Functional matrix theory revisited/ dental implant courses by Indian dental academy

FUNCTIONAL MATRIX THEORY

INDIAN DENTAL ACADEMY Leader in continuing dental education www.indiandentalacademy.com www.indiandentalacademy.com

Contents:        

1. Introduction 2. Origin of work 3. Statement of Hypothesis 4. Functional cranial analysis 5. Clinical application of FMH 6. Support 7. Against 8. Constraints of FMH www.indiandentalacademy.com

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9. FHM-1. The role of mechanotransduction 10. FHM-2. The role of osseous connected cellular network 11. FHM-3. The genomic thesis 12. FHM-4. The epigenetic antithesis and the resolving synthesis.

13. Conclusion 14. References www.indiandentalacademy.com

INTRODUCTION: 

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Melvin L. Moss introduced the concept of functional matrix to the dental profession in the year 1962 in a chapter of that title in vistas of orthodontics [B. Kraus and R.Riedel}.

In the intervening 35 yrs, the FMH has gained broad acceptance, even meriting an entry in current edition of Dorland’s Medical Dictionary. www.indiandentalacademy.com

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Melvin has often admitted that he probably would not have selected the term “functional matrix” as a description of his work, which he preferred to call functional cranial analysis.

The term “functional matrix” was chosen as a title for the 1962 chapter under deadline pressure for manuscript submission.

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Origins of the work: ď Ź

As in the case in most scientific endeavors, the discovery did not occur in a single moment, it was a combination of factors – all determining the development of the body of work now known as the functional matrix hypothesis.

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In a summary of his own early work, Mel described the process of scientific investigation as follows. “ There is a cyclic process at work which alternates between periods of hypothesis and insight, followed by periods of intensive investigations, and ending in a time of synthesis” (Moss,1972) www.indiandentalacademy.com

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Based on the original concepts of Dutch Zoologist Van der Klaauw(1948-1952) who has introduced the concepts of functional cranial components.

Others investigators- James H.Scott and Sherwood washburn- independently published similar functional analyses in this period influenced Moss. www.indiandentalacademy.com

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Two seminar books – “On Growth and form” D’Arcy Wentworth Thompson’s and “The Development of Vertebral Skull” by Gavin De Beer – played an important role in the direction of Mel’s early experimental work.

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His thesis research demonstrates that the extripation of calvaria sutures in a growing animal produced no dimensional decrease of the neural skull.

This lead to the conclusion that sutural tissues are not primary growth centers that act to ‘push” bones apart (Moss, 1954)

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It was readily apparent to Mel that the growth of the neurocranium was a response to the primary growth of the neural mass and that the sutures were sites of secondary, compensatory skeletal responses to that growth.

This hypothesis was experimentally tested and verified in Mel’s lab and subsequently in many others throughout the world. www.indiandentalacademy.com

STATEMENT OF HYPOTHESIS:

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The FMH claims that the origin, form, position, growth and maintenance of all skeletal tissues and organs are always secondary, compensatory and necessary responses to chronologically and morphologically prior events or process that occur in specifically related non-skeletal tissues, organs or functional spaces.

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Functional cranial analysis: Functional Components & Skeletal units 

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According to Moss, the head is a structure designed to carryout functions, e.g. neural integration, respiration, digestion, hearing, olfaction & speech.

Each of these functions is accomplished by certain tissues & spaces in the head. The tissues and spaces responsible for a single function have been termed a functional cranial component.

Each component consists of all of the tissues, organs, spaces and skeletal parts necessary to carryout a given function completely. www.indiandentalacademy.com

Functional Cranial Component One function

Skeletal tissue

Neural tissue

Muscle tissue

Vascular tissue

Functional Cranial Component www.indiandentalacademy.com

Functional Cranial Component

Tissues and spaces that completely perform a function

Functional matrix

A related skeletal unit that acts biomechanically to protect and/or support its functional matrix Skeletal cranial component

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SKELETAL UNITS: 

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Skeletal units may be composed of bone, cartilage, or tendinous tissues. They are not the equivalents of the bones of formal, classic osteology.

Moss divided the skeletal units into, Microskeletal units Macroskeletal units www.indiandentalacademy.com

Microskeletal units: 

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When a ‘bone’ of formal, classic osteology consists of a number of skeletal units, we call them microskeletal units.

That is, both the maxilla and the mandible are formed of a number of such contiguous microskeletal units.

Microskeletal units are influenced by periosteal functional matrices. www.indiandentalacademy.com

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In the mandible, coronoid microskeletal unit is related to the functional demands of the temporalis muscle, an angular microskeletal unit is related to the activity of both the masseter and medial pterygoid muscles, alveolar unit is related to the presence and position of teeth and the basal microskeletal unit is related to the inferior alveolar neurovascular triad matrix.

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To a variable extent, contiguous microskeletal units are independent of each other. This implies that changes in the size, shape or position of the coronoid process as a result of primary changes in temporalis muscle are relatively independent of such changes in other mandibular microskeletal units. www.indiandentalacademy.com

Macroskeletal unit: ď Ź

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When adjoining portions of a number of neighboring bones united to function as a single cranial component, we term this a macroskeletal unit.

The endocranial surface of the calvaria is an example. The neural mass within its capsules elicits a reaction on the surface of the calvarium.

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As a result, apposition on the occipital, parietal, temporal & frontal bones occurs as if all of them were but one bone. This sharing of reaction by several adjacent bones constitutes a macroskeletal unit.

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Functional Matrix: ď Ź

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Functional matrices provide the extrinsic (environmental) influences, which are morphogenetically primary for the form, growth, position and maintenance in being of all skeletal units.

For example the size and shape of the angular and coronoid mandibular processes are secondary and compensatory, to primary changes in the functional demands of the masseter, medial pterygoid and temporalis www.indiandentalacademy.com muscle respectively.

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There are two distinct types of functional matrix.

The periosteal matrix The capsular matrix.

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Periosteal Functional Matrix:  

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The first type of functional matrix has been named periosteal.

This term relates the matrix to those tissues that influence the bone directly through the periosteum.

Muscles are attached to the periosteum and consequently are excellent examples of this kind of matrix.

Blood vessels & nerves lying in grooves or entering or exiting through foramen can also exert a periosteal influence on the skeletal unit www.indiandentalacademy.com

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The periosteal matrix affects a microskeletal unit meaning that the sphere of influences is usually limited to a part of one bone.

E.g. (1) Temporalis muscle exerts most of its action on the coronoid process, a microskeletal unit of the mandible.

(2). A tooth is responsible for the alveolar bone that supports its, extract the tooth (the periosteal functional matrix) and the microskeletal unit (the immediate alveolar process) disappears. www.indiandentalacademy.com

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Capsular Functional Matrix: 

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This is the second type of functional matrix.

Included in this class of matrix are those masses and spaces that are surrounded by capsules.

All functional cranial components (skeletal units plus functional matrices) arise, grow, operate and are maintained within a series of cranial capsules.

For instance, the neural mass is contained within a capsule of scalp, duramater etc and the orbital mass is surrounded by the supporting tissues of the eye. www.indiandentalacademy.com

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The oral-nasal-pharyngeal spaces are surrounded by a variety of tissues that compose their capsules.

Each of these capsules is an envelope, which contains a series of functional cranial components (skeletal units plus their related functional matrices), which as a whole, are sandwiched in between two covering layers. www.indiandentalacademy.com

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In the neurocranial capsule these covers consist of the skin and the duramater, whereas in the orofacial capsule the skin and mucosa form these limiting layers.

Capsular functional matrices differ completely in their action. These capsules tend to influence macroskeletal units, which means that portions of several bones are simultaneously affected.

E.g. The inner surface of calvarium. www.indiandentalacademy.com

Neuro cranial capsule:

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In the neurocranium, the primary growth force in derived from the volumetric expansion of the enclosed neural mass (brain, meninges, cerebrospinal fluid) the neurocranial capsule expands secondarily in response to this increase in functional matrix volume. Accordingly the developing calvarial bones are passively carried upwards & outwards within their enclosing capsule.

As the neural mass enlarges, the bones within the capsule are displaced outward in a process termed translation. The sutures are not separating the bones by the pressure of cell proliferation; instead, they are preventing the creation of voids by filling in the separating areas. Thus, a functional matrix influences a macroskeletal unit the entire cranium. www.indiandentalacademy.com

Oro-facial capsule:

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ORO FACIAL MATRICES ď Ź

All functional cranial component of the facial skull arise, grow and are maintained with in the oro facial capsule. This capsule surrounds & protects the oro-nasopharyngeal functioning spaces.It is the volumetric growth of these spaces which is the primary morphogenetic event in facial skull growth

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While the primitive palate is formed when the maxillary and nasal processes join, most of the primitive oronasal functioning space remains a common volume.

It is only when the bilateral palatal processes form (at about the 40 day), elevate, and fuse (47 to 50 day) that the functional differentiation between the oral and nasal functioning spaces occurs. www.indiandentalacademy.com

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According to moss the mandibular condylar cartilage is not a primary site of mandibular growth. They are loci at which secondary, compensatory periosteal growth occurs.

The downward and forward relocation of the contiguous mandibular skeletal units as a whole occurs as a response to the primary volumetric increase of the oral, nasal and pharyngeal cavities. The oro-facial capsule expands and carries the completely embedded mandible in the www.indiandentalacademy.com direction of these growth vectors.

CLINICAL APPLICATIONS OF FUNCTIONAL MATRIX HYPOTHESIS        

1.Orthodontic tooth movement (periosteal matrix) – alveolar bone transformation( micro skeletal unit) 2.Orofacial orthopedics (capsular matrix) – jaw bones (macro skeletal unit) 3.Widening of midpalatal sutures (RPE) 4.Repositioning of maxillary segments in cleft cases 5.Inclined bite planes 6.Functional appliance therapy 7.Bilateral condylectomy 8.Distraction osteogenesis www.indiandentalacademy.com

Support    

Microcephaly Hydrocephaly The relation between the eye and the size of the orbit It is noted in 20 to 25% of children in whom a growth deficit occur after condylar fracture.

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Mandibular ankylosis caused by severe infection in the area of TMJ, leading to destruction of tissue and ultimate scaring.

Diminution in the size of the coronoid process subsequent to experimental denervation of the temporalis muscle.

Shinkage of alveolar process Spatial maintenance of the appropriate foramina in response to the demand for an unloaded neural pathway www.indiandentalacademy.com

Against The theory does not make it clear how the functional needs are transmitted to the tissues Craniostenosis – premature stenosis of sutures inhibits growth – sutures have some capacity to regulate the activity of functional matrix In 75 to 80% of the children who suffer a condylar #, the resulting loss of condyle does not impede mandibular growth www.indiandentalacademy.com

CONSTRAINTS OF FUNCTIONAL MATRIX HYPOTHESIS:      

1.METHODOLOGIC: -Cannot structurally detail the measurements done using cephalograms.

Removed by FEM analysis 2. HIERARCHICAL: Does not describe processes in cellular\ subcellular\ molecular structural domains Does not describe how bone responds to www.indiandentalacademy.com lower level signals

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Does not describe either how individual cells communicate to produce coordinated multicellular responses.

Accordingly, their results and derivative hypotheses generally are not extensible to higher multicellular, tissue, levels.

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At present, no unitary hypothesis provides a comprehensive, coherent and integrated description of all the processes and mechanisms involved in bone growth, remodeling, adaptation, and maintenance at all structural levels.

This newest FMH version, presented herein, transcends some hierarchical constraints and permits seamless descriptions at, and between, the several levels of bone structure and operation-from the genomic to the organ level. www.indiandentalacademy.com

FUNCTIONAL MATRIX REVISITED (MOSS 1997)   

It does so by the inclusion of two complementary concepts: (1) that mechanotransduction occurs in single bone cells, and (2) that bone cells are computational elements that function multicellularly as a connected cellular network.

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. Further, a physical chain of macromolecular levers, connecting the extracellular matrix to the bone cell genome is described, suggesting another means of epigenetic regulation of the bone cell genome, including its phenotypic expression. (Am J Orthod Dentofac Orthop 1997;112:8-11.)

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These articles include the molecular & cellular processes underlying the triad of active skeletal growth processes1. Deposition 2. Resorption 3. Maintenance

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Basic terminologies ď Ź

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COHORT- large group of homologous osteoblasts, concerned with a single function.

There is a sharp demarcation between adjacent cohorts of active\ depository\ quiescent osteoblasts.

HIERARCHY- Structural & functional complexity increasing upward from subatomic particles to tissues to organs. www.indiandentalacademy.com

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EMERGENCE- appearance of new attributes\ properties in each successively higher level.

Due to the integrated activities of all the attributes in a given hierarchical level to selforganize to produce next higher level of complexity CAUSATION- How the attributes of a given biologic structural level control, regulate& determine the attributes of next higher level. www.indiandentalacademy.com

FUNCTIONAL MATRIX REVISITED1

(MOSS :july,1997)

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MECHANOTRANSDUCTION:    

All Vital cells- irritable & respond to alterations in the environment.

This response is via. Mechanosensing processes 1. Mechanoreception- transmits extra cellular stimulus into the cell.

2. Mechanotransduction- transforms the stimulus’ informational content into intracellular signal

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Mechanotransduction is one type of cellular signal transduction. There are several mechanotransductive processes, for example, a)mechanoelectrical b)mechanochemical.

Whichever are used, bone adaptation requires the subsequent intercellular transmission of the transduced signals. www.indiandentalacademy.com

Osseous mechanotransduction  

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Any loading (static\ dynamic)- deform extra cellular matrix & bone cells- stimulus If exceeds threshold value- the loaded tissue responds by the triad of bone cell adaptation processes.

Both osteocytes and osteoblasts are competent for intracellular stimulus reception and transduction and for subsequent intercellular signal transmission. www.indiandentalacademy.com

Osteoblasts

directly regulate bone deposition and maintenance and indirectly regulate osteoclastic resorption

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Uniqueness of osseous transduction: 1. Bone cells are not cytologically specialized 2. One stimulus can cause triad of response 3. Aneural signal transmission 4. Response confined within the individual bone

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Mechonotransduction can be –  1. Ionic\electrical  2. Mechanical 

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Ionic or electrical processes. ď Ź

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This involves some process(es) of ionic transport through the bone cell (osteocytic) plasma membrane.

There is a subsequent intercellular transmission of the created ionic or electrical signals that, in turn, are computed by the operation of an osseous connected cellular network.

That network's output regulates the multicellular bone cell responses www.indiandentalacademy.com

Stretch-activated channels. ď Ź

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One of these involves the plasma membrane stretch-activated (S-A) ion channels, a structure found in bone cells.

When activated in strained osteocytes, they permit passage of a certain sized ion or set of ions, including K+, Ca2+,& Na+.

Such ionic flow may, in turn, initiate intracellular electrical events, for example, bone cell S-A channels may modulate membrane potential as well as Ca2+ ion flux. www.indiandentalacademy.com

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Electrical processes. ď Ź

These include several, nonexclusive mechanotransductive processes (e.g., electromechanical and electrokinetic), involving the plasma membrane and extracellular fluids.

Electric field strength may also be a significant parameter.

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1. Electromechanical. As in most cells, the osteocytic plasma membrane contains voltage-activated ion channels, and transmembrane ion flow may be a significant osseous mechanotransductive process. ionic flow thru ion channels generate osteocytic action potential capable of transmission to other bone cells through gap junctions www.indiandentalacademy.com

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2. Electrokinetic. It is generally agreed that electrical effects in fluid-filled bone are not piezoelectric, but rather of electrokinetic, that is, streaming potential (SP) origin.

The SP is a measure of the strain-generated potential (SGP) of convected electric charges in the fluid flow of deformed bone.

The usually observed SPG of ±2 mV can initiate both osteogenesis and osteocytic action potentials. www.indiandentalacademy.com

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3. Electric field strength. Bone responds to exogenous electrical fields. Although the extrinsic electrical parameter is unclear, field strength may play an important role.

A significant parallel exists between the parameters of these exogenous electrical fields produced by muscles and the endogenous fields produced by bone Bone responds to exogenous electrical fields in an effective range of 1 to 10 µV/cm www.indiandentalacademy.com

MECHANICAL PROCESSES 

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Strain\ deformation in the extra cellular bone matrix- transmitted intracellularly via.

Mechanical levers.

INTEGRIN- connected extracellularly with matrix collagen & intracellularly with cytoskeletal actin.

ACTIN- connected to nuclear membrane.

ACTIVATION OF NUCLEAR MEMBRANEinitiates series of intracellular processes regulating genomic activity.

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Mechonotransduction can be – 1. Ionic\electrical 2. Mechanical

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It is thus suggested that such a cytoskeletal lever chain, connecting to the nuclear membrane, can provide a physical stimulus able to activate the osteocytic genome, possibly by first stimulating the activity of such components as the cfos genes.

It is by such an interconnected physical chain of molecular levers that periosteal functional matrix activity may regulate the genomic activity of its strained skeletal unit bone cells, including their phenotypic expression. www.indiandentalacademy.com

FUNCTIONAL MATRIX REVISITED2

(MOSS :aug,1997)

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THE ROLE OF AN OSSEOUS CONNECTED CELLULAR NETWORK

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All bone cells except osteoclasts, are extensively inter connected by gap junctions that form an osseous CCN

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GAP JUNCTIONS: 

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Each bone cell has numerous cytoplasmic processes which lie within the mineralized bone matrix ( canaliculi) Gap junctions are found where plasma membranes of 2 cytoplasmic processes meet.

Connect superficial osteocytes to the periosteal & endosteal osteoblasts Connect periosteal osteoblasts to pre osteoblasts All these cells form the CCN. www.indiandentalacademy.com

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Functions of gap junctions: 

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Mechanotransductively activated bone cellsinitiate membrane potential- ionic signals – transmitted via gap junctions Permit bi directional signal traffic Open gap junctions- interconnect osteoblasts of similar cohort( engaged in identical adaptational process) Close gap junctions- histologic discontinuities between phenotypically different osteoblasts. www.indiandentalacademy.com

GAP JUNCTION

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Connectionist\ Network theory:    

Bone cells are organised into 3 layers: 1. Initial input layer 2. Final output layer 3. Intemediate\Hidden layer

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1. Initial layer cells:

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Receive loadings (weighted inputs\ “stimuli”) Within each cell, the weighted inputs are summed & compared with a liminal\ threshold value If it exceeds threshold value, intracellular “signal” is generated Transmitted to intermediate osteocytes via gap junctions

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2. Hidden layer:

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Summation, comparison & transmission occurs “ Signal” reaches the final layer of osteoblasts

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3. Final layer:

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Similar processes repeat Final “output” determines the site, rate, direction, magnitude & duration of the final specific “RESPONSE”- deposition\ resorption\ maintenance.

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Functions of CCN: ď Ź ď Ź ď Ź

1. Act as an artificial neural network with parallel distribution of signal 2. Processes the intracellular stimuli via a multiprocessor network mode 3. Output signals from CCN move hierarchically upward to regulate skeletal unit adaptational processes via osteoblasts.

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A skeletal CCN displays the following attributes ď Ź

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Developmentally, it is an untrained selforganised &self-adapting and epigenetically regulated system.

Operationally,it is a stable, dyanamic system that exhibits oscillatory behavior permitting feedback Structurally, an osseous CCN is non modular i.e. permits discrete processing of differential signals. www.indiandentalacademy.com

CONCLUSION ď Ź

The addition to the FMH of the concepts of mechanotransduction and of computational bone biology offers an explanatory chain through the cellular and molecular levels to the bone cell genome.

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FUNCTIONAL MATRIX REVISITED3 (MOSS :Sept,AJO- DO, 1997)

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The epigenetic/genomic problem is a dichotomy, and dialectics is one analytical method for its resolution. The method consists of the presentation of two opposing views, a thesis and an antithesis, and of a resolving synthesis.

Such a dialectic analysis is presented here in two interrelated articles that respectively consider (1) the genomic thesis and (2) an epigenetic antithesis and a resolving synthesis. www.indiandentalacademy.com

THE GENOMIC THESIS: ď Ź

According to this theory the whole series of operations to be carried out, the order and site of synthesis and their co-ordination are all written down in the nucleic acid

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This thesis holds that from the moment of fertilization the genome contains all information necessary to regulate – 1. The intra nuclear formation &transcription of RNA .

2.With out any external factor regulate intracellular &intercellular activities of cell tissues and organs & all phenotypic features are expressed by DNA www.indiandentalacademy.com

The Biologic Bases for the 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.

The human genome has approximately 100,000 genes, Only approximately 10% of the genome seems related to phenotypic ontogenesis, "well over 90% . . . does not encode precursors to mRNAs or any other RNA.“ www.indiandentalacademy.com

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All somatic cells commonly share approximately 5000 different polypeptide chains, but each specific cell type is characterized only by approximately 100 specific proteins.

And it claimes that "these quantitative (protein) differences are related to differences in cell size, shape and internal architecture." www.indiandentalacademy.com

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The encoding 10% of the DNA exists in two families; 1."housekeeping" genes and 2. "structural" genes.

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1.Housekeeping" genes regulate the

normal molecular synthesis of agents involved in (1) the common energetic (metabolic, respiratory) activities of all cells and, (2) the specific activities of special cell types (e.g., neurons, osteoblasts, ameloblasts etc.). www.indiandentalacademy.com

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2.Structural genes

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These genes regulate the synthesis of the specific molecular gene products The presence, absence, or abnormal molecular configuration of these genes is associated with the pathologic conditions with a unitary genetic cause (Mendelian disorders \ single-gene disorders)

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Genomic thesis for orofacial growth 

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A charecteristic article claims that prenatal craniofacial development is controlled by two interrelated, temporally sequential, processes: (1) initial regulatory (homeobox) gene activity, followed by (2) regulatory molecular groups: Growth factor families Steroid/thyroid/retinoic acid super-family www.indiandentalacademy.com

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Homeobox genes: Coordinate the development of complex craniofacial structures Much of the regulation of the development of the skeletal and connective tissue of the face is dependent on a cascade of overlapping activity of homeobox genes

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Regulatory molecules: Alter the manner in which homeobox genes coordinate cell migration and subsequent cell interactions that regulate growth Are involved in the "genetic variations contributing to the abnormal development of relatively common craniofacial malformations (modify Hox gene activity). www.indiandentalacademy.com

Orthodontic implications of genomic thesis ď Ź

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Poorly coordinated control of form and size of structures, or groups of structures (e.g., teeth and jaws) by regulator genes explain the mismatches found in malocclusions and other dentofacial deformities."

Single Homeobox gene can control the development of complex structures indicating that single genes can determine the morphology of complex structures, as the inheritance of jaw www.indiandentalacademy.com patterns"

FUNCTIONAL MATRIX REVISITED4 (MOSS :OCT,AJO- DO, 1997)

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EPIGENETIC ANTITHESIS  

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Strengths against genomic thesis 1.Gene is a unit of heredity(DNA sequences incorporate information needed for the generation of a RNA) 2.Genetic machinery is a kind of information which DNA\RNA molecules are inherently capable of containing- nothing about which proteins will be expressed in which cells at what time and in what quantities www.indiandentalacademy.com

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3.Genomic theory- reductionist & molecular Morphogenetic processes are reduced to explanations of mechanisms at the molecular (DNA) level.

Ex- the genomic thesis of craniofacial ontogenesis -passes directly from molecules (DNA) to morphogenesis(adult morphology), ignoring the role of epigenetic processes and mechanisms www.indiandentalacademy.com

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4.epigeneic antithesis is a. Integrative- clarifies the causal chain between genome and phenotype. b. Goal - identifies and describes comprehensively the series of initiating biological processes and their related underlying (biochemical, biophysical) responsive mechanisms www.indiandentalacademy.com

WHAT IS EPIGENETICS ď Ź

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Refers to the entire series of interactions among cells and cell products which leads to morphogenesis and differentiation.

Thus all cranial development is epigenetic by definition

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Epigenetic factors include – 1. All extrinsic, extraorganismal, macroenvironmental factors impinging on vital structures (for example, food, light, temperature), including mechanical loadings and electromagnetic fields, 2. All intrinsic, intraorganismal, biophysical, biomechanical, biochemical, and bioelectric microenvironmental events occuring on, in, and between individual cells, extracellular materials, and cells and extracellular substances. www.indiandentalacademy.com

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In terms of clinical orthodontics, and of the FMH, all therapy is applied epigenetics, and all appliances (and most other therapies) act as prosthetic functional matrices.

Clinical therapeutics includes a number of epigenetic processes, whose prior operations evoke a number of corresponding epigenetic mechanisms. www.indiandentalacademy.com

EPIGENETIC PROCESS AND MECHANISM:     

1.LOADING 2.EXTRA CELLULAR MATRIX DEFORMATION 3.CELL-SHAPE CHANGES: 4.EPIGENETIC CELL SIGNALLING PROCESSES. 5.CHAINS OF INTRACELLULAR MOLECULAR LEVERS: www.indiandentalacademy.com

1. Loading  

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Loads may be imposed at many structural levels.

While clinical observations usually are macroscopic, the loadings act microscopically, at molecular and/or cellular levels.

Loadings are able to regulate several alternative molecular (cellular) synthetic pathways of many tissues, including bone ex: the mechanical environment is important in maintaining the differentiated phenotype of bone cells. www.indiandentalacademy.com

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Mechanical loading is known to influence gene expression.

Of clinical (and FMH) interest, extrinsic musculoskeletal loading can rapidly change (1) both articular cartilage intercellular molecular syntheses and mineralization and (2) osteoblastic (skeletal unit) gene expression. www.indiandentalacademy.com

2. EXTRA CELLULAR MATRIX DEFORMATION:  

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Musculoskeletal tissue loading deforms ECM. ECM regulates the formation, development, and maintenance of its included cells that synthesize the ECM. Further, ECM can regulate multicellular tissue morphogenesis and contribute to genomic regulation of its enclosed cells.

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3. CELL-SHAPE CHANGES: ď Ź

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Tissue loading alter cell shape- deforms intracellular constitutents, including the cytoskeleton.

The epigenetic process of changing cell shape invokes the epigenetic mechanisms of mechanotransduction of biophysical forces into genomic and morphogenetically regulatory signals. www.indiandentalacademy.com

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Cell-shape change processes activate stretch-activated ion channels in cartilage and other mechanically initiated cell-signaling mechanisms.

Cell-shape change lead to nuclear shape deformation- can directly cause a consequent alteration of the mechanisms of genomic activity www.indiandentalacademy.com

4. EPIGENETIC CELL SIGNALLING PROCESSES. ď Ź ď Ź

Several loading processes regulate genomic expression. one, previosly described, begins with Cellular mechanoreception and mechanotransduction of the loading stimulus into an intercellular signal undergoes parallel processing within a connected cellular network of bone cells.

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5.CHAINS OF INTRACELLULAR MOLECULAR LEVERS: ď Ź

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Deformation of the ECM has an epigenetic regulatory role in morphogenesis, by virtue of integrin molecules that interconnect the several molecular components of the intracellular (cytoskeletal) and the extracellular environment .

The epigenetic mechanism evoked consists of a physical array of intracellular macromolecular chains, acting as levers, extending from the cell membrane to multiple specific sites on each www.indiandentalacademy.com chromosome.

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The molecular chain acts as an information transfer system between the extracellular environment and the genome, transmitting signals generated by deformations of the ECM directly to the intranuclear genome.

Such informational transfer between cells and ECM is dynamic, reciprocal, and continuous. www.indiandentalacademy.com

RESOLVING SYNTHESIS 

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It argues that morphogenesis is regulated (controlled, caused) by the activity of both genomic and epigenetic processes and mechanisms.

Their integrated activities provide the necessary and sufficient causes of growth and development.

Genomic factors are intrinsic and prior causes; Epigenetic factors are extrinsic and proximate causes. www.indiandentalacademy.com

CONCLUSION: ď Ź

There is no reason for conflict between the genomic and epigenetic hypotheses of ontogenetic regulation when it is perceived that they are interdependent, yet different, categories of necessary causes and that only their unity provides the sufficient condition for growth and development to occur.

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References:       

Melvin L. Moss and the functional matrix – letty MossSalentijn (J Dent Res 76(12) 1997) The primary role of fuctional matrices in facial growth (jun(20-31)1969) FMH revisited .1.(Moss ,AJO-DO, july 1997) FMH revisited .2.(Moss ,AJO-DO, aug 1997) FMH revisited .3.(Moss ,AJO-DO, sept 1997) FMH revisited .4.(Moss ,AJO-DO, oct 1997) CONTEMPORARY ORTHODONTICS- WILLIAM R. PROFFIT www.indiandentalacademy.com

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