FUNCTIONAL MATRIX
THEORY REVISITED
BY
Dr. Gejo Johns
Dept of orthodontics
contents
 Functional matrix theory
 Constrains of FMH
 Functional matrix theory revisited
 Articles
 Reference
Functional Matrix Hypothesis-Melvin L.
Moss 1962
 Revisited –1997
 FMH 1
 FMH 2
 FMH 3
 FMH 4
( Am J Orthod Dentofac Orthop 1997;112)
Functional matrix theory
 The functional matrix hypothesis claims that the origin ,
growth & 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 non-skeletal tissues, organs
or functioning spaces.
 Functional cranial component
Skeletal unit Functional matrix
Macroskeletal
Eg:endocranial
surface Of calvari
Microskeletal
Eg:coronoid,
angular
Periosteal
E:-teeth and
muscles
Capsular
matrix
neurocranial orofacial
 The periosteal matrices stimulation causes
growth of the microskeletal unit .They act to
alter the size or shape or both of the bones.
The growth process that occurs due to
periosteal matrix stimulation are called
‘Transformation”
 The capsular matrix act indirectly on
macroskeletal unit or entire functional cranial
component . They do not alter the size and
shape of the skeletal unit they change their
location in space this is called ‘Translation’.
Drawbacks of functional matrix
theory
No clarification on how functional needs are
transmitted to tissues - PROFITT
MOSS -
 Methodological constraints
 Hierarchical constraints
Methodological constraints
 FMH uses macroscopic measurements by
using point mechanics and arbitary reference
frames like cephalometric radiograph.
 Measurement technique and arbitary
reference planes are now beeen replaced by
continuum mechanics technique like –FEM
Hierarchical constraints
 Second constraint of FMH doesn’t explain
how the extrinsic , epigenetic functional matrix
stimuli are transduced into regulatory signals
at the cellular, multicellular or molecular levels
 FMH versions were suspended or
sandwiched as it were between these two
hierarchical levels
 Experimental and theorical studies of bone
adaptation consider only the unicellular ,
unimolecular or ,unigenomic levels not
extensible to higher multicellular , tissue levels.
 The new version of FMH tries to bridge the gap
between hierarchial constraints and explain the
operation from genome to organ level
 The newest FMH version includes two
complementary concepts
1. Mechanotransduction occur in single cell
2. Connected cellular network
Mechanotransduction
 Mechanotransduction is the process by which
mechanical stimulus is converted into biological
signal to alter a cellular response
 Mechanosensing processes enables a cell to
sense and response to extrinsic loadings, a
widespread biologic attribute by using the
process of mechanoreception
Osseous Mechanotransduction
 Static and dynamic loadings are continuously
applied to bone tissue tending to deform both
extracellular matrix and bone cells
 When an appropriate stimulus exceeds
threshold values the loaded tissue responds
by bone cell adaptation processes.
 Both osteocytes and osteoblasts are
competent for intracellular stimulus reception
and transduction and subsequent intracellular
signal transmission.
 Osteoblast directly regulate bone deposition
and maintenance and indirectly regulate
osteoclastic resorption
 Osseous mechanotransduction is unique in four
ways
1. Most other mechanosensory cells are
cytologically specialized ,but bone cells are
not.
2. One bone loading stimulus can evoke three
adaptational response ,whereas non-osseous
processes generally evoke one
3. Osseous signal transmission is aneural,
whereas all other mechanosensational
signals use afferent neural pathways
4. The evoked bone adaptational response are
confined within each bone organ
independently.
Types of mechanotrasnductive
processes
1.IONIC-brought about transport of ions through
plasma membrane resulting in creation of electrical
signal.
2.Stretch activated channels
loading S-A get activated passage of certain
sized ions k+,ca2+, Na+
3. Electrical processes
 Electromechanical
 Electro kinetic
 Electric field strength
4 Mechanical process
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 intracellulary with
cytoskeletal actin
• Macromolecular lever capable of transmitting information from
strained matrix to bone cell nuclear membrane
extracellular
intracellular
Macromolecular collagen
Transmembrane integrin
Cytoskeletal actin
Nuclear membrane
Organic matrix
 The first article implicate the ability of bone
cells to carry out intacellular
mechanosensation and transduction and intra
cellular network communication
FMHR# 2 The role of osseous
connected cellular network (CCN)
 Bone as an osseous connected cellular network
(CCN).
 All bones are extensively interconnected by gap
junction and form an osseous connective cellular
network
Osteocytes have cytoplasmic processes which are
oriented three dimensionally
GAP JUNCTION- are found where plasma
membrane of pair of markedly overlapping
cannicular process meet
 Canaliculi form extensive connection between
osteons and interstitial region
Gap junction connect
 Superficial osteocytes to periosteal and
endosteal osteoblast
 Periosteal osteoblast with preosteblastic cells
and these in turn are similarly interconnected
Gap junction
Bone as CCN
 Network theory
 Cells are arranged in 3 layers
Initial input layer
Final output layer
Intermediate / hidden layer
Signal transmission
FNH#2 CONCLUSION
 The FMH concept 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 upwards
again through histologic levels to the
event of gross bone form adaptational
changes
 The initial version of FMH claiming epigenetic
control of morphogenesis.
 Current – genomic regulation of growth
The Genomic thesis
 The genomic thesis holds that from the
moment of fertilization all the information
necessary for the regulation is determined by
the DNA
 It includes regulation of intranuclear formation
and transcription of mRNA.
 It is the genome of an individual which
determines the overall phenotype
APPLICATION OF GENOMIC
THESIS IN OROFACIAL BIOLOGY
 10%-of the genome is related to the
phenotypic ontogenesis
Prenatal craniofacial development is controlled
by two processes-
1.Initial Regulatory gene activity.
2.Subsequent activity of the regulatory
molecular groups such as growth factory
families and steroid/ thyroid/retinoic acid
super family.
CAUSATION
 There is continuing controversy concerning
the role of genomic and non genomic
processes in the regulation of growth this is
resolved by several types of causation.
CLASSISAL CATEGORISATION OF
CAUSATION
There are four principle causes of ontogenesis
 MATERIAL(what is acted upon?)
 FORMAL(set of rules?)
 EFFICIENT(immediate preceding event?)
 FINAL( why)
 MATERIAL: Cellular and extracellular
substance, extrinsic and intrinsic
 FORMAL: Genomic regulation
 EFFICIENT: Epigenetic event
 FINAL : Teleology
 The genomic thesis is denied because it is
reductionist and molecular
 Descriptions of the causation of all
hierarchically higher and structurally more
complex morphogenetic processes are
reduced to explanation of mechanisms at the
molecular (DNA) level.
THE EPIGENETIC ANTITHESIS
Refers to to the entire series of interaction
among cells and cell products which lead to
morphogenesis and differentiation
THESE INCLUDE-
1. All extrinsic, extraorganismal,
macroenvironment factors
2. All intrinsic, intraorganismal,
microenviromental factors
COMPLEXITY AND SELF
ORGANISATION
 Complex adaptive system ensembles of
several tissues and organs, and not as
clusters of individual cells and extracellular
substances
 Ontogeny is a nonlinear process.
 Spontaneous self organizing ontogenic
processes and mechanism can create
phenotypic variability under constant genetic
and other extra organisimal epigenetic
condition.
“Environmental factors 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 a very 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
ARTICLES
References
 The functional matrix hypothesis revisited.1.
The role of mechanotransduction – Moss; Am
J Orthod Dentofac Orthop 1997; 112:8-11
 The functional matrix hypothesis revisited.
2.The role of an osseous connected
cellular network – Moss; Am J Orthod
Dentofac Orthop 1997;112:221-6
 The functional matrix hypothesis revisited.3.The
genomic thesis – Moss; Am J Orthod Dentofac
Orthop 1997; 112:338-42
 The functional matrix hypothesis revisited.4.The
epigenetic antithesis & the resolving synthesis –
Moss; Am J Orthod Dentofac Orthop 1997;
112:410-17
 Moss ML. The functional matrix. In: Kraus B,
Reidel R, editors. Vistas inorthodontics.
Philadelphia: Lea & Febiger, 1962:85-98.
 Moss ML. The primacy of functional matrices in
orofacial growth. Trans Br Soc Study Orthod and Dent
Pract 1968;19:65-73.
 Moss ML. Twenty years of functional cranial analysis.
Am J Orthod 1972;61:479-85.
 Moss ML, Salentijn L. The primary role of functional
matrices in facial growth.Am J Orthod 196%;55:566-
77.
 Moss ML, Salentijn L. The capsular matrix. Am J
Orthod 1969b;56:474-90.
 Moss ML. The functional matrix hypothesis revisited.
1. The role of mechanotransduction.Am J Orthod
Dentofac Orthop 1997;111:8-11.
Functional matrix revisited

Functional matrix revisited

  • 1.
    FUNCTIONAL MATRIX THEORY REVISITED BY Dr.Gejo Johns Dept of orthodontics
  • 2.
    contents  Functional matrixtheory  Constrains of FMH  Functional matrix theory revisited  Articles  Reference
  • 3.
    Functional Matrix Hypothesis-MelvinL. Moss 1962  Revisited –1997  FMH 1  FMH 2  FMH 3  FMH 4 ( Am J Orthod Dentofac Orthop 1997;112)
  • 4.
    Functional matrix theory The functional matrix hypothesis claims that the origin , growth & 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 non-skeletal tissues, organs or functioning spaces.
  • 5.
     Functional cranialcomponent Skeletal unit Functional matrix Macroskeletal Eg:endocranial surface Of calvari Microskeletal Eg:coronoid, angular Periosteal E:-teeth and muscles Capsular matrix neurocranial orofacial
  • 7.
     The periostealmatrices stimulation causes growth of the microskeletal unit .They act to alter the size or shape or both of the bones. The growth process that occurs due to periosteal matrix stimulation are called ‘Transformation”  The capsular matrix act indirectly on macroskeletal unit or entire functional cranial component . They do not alter the size and shape of the skeletal unit they change their location in space this is called ‘Translation’.
  • 9.
    Drawbacks of functionalmatrix theory No clarification on how functional needs are transmitted to tissues - PROFITT MOSS -  Methodological constraints  Hierarchical constraints
  • 10.
    Methodological constraints  FMHuses macroscopic measurements by using point mechanics and arbitary reference frames like cephalometric radiograph.  Measurement technique and arbitary reference planes are now beeen replaced by continuum mechanics technique like –FEM
  • 11.
    Hierarchical constraints  Secondconstraint of FMH doesn’t explain how the extrinsic , epigenetic functional matrix stimuli are transduced into regulatory signals at the cellular, multicellular or molecular levels  FMH versions were suspended or sandwiched as it were between these two hierarchical levels
  • 12.
     Experimental andtheorical studies of bone adaptation consider only the unicellular , unimolecular or ,unigenomic levels not extensible to higher multicellular , tissue levels.  The new version of FMH tries to bridge the gap between hierarchial constraints and explain the operation from genome to organ level
  • 13.
     The newestFMH version includes two complementary concepts 1. Mechanotransduction occur in single cell 2. Connected cellular network
  • 16.
    Mechanotransduction  Mechanotransduction isthe process by which mechanical stimulus is converted into biological signal to alter a cellular response  Mechanosensing processes enables a cell to sense and response to extrinsic loadings, a widespread biologic attribute by using the process of mechanoreception
  • 18.
    Osseous Mechanotransduction  Staticand dynamic loadings are continuously applied to bone tissue tending to deform both extracellular matrix and bone cells  When an appropriate stimulus exceeds threshold values the loaded tissue responds by bone cell adaptation processes.  Both osteocytes and osteoblasts are competent for intracellular stimulus reception and transduction and subsequent intracellular signal transmission.
  • 19.
     Osteoblast directlyregulate bone deposition and maintenance and indirectly regulate osteoclastic resorption  Osseous mechanotransduction is unique in four ways 1. Most other mechanosensory cells are cytologically specialized ,but bone cells are not. 2. One bone loading stimulus can evoke three adaptational response ,whereas non-osseous processes generally evoke one
  • 20.
    3. Osseous signaltransmission is aneural, whereas all other mechanosensational signals use afferent neural pathways 4. The evoked bone adaptational response are confined within each bone organ independently.
  • 21.
    Types of mechanotrasnductive processes 1.IONIC-broughtabout transport of ions through plasma membrane resulting in creation of electrical signal. 2.Stretch activated channels loading S-A get activated passage of certain sized ions k+,ca2+, Na+ 3. Electrical processes  Electromechanical  Electro kinetic  Electric field strength 4 Mechanical process
  • 22.
    Mechanical process  Thebasis 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 intracellulary with cytoskeletal actin
  • 23.
    • Macromolecular levercapable of transmitting information from strained matrix to bone cell nuclear membrane extracellular intracellular Macromolecular collagen Transmembrane integrin Cytoskeletal actin Nuclear membrane Organic matrix
  • 25.
     The firstarticle implicate the ability of bone cells to carry out intacellular mechanosensation and transduction and intra cellular network communication
  • 26.
    FMHR# 2 Therole of osseous connected cellular network (CCN)  Bone as an osseous connected cellular network (CCN).  All bones are extensively interconnected by gap junction and form an osseous connective cellular network Osteocytes have cytoplasmic processes which are oriented three dimensionally GAP JUNCTION- are found where plasma membrane of pair of markedly overlapping cannicular process meet
  • 27.
     Canaliculi formextensive connection between osteons and interstitial region Gap junction connect  Superficial osteocytes to periosteal and endosteal osteoblast  Periosteal osteoblast with preosteblastic cells and these in turn are similarly interconnected
  • 28.
  • 29.
    Bone as CCN Network theory  Cells are arranged in 3 layers Initial input layer Final output layer Intermediate / hidden layer
  • 30.
  • 31.
    FNH#2 CONCLUSION  TheFMH concept 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 upwards again through histologic levels to the event of gross bone form adaptational changes
  • 33.
     The initialversion of FMH claiming epigenetic control of morphogenesis.  Current – genomic regulation of growth
  • 34.
    The Genomic thesis The genomic thesis holds that from the moment of fertilization all the information necessary for the regulation is determined by the DNA  It includes regulation of intranuclear formation and transcription of mRNA.  It is the genome of an individual which determines the overall phenotype
  • 35.
    APPLICATION OF GENOMIC THESISIN OROFACIAL BIOLOGY  10%-of the genome is related to the phenotypic ontogenesis Prenatal craniofacial development is controlled by two processes- 1.Initial Regulatory gene activity. 2.Subsequent activity of the regulatory molecular groups such as growth factory families and steroid/ thyroid/retinoic acid super family.
  • 36.
    CAUSATION  There iscontinuing controversy concerning the role of genomic and non genomic processes in the regulation of growth this is resolved by several types of causation.
  • 37.
    CLASSISAL CATEGORISATION OF CAUSATION Thereare four principle causes of ontogenesis  MATERIAL(what is acted upon?)  FORMAL(set of rules?)  EFFICIENT(immediate preceding event?)  FINAL( why)
  • 38.
     MATERIAL: Cellularand extracellular substance, extrinsic and intrinsic  FORMAL: Genomic regulation  EFFICIENT: Epigenetic event  FINAL : Teleology
  • 41.
     The genomicthesis is denied because it is reductionist and molecular  Descriptions of the causation of all hierarchically higher and structurally more complex morphogenetic processes are reduced to explanation of mechanisms at the molecular (DNA) level.
  • 42.
    THE EPIGENETIC ANTITHESIS Refersto to the entire series of interaction among cells and cell products which lead to morphogenesis and differentiation THESE INCLUDE- 1. All extrinsic, extraorganismal, macroenvironment factors 2. All intrinsic, intraorganismal, microenviromental factors
  • 43.
    COMPLEXITY AND SELF ORGANISATION Complex adaptive system ensembles of several tissues and organs, and not as clusters of individual cells and extracellular substances  Ontogeny is a nonlinear process.  Spontaneous self organizing ontogenic processes and mechanism can create phenotypic variability under constant genetic and other extra organisimal epigenetic condition.
  • 44.
    “Environmental factors playa decisive role in all ontogenetic processes. But it is the organism itself that ,as an integrated system ,dictates the nature of each and a very 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
  • 45.
  • 49.
    References  The functionalmatrix hypothesis revisited.1. The role of mechanotransduction – Moss; Am J Orthod Dentofac Orthop 1997; 112:8-11  The functional matrix hypothesis revisited. 2.The role of an osseous connected cellular network – Moss; Am J Orthod Dentofac Orthop 1997;112:221-6
  • 50.
     The functionalmatrix hypothesis revisited.3.The genomic thesis – Moss; Am J Orthod Dentofac Orthop 1997; 112:338-42  The functional matrix hypothesis revisited.4.The epigenetic antithesis & the resolving synthesis – Moss; Am J Orthod Dentofac Orthop 1997; 112:410-17  Moss ML. The functional matrix. In: Kraus B, Reidel R, editors. Vistas inorthodontics. Philadelphia: Lea & Febiger, 1962:85-98.
  • 51.
     Moss ML.The primacy of functional matrices in orofacial growth. Trans Br Soc Study Orthod and Dent Pract 1968;19:65-73.  Moss ML. Twenty years of functional cranial analysis. Am J Orthod 1972;61:479-85.  Moss ML, Salentijn L. The primary role of functional matrices in facial growth.Am J Orthod 196%;55:566- 77.  Moss ML, Salentijn L. The capsular matrix. Am J Orthod 1969b;56:474-90.  Moss ML. The functional matrix hypothesis revisited. 1. The role of mechanotransduction.Am J Orthod Dentofac Orthop 1997;111:8-11.