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FUNCTIONAL MATRIX HYPOTHESIS AND
FUNCTIONAL MATRIX - REVISITED
1
Presented by:
Dr. Vidhi R. Shah
1st Year Pg
Dr. MELVIN L. MOSS
(1960s)
CONTENTS
• Introduction
• History
• Definition
• Functional matrix concept
• Functional matrix analysis
• Constraints of FMH
• Conceptual and Anatomic bases of revised FMH
• Role of Mechanotransduction
• Role of an Osseous connected cellular network
• The Genomic thesis
• The Epigenetic antithesis and the resolving synthesis
• Conclusion
• References
2
INTRODUCTION
3
HISTORY OF FMH
4
DEFINITION
5
The functional matrix hypothesis claims that the origin, growth and
maintenance of all skeletal tissues and organs are always secondary,
compensatory and mechanically obligatory responses to temporally
and operationally prior events or processes the occur in specifically
related non-skeletal tissues, organ or functioning spaces.
Orthodontics – The Art and Science – S.I.Bhalajhi - 5th Edition
FUNCTIONAL MATRIX CONCEPT
• Skeletal Tissues
6
Non-Skeletal Tissues
• Whatever changes are happening in skeletal tissues
which is responsible due to non-skeletal tissues
(Functional matrix).
Functional Cranial Component
Functional matrix Skeletal unit
7
Bone, Cartilage,
Tendinous
Tissue
Muscles, tissues,
organs, spaces,
glands, vessels
8
Functional cranial component
Skeletal unit Functional matrices
Macro skeletal
E.g.-endocranial
surface Of calvaria,
Maxilla, Mandible
Micro skeletal
E.g.-coronoid,
Angular, Condyle,
Alveolar, Basal
Periosteal
E.g.-teeth,
Muscles,
Nerves, Glands
Capsular matrix
Neuro-cranial
capsule
Oro-facial
capsule
The differential roles of periosteal and capsular functional matrices in orofacial growth -Melvin L. Moss
European Journal of Orthodontics, Volume 29, Issue suppl_1, April 2007, Pages i96–i101
PERIOSTEAL MATRICES
9
CAPSULAR MATRIX
Directly ;
Actively
Micro- skeletal unit
Transformation
Indirectly;
passively
Macro- skeletal unit
Translation
- Change in the size and the
position of the skeletal units.
“Bone Deposition and
Resorption”
- Expansion of the bone
Periosteal matrix
10
Capsular matrix
11
Moss and Salentijn, AJO 1969;20-31
• Neurocranial capsules
• Orofacial capsules
The Functional Matrix Hypothesis
• Growth of cranial vault as a direct response to growth of
the brain.
12
Contemporary Orthodontics by William R. Proffit, 6th edition.
13
Textbook of Craniofacial Growth – Sridhar Premkumar 1St edition.
LIMITATIONS OF FMH:-
• Moss contends - growth sites but not growth centres.
• No direct genetic influence – size,
shape,
position
14
Moss ML. The functional matrix hypothesis revisited, 1.The role of mechanotransduction. Am J Orthod
Dentofac Orthop 1997;112:8-11
WHY FMH – REVISITED DEVELOPED?
• Advances in the biomedical, bioengineering and computer
sciences.
• Recent work on two topics :-
1) Cellular transduction of informational signals.
2) Biologic cellular network theory.
15
Moss ML. The functional matrix hypothesis revisited, 1.The role of mechanotransduction. Am J Orthod
Dentofac Orthop 1997;112:8-11
CONCEPTUALAND ANATOMIC BASIS
OF THE REVISED FMH
Histologic Studies show-
• Deposition, Resorption and
maintenance – by homologous
osteoblasts
16
Moss ML. The functional matrix hypothesis revisited, 1.The role of mechanotransduction. Am J Orthod
Dentofac Orthop 1997;112:8-11
CONCEPTUALAND ANATOMIC
BASIS OF THE REVISED FMH
Includes the molecular and cellular processes underlying
the triad of active skeletal growth processes.
17
Deposition
Maintenance
Resorption
Moss ML. The functional matrix hypothesis revisited, 1.The role of mechanotransduction. Am J Orthod Dentofac
Orthop 1997;112:8-11
CONSTRIANTS OF FMH
- Qualitative description
- Growth at gross anatomic level.
- There is no clarification on how functional needs are
transmitted to tissues.
 The two explanatory constraints of FMH are:
1. METHODOLOGICAL CONSTRAINT
2. HIERARCHIAL CONSTRAINT
18
Moss ML. The functional matrix hypothesis revisited, 1.The role of mechanotransduction. Am J Orthod Dentofac
Orthop 1997;112:8-11
METHODOLOGICAL CONSTRAINT
Macroscopic measurements techniques:-
1) Point mechanics
2) Arbitrary reference frames
Eg: Roentgenographic Cephalograms
Only method specific descriptions, No structural
detail.
Constraint was removed by the continuum mechanics
techniques of finite element method.
Quantitative aspects of localized cephalic growth kinematics.
19
Moss ML. The functional matrix hypothesis revisited, 1.The role of mechanotransduction. Am J Orthod Dentofac
Orthop 1997;112:8-11
HIERARCHIAL CONSTRAINT
1) Did not extend - downwards or upwards.
2) Could not describe how extrinsic epigenetic FM stimuli are
transduced into regulatory signals by individual bone cells.
3) Bone adaptation by - unicellular, unimolecular, or
epigenomic levels.
20
Moss ML. The functional matrix hypothesis revisited, 1.The role of mechanotransduction. Am J Orthod Dentofac
Orthop 1997;112:8-11
21
Genome
Organ
The Functional Matrix Hypothesis :
Revisited (1990s)
Moss ML. The functional matrix hypothesis revisited, 1.The role of mechanotransduction. Am J Orthod
Dentofac Orthop 1997;112:8-11
HOW TO OVERCOME HIERARCHIAL
CONSTRAINT
Four Complementary concepts
22
Moss ML. The functional matrix hypothesis revisited, 1.The role of mechanotransduction. Am J Orthod Dentofac
Orthop 1997;112:8-11
 FUNCTIONAL MATRIX HYPOTHESIS REVISITED-1
THE ROLE OF MECHANOTRANSDUCTION
23
FUNTIONAL MATRIX HYPOTHESIS - Revisited
Moss ML. The functional matrix hypothesis revisited, 1.The role of mechanotransduction. Am J Orthod Dentofac
Orthop 1997;112:8-11
MECHANOSENSING
All vital cells are irritable and respond to alterations in their
external environment.
Mechanosensing - Enables a cell to sense and respond to
extrinsic loadings by using two processes.
MECHANORECEPTION MECHANOTRANSDUCTION
24
Moss ML. The functional matrix hypothesis revisited, 1.The role of mechanotransduction. Am J
Orthod Dentofac Orthop 1997;112:8-11
MECHANOTRANSDUCTION
Extra-cellular Stimulus Stimulus is Energy
TRANSMITTED TRANSFORMED/TRANSDUCED
RECEPTOR
CELL
SIGNAL in
Intracellular
MECHANORECEPTION MECHANOTRANSDUCTION
VITAL CELLS
Irritable (External
Environment)
Mechanosensing Process
Moss ML. The functional matrix hypothesis revisited, 1.The role of mechanotransduction. Am J Orthod Dentofac
Orthop 1997;112:8-11
OSSEOUS MECHANOTRANSDUCTION
Triad of bone cell adaptation process
occurs
When appropriate stimulus exceeds
threshold values
Deform extracellular matrix and bone cells
Static and dynamic loads continuously
applied to bone tissues
Multiscale modeling of bone tissue
mechanobiology, Bone 151 (2021) 116032
26
Load
Moss ML. The functional matrix hypothesis revisited, 1.The role of mechanotransduction. Am J Orthod
Dentofac Orthop 1997;112:8-11
Intracellular
stimulus
reception
Intercellular
signal
transmission
Transduction
Osteoblasts
Directly regulate
bone deposition
and maintenance
Osteoblasts
Indirectly
regulate
osteoclastic
resorption
Triad of Bone
cell Adaptation
OSSEOUS MECHANOTRANSDUCTION
27
Moss ML. The functional matrix hypothesis revisited, 1.The role of mechanotransduction. Am J Orthod
Dentofac Orthop 1997;112:8-11
RANKL
RANK
OSSEOUS MECHANOTRANSDUCTION
- Osseous mechanotransduction is unique in four ways:
28
1) bone cells are not - cytologically specialized
2) Stimulus can evoke - three
adaptational Responses
3) Osseous signal transmission is aneural.
4) Adaptational responses
"bone organ"
independently.
Moss ML. The functional matrix hypothesis revisited, 1.The role of mechanotransduction. Am J Orthod Dentofac
Orthop 1997;112:8-11
29
Moss ML. The functional matrix hypothesis revisited, 1.The role of mechanotransduction. Am J
Orthod Dentofac Orthop 1997;112:8-11
Flow chart of FMH
Types of mechanotransductive processes
30
1. Ionic –
2. Stretch activated channels –
3. Electrical processes -
4. Mechanical process -
- Translate the information - periosteal functional matrix
stimulus into skeletal cell signal.
Moss ML. The functional matrix hypothesis revisited, 1.The role of mechanotransduction. Am J
Orthod Dentofac Orthop 1997;112:8-11
STRETCH ACTIVATED CHANNELS
Deformation in strained bone tissue
Plasma stretch activated ion
channels
Permit passage of certain ions-
K+,Ca++,Na++
Ionic flow in turn initiates
intracellular electrical events
31
Moss ML. The functional matrix hypothesis revisited, 1.The role of mechanotransduction. Am J Orthod
Dentofac Orthop 1997;112:8-11
Extracellular matrix
ELECTRICAL PROCESS :
1) ELECTROMECHANICAL
voltage-activated ion channels.
Transmembrane ionic flow
Osseous transductive process.
Ionic flows generate osteocytic action
potentials.
32
Moss ML. The functional matrix hypothesis revisited, 1.The role of mechanotransduction. Am J Orthod
Dentofac Orthop 1997;112:8-11
ELECTRICAL PROCESS :
ELECTROKINETIC
 Bond and unbound electrical charges
 Streaming potential (SP) origin.
Conservation of electrical charges in
deformed bone.
SGP of ±2 mV can initiate osteogenesis and
osteocytic action potentials.
33
Moss ML. The functional matrix hypothesis revisited, 1.The role of mechanotransduction. Am J Orthod Dentofac
Orthop 1997;112:8-11
ELECTRICAL PROCESS :
ELECTRIC FIELD STRENGTH
Extrinsic parameters are unclear.
A significant parallel exists between
the exogenous and endogenous field’s
parameters.
Bone responds to exogenous electric
fields in an effective range of 1 to 10
µV/cm.
34
Moss ML. The functional matrix hypothesis revisited, 1.The role of mechanotransduction. Am J
Orthod Dentofac Orthop 1997;112:8-11
MECHANICAL PROCESSES
 Hierarchically lower level bone cell
genomic function.
 Strain/deformation in the extra cellular
bone matrix - transmitted
Intracellularly via Mechanical levers.
35
Moss ML. The functional matrix hypothesis revisited, 1.The role of mechanotransduction. Am J Orthod
Dentofac Orthop 1997;112:8-11
FUNCTIONAL MATRIX HYPOTHESIS
REVISITED-2
(THE ROLE OF OSSEOUS CONNECTED CELLULAR
NETWORK)
• Bone cells to carry out - mechano-sensation and
transduction.
Moss ML. The functional matrix hypothesis revisited, 2.The role of an osseous connected cellular network.Am J
Orthod Dentofac Orthop 1997 36
GAP JUNCTIONS
Role of osseous connected cellular network(CCN)
37
Moss ML. The functional matrix hypothesis revisited, 2.The role of an osseous connected cellular
network.Am J Orthod Dentofac Orthop 1997
BONE AS AN OSSEOUS CCN
• In the Network theory; Cells are arranged in 3 layers :-
1) Initial input layer
2) Intermediate / Hidden layer
3) Final output layer
38
Moss ML. The functional matrix hypothesis revisited, 2.The role of an osseous connected cellular
network.Am J Orthod Dentofac Orthop 1997
PROCESS OF NETWORK THEORY
Loadings within each cell independently
Cells in INITIAL layer receive several stimuli
(weighted input)
All stimuli (weighted inputs) are summed up
If the value is greater than threshold value
An intracellular signal is generated/
Mechanotransduction occurs
39
INITIAL INPUT
Moss ML. The functional matrix hypothesis revisited, 2.The role of an osseous connected cellular
network.Am J Orthod Dentofac Orthop 1997
PROCESS OF NETWORK THEORY
HIDDEN LAYER
Signal transmitted by gap junctions to HIDDEN LAYER cells (adjacent
osteocytes)
Similar process of stimuli (weighted signal) summation, comparison,
transmission occur
Signal reaches Osteoblasts
40
Moss ML. The functional matrix hypothesis revisited, 2.The role of an osseous
connected cellular network.Am J Orthod Dentofac Orthop 1997
PROCESS OF NETWORK THEORY
FINAL OUTPUT
Osteoblasts reach the final layer
Outputs of these anatomically superficial cells determines the
Site, rate, direction, magnitude, duration of the specific adaptive
response,
i.e. deposition, resorption, and/or maintenance, of each cohort of
osteoblasts.
41
Moss ML. The functional matrix hypothesis revisited, 2.The role of an osseous
connected cellular network.Am J Orthod Dentofac Orthop 1997
Attributes of CCN
42
1) Developmentally -
2) Operationally –
3) Structurally -
Moss ML. The functional matrix hypothesis revisited, 2.The role of an osseous
connected cellular network.Am J Orthod Dentofac Orthop 1997
FUNCTIONAL MATRIX HYPOTHESIS
REVISITED-3
(THE GENOMIC THESIS)
• The initial version of FMH - was based on macroscopic
experimental level.
43
The functional matrix hypothesis revisited. 3. The genomic thesis,Am J Orthod Dentofacial Orthop, 1997 Sep;112(3):338-
42.
Recent version – hierarchically upward, microscopic level
and mechanism of gene expression.
The genomic thesis
Initial regulatory
(homeobox) gene
activity
44
The functional matrix hypothesis revisited. 3. The genomic thesis,Am J Orthod Dentofacial Orthop, 1997
Sep;112(3):338-42.
• In orofacial biology ,
Prenatal craniofacial
development is
controlled by two
process :-
• DNA - from the moment of fertilization all the
information necessary for the regulation
• It includes regulation of intranuclear formation and
transcription of mRNA.
• It is the genome of an individual which determines the
overall phenotype.
Subsequent activity
of the regulatory
molecular groups
45
The Biology primer – Jason Walker
FUNCTIONAL MATRIX
HYPOTHESIS REVISITED-4
(The epigenetic antithesis and the resolving
synthesis)
46
The functional matrix hypothesis revisited. 4. The epigenetic antithesis and the resolving synthesis, Am J Orthod
Dentofacial Orthop, 1997 Oct;112(4):410-7.
THE EPIGENETIC ANTITHESIS
• It refers to the entire series of interaction among cells and
cell products which lead to morphogenesis and
differentiation.
Process :-
Mechanism :-
47
The functional matrix hypothesis revisited. 4. The epigenetic antithesis and the resolving
synthesis, Am J Orthod Dentofacial Orthop, 1997 Oct;112(4):410-7.
Epigenetic process of loading
• Many different mechanism are capable of modifying
phenotype.
1) Loads may act at – Cellular and Tissue level
2) Loads may be – Dynamic and Static
3) To be effective load may increase, decrease or remain
constant.
48
The functional matrix hypothesis revisited. 4. The epigenetic antithesis and the
resolving synthesis, Am J Orthod Dentofacial Orthop, 1997 Oct;112(4):410-7.
A RESOLVING SYNTHESIS
Morphogenesis
Genomic factors
Intrinsic
Prior
Causes
Epigenetic factors
Extrinsic
Proximate
Causes
49
It provides
the
necessary
and
sufficient
causes of
growth and
development
The functional matrix hypothesis revisited. 4. The epigenetic antithesis and the
resolving synthesis, Am J Orthod Dentofacial Orthop, 1997 Oct;112(4):410-7.
CLASSICAL CATEGORISATION OF
CAUSATION
• There are four principles causes of ontogenesis :-
Material :- (What is act upon?)
Formal :- ( Set of rules?)
Efficient :- (Immediate preceding event?)
Final :- ( Why?)
50
The functional matrix hypothesis revisited. 3. The genomic thesis,Am J Orthod Dentofacial
Orthop, 1997 Sep;112(3):338-42.
CONCLUSION
51
REFFERENCES
• Textbook of Craniofacial Growth – Sridhar Premkumar 1St edition.
• Orthodontics – The Art and Science - 5th Edition – S. I. Bhalajhi
• The differential roles of periosteal and capsular functional matrices
in orofacial growth – Melvin L. Moss – European Journal Of
Orthodontics, Volume 29 – April 2007
• Multiscale modeling of bone tissue mechanobiology, Bone 151 (2021)
116032
• Moss ML. The functional matrix hypothesis revisited, 1.The role of
mechanotransduction. Am J Orthod Dentofac Orthop 1997;112:8-11
• Moss ML. The functional matrix hypothesis revisited, 1.The role of
mechanotransduction. Am J Orthod Dentofac Orthop 1997;112:8-11
• Moss ML. The functional matrix hypothesis revisited. 3. The
genomic thesis, Am J Orthop Dentofacial Orthop, 1997
Sep;112(3):338-42
• Moss ML. The functional matrix hypothesis revisited. 4. The
epigenetic antithesis and the resolving synthesis, Am J Orthod
Dentofacial Orthop, 1997 Oct;112(4):410-7.
52
THANK YOU !
53

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functional matrix- seminar in orthodonic

  • 1. FUNCTIONAL MATRIX HYPOTHESIS AND FUNCTIONAL MATRIX - REVISITED 1 Presented by: Dr. Vidhi R. Shah 1st Year Pg Dr. MELVIN L. MOSS (1960s)
  • 2. CONTENTS • Introduction • History • Definition • Functional matrix concept • Functional matrix analysis • Constraints of FMH • Conceptual and Anatomic bases of revised FMH • Role of Mechanotransduction • Role of an Osseous connected cellular network • The Genomic thesis • The Epigenetic antithesis and the resolving synthesis • Conclusion • References 2
  • 5. DEFINITION 5 The functional matrix hypothesis claims that the origin, growth and maintenance of all skeletal tissues and organs are always secondary, compensatory and mechanically obligatory responses to temporally and operationally prior events or processes the occur in specifically related non-skeletal tissues, organ or functioning spaces. Orthodontics – The Art and Science – S.I.Bhalajhi - 5th Edition
  • 6. FUNCTIONAL MATRIX CONCEPT • Skeletal Tissues 6 Non-Skeletal Tissues • Whatever changes are happening in skeletal tissues which is responsible due to non-skeletal tissues (Functional matrix).
  • 7. Functional Cranial Component Functional matrix Skeletal unit 7 Bone, Cartilage, Tendinous Tissue Muscles, tissues, organs, spaces, glands, vessels
  • 8. 8 Functional cranial component Skeletal unit Functional matrices Macro skeletal E.g.-endocranial surface Of calvaria, Maxilla, Mandible Micro skeletal E.g.-coronoid, Angular, Condyle, Alveolar, Basal Periosteal E.g.-teeth, Muscles, Nerves, Glands Capsular matrix Neuro-cranial capsule Oro-facial capsule The differential roles of periosteal and capsular functional matrices in orofacial growth -Melvin L. Moss European Journal of Orthodontics, Volume 29, Issue suppl_1, April 2007, Pages i96–i101
  • 9. PERIOSTEAL MATRICES 9 CAPSULAR MATRIX Directly ; Actively Micro- skeletal unit Transformation Indirectly; passively Macro- skeletal unit Translation - Change in the size and the position of the skeletal units. “Bone Deposition and Resorption” - Expansion of the bone
  • 11. Capsular matrix 11 Moss and Salentijn, AJO 1969;20-31 • Neurocranial capsules • Orofacial capsules
  • 12. The Functional Matrix Hypothesis • Growth of cranial vault as a direct response to growth of the brain. 12 Contemporary Orthodontics by William R. Proffit, 6th edition.
  • 13. 13 Textbook of Craniofacial Growth – Sridhar Premkumar 1St edition.
  • 14. LIMITATIONS OF FMH:- • Moss contends - growth sites but not growth centres. • No direct genetic influence – size, shape, position 14 Moss ML. The functional matrix hypothesis revisited, 1.The role of mechanotransduction. Am J Orthod Dentofac Orthop 1997;112:8-11
  • 15. WHY FMH – REVISITED DEVELOPED? • Advances in the biomedical, bioengineering and computer sciences. • Recent work on two topics :- 1) Cellular transduction of informational signals. 2) Biologic cellular network theory. 15 Moss ML. The functional matrix hypothesis revisited, 1.The role of mechanotransduction. Am J Orthod Dentofac Orthop 1997;112:8-11
  • 16. CONCEPTUALAND ANATOMIC BASIS OF THE REVISED FMH Histologic Studies show- • Deposition, Resorption and maintenance – by homologous osteoblasts 16 Moss ML. The functional matrix hypothesis revisited, 1.The role of mechanotransduction. Am J Orthod Dentofac Orthop 1997;112:8-11
  • 17. CONCEPTUALAND ANATOMIC BASIS OF THE REVISED FMH Includes the molecular and cellular processes underlying the triad of active skeletal growth processes. 17 Deposition Maintenance Resorption Moss ML. The functional matrix hypothesis revisited, 1.The role of mechanotransduction. Am J Orthod Dentofac Orthop 1997;112:8-11
  • 18. CONSTRIANTS OF FMH - Qualitative description - Growth at gross anatomic level. - There is no clarification on how functional needs are transmitted to tissues.  The two explanatory constraints of FMH are: 1. METHODOLOGICAL CONSTRAINT 2. HIERARCHIAL CONSTRAINT 18 Moss ML. The functional matrix hypothesis revisited, 1.The role of mechanotransduction. Am J Orthod Dentofac Orthop 1997;112:8-11
  • 19. METHODOLOGICAL CONSTRAINT Macroscopic measurements techniques:- 1) Point mechanics 2) Arbitrary reference frames Eg: Roentgenographic Cephalograms Only method specific descriptions, No structural detail. Constraint was removed by the continuum mechanics techniques of finite element method. Quantitative aspects of localized cephalic growth kinematics. 19 Moss ML. The functional matrix hypothesis revisited, 1.The role of mechanotransduction. Am J Orthod Dentofac Orthop 1997;112:8-11
  • 20. HIERARCHIAL CONSTRAINT 1) Did not extend - downwards or upwards. 2) Could not describe how extrinsic epigenetic FM stimuli are transduced into regulatory signals by individual bone cells. 3) Bone adaptation by - unicellular, unimolecular, or epigenomic levels. 20 Moss ML. The functional matrix hypothesis revisited, 1.The role of mechanotransduction. Am J Orthod Dentofac Orthop 1997;112:8-11
  • 21. 21 Genome Organ The Functional Matrix Hypothesis : Revisited (1990s) Moss ML. The functional matrix hypothesis revisited, 1.The role of mechanotransduction. Am J Orthod Dentofac Orthop 1997;112:8-11
  • 22. HOW TO OVERCOME HIERARCHIAL CONSTRAINT Four Complementary concepts 22 Moss ML. The functional matrix hypothesis revisited, 1.The role of mechanotransduction. Am J Orthod Dentofac Orthop 1997;112:8-11
  • 23.  FUNCTIONAL MATRIX HYPOTHESIS REVISITED-1 THE ROLE OF MECHANOTRANSDUCTION 23 FUNTIONAL MATRIX HYPOTHESIS - Revisited Moss ML. The functional matrix hypothesis revisited, 1.The role of mechanotransduction. Am J Orthod Dentofac Orthop 1997;112:8-11
  • 24. MECHANOSENSING All vital cells are irritable and respond to alterations in their external environment. Mechanosensing - Enables a cell to sense and respond to extrinsic loadings by using two processes. MECHANORECEPTION MECHANOTRANSDUCTION 24 Moss ML. The functional matrix hypothesis revisited, 1.The role of mechanotransduction. Am J Orthod Dentofac Orthop 1997;112:8-11
  • 25. MECHANOTRANSDUCTION Extra-cellular Stimulus Stimulus is Energy TRANSMITTED TRANSFORMED/TRANSDUCED RECEPTOR CELL SIGNAL in Intracellular MECHANORECEPTION MECHANOTRANSDUCTION VITAL CELLS Irritable (External Environment) Mechanosensing Process Moss ML. The functional matrix hypothesis revisited, 1.The role of mechanotransduction. Am J Orthod Dentofac Orthop 1997;112:8-11
  • 26. OSSEOUS MECHANOTRANSDUCTION Triad of bone cell adaptation process occurs When appropriate stimulus exceeds threshold values Deform extracellular matrix and bone cells Static and dynamic loads continuously applied to bone tissues Multiscale modeling of bone tissue mechanobiology, Bone 151 (2021) 116032 26 Load Moss ML. The functional matrix hypothesis revisited, 1.The role of mechanotransduction. Am J Orthod Dentofac Orthop 1997;112:8-11
  • 27. Intracellular stimulus reception Intercellular signal transmission Transduction Osteoblasts Directly regulate bone deposition and maintenance Osteoblasts Indirectly regulate osteoclastic resorption Triad of Bone cell Adaptation OSSEOUS MECHANOTRANSDUCTION 27 Moss ML. The functional matrix hypothesis revisited, 1.The role of mechanotransduction. Am J Orthod Dentofac Orthop 1997;112:8-11 RANKL RANK
  • 28. OSSEOUS MECHANOTRANSDUCTION - Osseous mechanotransduction is unique in four ways: 28 1) bone cells are not - cytologically specialized 2) Stimulus can evoke - three adaptational Responses 3) Osseous signal transmission is aneural. 4) Adaptational responses "bone organ" independently. Moss ML. The functional matrix hypothesis revisited, 1.The role of mechanotransduction. Am J Orthod Dentofac Orthop 1997;112:8-11
  • 29. 29 Moss ML. The functional matrix hypothesis revisited, 1.The role of mechanotransduction. Am J Orthod Dentofac Orthop 1997;112:8-11 Flow chart of FMH
  • 30. Types of mechanotransductive processes 30 1. Ionic – 2. Stretch activated channels – 3. Electrical processes - 4. Mechanical process - - Translate the information - periosteal functional matrix stimulus into skeletal cell signal. Moss ML. The functional matrix hypothesis revisited, 1.The role of mechanotransduction. Am J Orthod Dentofac Orthop 1997;112:8-11
  • 31. STRETCH ACTIVATED CHANNELS Deformation in strained bone tissue Plasma stretch activated ion channels Permit passage of certain ions- K+,Ca++,Na++ Ionic flow in turn initiates intracellular electrical events 31 Moss ML. The functional matrix hypothesis revisited, 1.The role of mechanotransduction. Am J Orthod Dentofac Orthop 1997;112:8-11 Extracellular matrix
  • 32. ELECTRICAL PROCESS : 1) ELECTROMECHANICAL voltage-activated ion channels. Transmembrane ionic flow Osseous transductive process. Ionic flows generate osteocytic action potentials. 32 Moss ML. The functional matrix hypothesis revisited, 1.The role of mechanotransduction. Am J Orthod Dentofac Orthop 1997;112:8-11
  • 33. ELECTRICAL PROCESS : ELECTROKINETIC  Bond and unbound electrical charges  Streaming potential (SP) origin. Conservation of electrical charges in deformed bone. SGP of ±2 mV can initiate osteogenesis and osteocytic action potentials. 33 Moss ML. The functional matrix hypothesis revisited, 1.The role of mechanotransduction. Am J Orthod Dentofac Orthop 1997;112:8-11
  • 34. ELECTRICAL PROCESS : ELECTRIC FIELD STRENGTH Extrinsic parameters are unclear. A significant parallel exists between the exogenous and endogenous field’s parameters. Bone responds to exogenous electric fields in an effective range of 1 to 10 µV/cm. 34 Moss ML. The functional matrix hypothesis revisited, 1.The role of mechanotransduction. Am J Orthod Dentofac Orthop 1997;112:8-11
  • 35. MECHANICAL PROCESSES  Hierarchically lower level bone cell genomic function.  Strain/deformation in the extra cellular bone matrix - transmitted Intracellularly via Mechanical levers. 35 Moss ML. The functional matrix hypothesis revisited, 1.The role of mechanotransduction. Am J Orthod Dentofac Orthop 1997;112:8-11
  • 36. FUNCTIONAL MATRIX HYPOTHESIS REVISITED-2 (THE ROLE OF OSSEOUS CONNECTED CELLULAR NETWORK) • Bone cells to carry out - mechano-sensation and transduction. Moss ML. The functional matrix hypothesis revisited, 2.The role of an osseous connected cellular network.Am J Orthod Dentofac Orthop 1997 36
  • 37. GAP JUNCTIONS Role of osseous connected cellular network(CCN) 37 Moss ML. The functional matrix hypothesis revisited, 2.The role of an osseous connected cellular network.Am J Orthod Dentofac Orthop 1997
  • 38. BONE AS AN OSSEOUS CCN • In the Network theory; Cells are arranged in 3 layers :- 1) Initial input layer 2) Intermediate / Hidden layer 3) Final output layer 38 Moss ML. The functional matrix hypothesis revisited, 2.The role of an osseous connected cellular network.Am J Orthod Dentofac Orthop 1997
  • 39. PROCESS OF NETWORK THEORY Loadings within each cell independently Cells in INITIAL layer receive several stimuli (weighted input) All stimuli (weighted inputs) are summed up If the value is greater than threshold value An intracellular signal is generated/ Mechanotransduction occurs 39 INITIAL INPUT Moss ML. The functional matrix hypothesis revisited, 2.The role of an osseous connected cellular network.Am J Orthod Dentofac Orthop 1997
  • 40. PROCESS OF NETWORK THEORY HIDDEN LAYER Signal transmitted by gap junctions to HIDDEN LAYER cells (adjacent osteocytes) Similar process of stimuli (weighted signal) summation, comparison, transmission occur Signal reaches Osteoblasts 40 Moss ML. The functional matrix hypothesis revisited, 2.The role of an osseous connected cellular network.Am J Orthod Dentofac Orthop 1997
  • 41. PROCESS OF NETWORK THEORY FINAL OUTPUT Osteoblasts reach the final layer Outputs of these anatomically superficial cells determines the Site, rate, direction, magnitude, duration of the specific adaptive response, i.e. deposition, resorption, and/or maintenance, of each cohort of osteoblasts. 41 Moss ML. The functional matrix hypothesis revisited, 2.The role of an osseous connected cellular network.Am J Orthod Dentofac Orthop 1997
  • 42. Attributes of CCN 42 1) Developmentally - 2) Operationally – 3) Structurally - Moss ML. The functional matrix hypothesis revisited, 2.The role of an osseous connected cellular network.Am J Orthod Dentofac Orthop 1997
  • 43. FUNCTIONAL MATRIX HYPOTHESIS REVISITED-3 (THE GENOMIC THESIS) • The initial version of FMH - was based on macroscopic experimental level. 43 The functional matrix hypothesis revisited. 3. The genomic thesis,Am J Orthod Dentofacial Orthop, 1997 Sep;112(3):338- 42. Recent version – hierarchically upward, microscopic level and mechanism of gene expression.
  • 44. The genomic thesis Initial regulatory (homeobox) gene activity 44 The functional matrix hypothesis revisited. 3. The genomic thesis,Am J Orthod Dentofacial Orthop, 1997 Sep;112(3):338-42. • In orofacial biology , Prenatal craniofacial development is controlled by two process :- • DNA - from the moment of fertilization all the information necessary for the regulation • It includes regulation of intranuclear formation and transcription of mRNA. • It is the genome of an individual which determines the overall phenotype. Subsequent activity of the regulatory molecular groups
  • 45. 45 The Biology primer – Jason Walker
  • 46. FUNCTIONAL MATRIX HYPOTHESIS REVISITED-4 (The epigenetic antithesis and the resolving synthesis) 46 The functional matrix hypothesis revisited. 4. The epigenetic antithesis and the resolving synthesis, Am J Orthod Dentofacial Orthop, 1997 Oct;112(4):410-7.
  • 47. THE EPIGENETIC ANTITHESIS • It refers to the entire series of interaction among cells and cell products which lead to morphogenesis and differentiation. Process :- Mechanism :- 47 The functional matrix hypothesis revisited. 4. The epigenetic antithesis and the resolving synthesis, Am J Orthod Dentofacial Orthop, 1997 Oct;112(4):410-7.
  • 48. Epigenetic process of loading • Many different mechanism are capable of modifying phenotype. 1) Loads may act at – Cellular and Tissue level 2) Loads may be – Dynamic and Static 3) To be effective load may increase, decrease or remain constant. 48 The functional matrix hypothesis revisited. 4. The epigenetic antithesis and the resolving synthesis, Am J Orthod Dentofacial Orthop, 1997 Oct;112(4):410-7.
  • 49. A RESOLVING SYNTHESIS Morphogenesis Genomic factors Intrinsic Prior Causes Epigenetic factors Extrinsic Proximate Causes 49 It provides the necessary and sufficient causes of growth and development The functional matrix hypothesis revisited. 4. The epigenetic antithesis and the resolving synthesis, Am J Orthod Dentofacial Orthop, 1997 Oct;112(4):410-7.
  • 50. CLASSICAL CATEGORISATION OF CAUSATION • There are four principles causes of ontogenesis :- Material :- (What is act upon?) Formal :- ( Set of rules?) Efficient :- (Immediate preceding event?) Final :- ( Why?) 50 The functional matrix hypothesis revisited. 3. The genomic thesis,Am J Orthod Dentofacial Orthop, 1997 Sep;112(3):338-42.
  • 52. REFFERENCES • Textbook of Craniofacial Growth – Sridhar Premkumar 1St edition. • Orthodontics – The Art and Science - 5th Edition – S. I. Bhalajhi • The differential roles of periosteal and capsular functional matrices in orofacial growth – Melvin L. Moss – European Journal Of Orthodontics, Volume 29 – April 2007 • Multiscale modeling of bone tissue mechanobiology, Bone 151 (2021) 116032 • Moss ML. The functional matrix hypothesis revisited, 1.The role of mechanotransduction. Am J Orthod Dentofac Orthop 1997;112:8-11 • Moss ML. The functional matrix hypothesis revisited, 1.The role of mechanotransduction. Am J Orthod Dentofac Orthop 1997;112:8-11 • Moss ML. The functional matrix hypothesis revisited. 3. The genomic thesis, Am J Orthop Dentofacial Orthop, 1997 Sep;112(3):338-42 • Moss ML. The functional matrix hypothesis revisited. 4. The epigenetic antithesis and the resolving synthesis, Am J Orthod Dentofacial Orthop, 1997 Oct;112(4):410-7. 52