional
cranial components are embedded and they cause translation of
cranial part.
• Cranial growth is a combination of the morphogenetically
primary activity of both types of matrix. Growth is
accomplished by both translation and changes in form.

24. AMERICAN JOURNAL OF ORTHODONTICS ,1997

25. Constraints of FMH
• 1. Methodological: FMH used only macroscopic measurement
by using point mechanics and arbitrary reference frames like
roentgenographic cephalometric radiographs permitting only
method-specific descriptions that can not be structurally
detailed.
• This constraint was overcome by using continuum mechanics
techniques of the finite element method and of the related
macro and boundary element methods.
• This method added quantitative aspects of localized cephalic
growth kinematics to the earlier qualitative description of growth
dynamics.

26. Hierarchical Constraint
• FMH does not explain how extrinsic , epigenetic functional
matrix stimuli are transduced into regulatory signals at the
cellular, and molecular levels..
• The epigenetic could not explain or predict the higher attribute
of the bone tissue.
• The new version of FMH tries to bridge the gap between
hierarchical constraints and explains the operation from genome
to organ level by two concepts:
1. Mechanotransduction occurring in single cells.
2. That bone cells function multicellularly as a connected
cellular network.

27. MECHANOTRANSDUCTION
• MECHANO: : relating to a mechanical source;
mechanical
• TRANSDUCTION : any process by which a biological
cell converts one kind of signal or stimulus into
another.

29. Osseous Mechanotransduction
• Static and dynamic loadings are continuously applied to
bone tissues tending to deform both extracellular matrix
and bone cells.
• When appropriate stimulus exceeds threshold values
• Loaded tissue responds by bone cell adaptation
processes
• Osteocytes and osteoblasts are competent for
intracellular stimulus reception and transduction and
subsequent signal transmission.

30. • The osseous mechanotransduction has four unique properties:
1. Bone cells are not cytologically specialized like other
mechanosensory cells.
2. Single bone loading stimulus evokes three adaptational
responses, whereas the non osseous process generally evokes
one.
3. Osseous signal transmission is aneural; it does not involve
neural pathways, unlike other mechanosensory signals.
4. The adaptational response is confined within the individual
bone organ independently.

31. Mechanotrasnductive
processes
1. IONIC: brings about the transport of ions through the osteocytic
plasma membrane resulting in the creation of an electrical signal.
Stretch activated channels
• Loading S-A get activated
Electrical processes:- These include several
mechanotransductive processes:-
• Electromechanical, Electrokinetic and Electric field strength.
Intracellular electric events
passage of certain ion K+, Ca+
and Na+

32. 1) ELECTROMECHANICAL:- Voltage-activated ion channels in
the osteocytic plasma membrane hint at a mechanism for
transmembrane ion flow, crucial for mechanotransduction.
These flows might also trigger osteocytic action potentials
transmitted through gap junctions.
2) ELECTROKINETIC:- Bone tissue contains electric charges
in its fluid, termed electrokinetic, generating streaming
potential (SP) rather than piezoelectricity. SP measures
strain-generated potential (SGP) from charge convection in
deformed bone fluid flow. An SPG of +2 mV typically
stimulates osteogenesis and osteocytic action potentials.

33. 3) ELECTRIC FIELD STRENGTH:- Bone responds to
external electrical fields, possibly influenced by field
strength, which correlates with muscle activity. Effective
field strengths range from 1 to 10 μV/cm, resembling
those during normal muscle activity.

34. 2. Mechanical process:-
• The basis of this mechanism is the physical continuity of the
transmembrane molecule integrin.
• This molecule is connected extracellularly with the
macromolecular collagen of the organic matrix and intracellularly
with cytoskeletal actin.
• It is suggested that such a cytoskeletal lever chain can provide a
physical stimulus able to activate the osteocytic genome.

35. 1997 American Journal Of Orthodontics and
Dentofacial Orthopedics
Aim:- To Consider The Implications Of The FMH And The
Inclusion Of Connectionist Network Theory

36. BONE AS AN OSSEOUS CONNECTED
CELLULAR NETWORK (CCN)
All bones cells (except osteoclasts)
are extensively interconnected by
gap junction and form an osseous
connective cellular network.
Osteocytes have cytoplasmic
processes which are oriented three
dimensionally and are
architecturally well-suited to sense
deformation of the mineralized
matrix.

37. GAP JUNCTION- are found where plasma membrane of
pair of markedly overlapping cannicular process meet.
Gap junctions connects:-
• Superficial osteocytes to periosteal and endosteal osteoblast
• Periosteal osteoblast with pre-osteoblastic cells and these in
turn are similarly interconnected.

38. • Gap junctions are electrical synapses, in
contrast to interneuronal, chemical
synapses. They permit bidirectional signal
traffic, e.g., Biochemical, ionic.
• Mechanotransductively activated bone
cells, e.g., Osteocytes, can initiate
membrane action potentials capable of
transmission through interconnecting gap
junctions.

39. • CCN is operationally analogous to an
"artificial neural network, in which
massively parallel or parallel-
distributed signal processing occurs.
• In network theory, these cells are
organized into "layers": an initial
input, a final output, and one or
more intermediate or "hidden"
layers.

40. Initial cell layers- Osteocytes (mechanoreceptors) sense stimuli
from periosteal functional matrix
Summation of all the inputs
Comparison & intercellular mechanotransduction
hidden cell layers-
(i.e. Adj. Osteocytes)propagation of action potential
Final cell layer(osteoblasts) output

41. NETWORK THOERY
• Information is not stored discretely in a CCN, as it is in a
conventional, single CPU computer. Rather it is distributed
across all or part of the network, and several types of information
may be stored simultaneously.
• The instantaneous state of a ccn is a property of the state of all
its cells and of all their connections. Accordingly, the
informational representation of CCN is redundant, assuring that
the network is fault or error tolerant, i.E., One or several
inoperative cells causes little or no noticeable loss in
network operations, which is a matter of useful clinical
significance.

42. • The ccns show oscillation, i.E., Reciprocal signaling
(feedback) between layers. This attribute enables them to
adjustively self-organize
• This behavior is related to the fact that biologic ccns are
not preprogrammed; rather they learn by unsupervised or
epigenetic “training”.
• Gap junctions are electrical synapses that permit
bidirectional flow of information, are the cytological basis
for the oscillatory behavior of a ccn.

43. ATTRIBUTES OF CCN
• Developmentally, it is an untrained self-organized, self-adapting
and epigenetically regulated system.
• Operationally, it is a stable, dynamic system that exhibits
oscillatory behavior permitting feedback.
• Structurally, an osseous CCN is nonmodular, i.e., the variations
in its organization permit discrete processing of differential
signals.
• It is this attribute that permits the triad of histologic responses to
a unitary loading event.

44. • Strain probably plays the primary role and is a competent
stimulus in bone remodeling responses.
• The significant strain attribute may vary with specific conditions.
These include:-
1. Loading category- Bone responds best to dynamic rather
static loading.
2. Frequency- Osteocytes may be physiologically "tuned" to the
frequencies of muscle function. High order frequencies,
significantly related to bone adaptational responses.
3. Magnitude- Relatively small microstrains are
morphogenetically competent.

45. CONCLUSION
• Where the original FMH version offered only verbal
descriptions of periosteal matrix function and skeletal unit
response, the addition to the FMH of the concepts of
mechanotransduction and of computational bone biology
offers an explanatory chain extending from the epigenetic
event of skeletal muscle contraction, hierarchically
downward, through the cellular and molecular levels to
the bone cell genome, and then upward again, through
histologic levels to the event of gross bone form
adaptational changes.

46. AJODO,1997

47. •The initial version of the functional matrix hypothesis
(FMH), claiming epigenetic control of morphogenesis,
was based on macroscopic experimental, comparative,
and clinical data.
• Recently revised, it now extends hierarchically from
gross to microscopic levels and identifies some
epigenetic mechanisms capable of regulating genomic
expression.

48. ODONTOGENIC EXAMPLE OF
GENOMIC/EPIGENETIC DICHOTOMY

49. • Because each dental replacement cycle involves
identical odontogenic stages, it is postulated that:
(1) Mechanical forces, related to differential diet
"hardness," generate epigenetic signals,
mechanotransductively processed by dental papilla
cells; and
(2) These signals control at least the temporal and
spatial expression of genomic products related to the
development of differential tooth form, such as size
and shape.

50. THE GENOMIC THESIS
• The genomic thesis holds that the genome, from the
moment of fertilization, contains all the information
necessary to regulate (cause, control, direct)
(1) The intranuclear formation and transcription of mrna
and
(2) all of the intracellular and intercellular processes of
subsequent, and structurally more complex, cell,
tissue, organ, and organismal morphogenesis

51. • Therefore, morphogenesis is but the predetermined
reading-out of an intrinsic and inherited genomic
organismal blueprint
• For example, specific patterns of gene regulation cause,
control, regulate, determine the mechanisms by which a
fertilized egg divides and progresses through the various
decision points to yield groups of cells that are first
determined to become and then actually differentiate to
become specialized tissues of the right dimension and in
the proper location

52. • Molecular (gene) genetics extended the claims of the
thesis to the regulation of all aspects of ontogeny (i.E.,
Of "growth and development").
• The mega-human genome project, explicitly intends to:
1. Describe the complete human genome;
2. Demonstrate genomic controls of all
developmental processes, at all structural levels,
from the subcellular to the organismal;
3. In a societal context, possibly lead to some type
of neoeugenics.

53. BIOLOGIC BASES FOR GENOMIC
THESIS
• The somatic cells of an individual metazoan inherit two classes
of molecular information:
1. An identical diploid DNA and
2. The maternal cytoplasmic constituents of the egg: e.g.,
Mitochondria, cytoskeleton, membranes.
• Only approximately 10% of the genome seems related to
phenotypic ontogenesis, whereas, well over 90% does not
encode precursors to mrnas or any other rna.

55. THE GENOMIC THESIS IN ORAFOCIAL BIOLOGY
• There is extensive support for the genomic thesis in the
orofacial biology literature, with most genetic studies of
cephalic or cranial morphogenesis explicitly or implicitly
assuming genomic regulation of each anatomical structure.
• Prenatal craniofacial development is controlled by two
interrelated, temporally sequential, processes:
(1) initial regulatory (homeobox) gene activity.
(2) subsequent activity of two regulatory molecular groups:
Growth factor families and steroid/thyroid family.

56. • It is claimed that regulatory molecules can
(1) "alter the manner in which homeobox genes coordinate cell
migration and subsequent cell interactions that regulate
growth" and
(2) be involved in the "genetic variations causing, or
contributing to, the abnormal development of relatively
common craniofacial malformations.
Orthodontic implications
• poor co-ordination of form and size of structures(teeth and
jaws) by regulatory genes result in malocclusion and
dentofacial deformitites.

57. AJODO , 1997

58. EPIGENETIC ANTITHESIS
• • The epigenetic antithesis detailing the processes and
mechanisms seeking to clarify the casual chain between
genome & phenotype.
• • Process is a series of action or operation that had
towards a particular result.
• • Mechanism is a fundamental physical or chemical
process involved in, or responsible for an action, reaction
or other nailed phenomenon.

59. Epigenetic process of loading -many different mechanism are
capable of modifying phenotype.
1. Loads may act at - cellular level or tissue level
2. Loads may be – dynamic or Static
3. To be effective load may increase,decrease or remain constant
 Epigenetic mechanism at cellular level-
1. Deformation of extracellular matrix.
2. Altering the cell shape.
• Epigenetic regulation at higher level- Regulation of periosteal
matrices.

60. A RESOLVING SYNTHESIS
• • It argues that morphogenesis is regulated by the activity of
both genomic and epigenetic processes and mechanisms.
• • Both are necessary causes; neither alone are sufficient
causes; and only their integrated activities provides the
necessary and sufficient causes of growth and development.
• • Genomic factors are considered as intrinsic and prior
causes;
• • epigenetic factors are considered as extrinsic and proximate
causes.

61. •Complex adaptive system
• Ensemble of several tissue and organs.
• Cas processes genomic and epigenetic information in parallel
manner.
• Minor changes in epigenetic input result in huge fluctuation in
morphogenetic output.

62. • • Ontogeny is a nonlinear process.
• • Spontaneous self organising ontogenic processes and
mechanism can create phenotypic variability under
constant genetic and other extra organismal epigenetic
condition.

63. • • OPERATION OF COMPLEXITY can be suggested as-
• "environmental factors thus play a decisive role in all
ontogenetic processes. But it is the organism itself that, as
an integrated system, dictates the nature of each and every
developmental response, the living organism self-organizes
on the basis of its own internal structuring, in continuous
interaction with the environment in which it finds itself.”

64. CONCLUSION
• Genomic and epigenetic processes are examples of
totally differing types of causation genomic formal cause
and epigenetic efficient cause.
• Individually both are necessary causes, but neither are
sufficient causes alone. Together they provide both the
necessary and sufficient causes for the control
(regulation) of morphogenesis.
• Epigenetic processes and events are the immediately
proximate causes of development, and as such they are
the primary agencies.

65. SUMMARY

66. Functional cranial
component
SKELETAL UNIT FUNCTIONAL
MATRIX
MACROSKELE
TAL
EX:
MANDIBLE
MAXILLA
MICROSKELE
TAL
Ex: coronoid,
angular,
alveolar,basal,
Orbital,
pneumatic,
palatal , basal
Periosteal ex:
muscles,
glands,
nerves,
vessels , fat
Capsular
ex:
neurocrania
l , orofacial

67. • Functional matrix hypothesis is a series of 4 articles
given by melvin moss in 1997:
• 1- the role of mechanotransduction
• 2- the role of osseous connected cellular network
• 3- the genomic thesis
• 4- the epigenetic antithesis and resolving synthesis.

68. THE ROLE OF MECHANOTRANSDUCTION
THE ROLE OF OSSEOUS CONNECTED CELLULAR NETWORK
(1997)
enable a cell to sense and To
respond to extrinsic surrounding
transmits extracellular physical
Stimulus to receptor cell
transforms stimulus information
Into intracellular signal
Loading
static dynamic
mechanosensing
mechanoreception
mechanotransduction

69. (Transmits information
From strained matrix
To bone cell nuclear
Membrane)
mechanotransduction
Ionic/electrical mechanical
Stretch
activate
d
channel
s
Electro-
mechanic
al
electro
kinetic
Field
strength
Macromolecula
r level
Skeletal signal
growth
CCN
Response
deposition
resorption
maintainanc
e

70. THE GENOMIC THESIS (1997)
• The genomic thesis holds that the genome, contains all
the information needed for growth and development of
an organism from intrauterine life to senescence.
• This theory argue that all (phenotype) features are
ultimately determined by dna sequence of genome.

71. THE EPIGENETIC ANTITHESIS AND THE
RESOLVING SYNTHESIS
(1997)
• Both the genomic (intrinsic, prior) and epigenetic
(extrinsic, proximate) factors are each a necessary
cause, but neither alone is a sufficient cause. Only the
interaction of both provides both the necessary and
sufficient cause of morphogenesis.

72. THANKYOU