GROWTH AND DEVELOPMENT – A Bird’s Eye View

This shall be divided into three parts for the sake of convenient:

a) Growth and development in general.

b) Factors affecting growth and development.

c) Theories of growth and development.

In the first part, titled

Growth and development in general, we shall look at the following aspects:

i) What is growth? What is development?

ii) Why do we need to study about growth development.

iii) Normal features of growth and development.

a. Differentiatial growth.

b. Pattern.

c. Variability.

d. Timing, rate and direction.

e. Normality.

iv) Mechanisms of growth in:

- Soft tissues.

- Hard tissues.

v) Evolution of the human head form.

vi) Measurement and prediction of growth.

vii) Clinical implications.

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What is growth? What is development? Though closely related growth and

development are not one and the same.

Definition of growth Growth :

- Growth usually refers to an increase in size – Profile (Todd).

- Growth may be defined as the normal change in amount of living

substance – Moyers.

Definition of development Development :

- Development connotes a maturational process involving progressive

differentiation at the cellular and tissue levels – Enlow.

- Development refers to all naturally occurring progressive, sequential and

unidirectional changes in the life of an individual from its existence as a

single cel to its elaboration as a multifunctional unit terminating in death –

Moyers.

- Development is a progress towards maturity (Todd).

- Morphogenesis : A biologic process having an underlying control at the

cellular and tissue levels – Enlow.

- As can be understood from the above definitions, growth and development

are complementary to each other.

- One can also draw certain correlations between growth and development.

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Co-relation between growth and development:

- Growth emphasizes the normal dimensional changes during development.

- Because growth is mainly anatomic; also quantitative.

Development growth + differentiation + translocation.

- Development is mainly physiologic and qualitative.

- Development implies an increased specialization wit a decrease in

function. Thus, it is the combination of growth and morphogenesis Self

Multiplication.

+ Differentiation.

+ Organization.

Individual phenotype.

Why do we need to study growth and development?

To have an understanding of the following:

a) Normal growth and how it occurs.

b) Patterns of abnormal growth and the reason(s).

c) To distinguish between normal and abnormal.

d) Utilize growth (“working with growth”) to our benefit.

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Normal Features of Growth and Development :

a) Differential growth – different tissues and in turn different organs grow at

different rates. This process is called differential growth. As depicted in

figure 1, in a normal individual, the neural tissues grow early in life

completing their maturation first, followed by the lymphoid tissues, which

actually diminish in size after puberty. The remaining general body fuses

mature later; the last being the genital tissues. The maxilla and the

mandible follow the general body growth; the mandible slightly slower

than the maxilla initially but catches up later.

It is important to know this because a male child who presently with a

slight mandibular deficiency at age 12 should be expected to have a normal

mandibular size by age 15-16 years.

b) Pattern of growth – pattern is a set of constraints, quantitative or geometric

rules, operating to preserve integration of parts under varying conditions or

through time.

These constraints may be in the form of coordinated transformations,

cybernetic mechanisms and compensations of various sorts.

What this essentially means is that growth demonstrates certain complex

proportionalities which change wit time. For example : At 3 months of

intrauterine life, the human foetus is almost 50% of the total body length.

This, for that particular time is normal. At birth, the trunk and limbs, which

were earlier rudimentary have grown faster than the head and therefore the

proportion of head size to the rest of body length is about 25-30%. Eventually,

at adulthood, the head size is just about 12% (Figure 2); these reflect the

complexity in proportions, which change with time.

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In relation to differential growth and indicative of a normal growth pattern, is

the cephalocaudal gradient of growth.

- Predictability of growth pattern : as can be inferred from figure 2, a

specific kind of proportionality exists at a particular time and progresses

towards another at the next time frame, with a slight variations.

- This has important implications : In prediction of the future growth pattern

(using growth charts for that population) and to recognize if the individual

has deviated from his original growth pattern.

- This particular gradient connotes the variance of growth between the

cephalic (head end) and the caudal (fail end i.e. limbs and extremities).

This can be amply inferred from figure 2.

- It is interesting that even within the craniofacial skeleton, there exists a

cephalocaudal gradient; The skull of an infant occupies almost 2/3rd –3/4 of

the cranial complex. The maxilla grows next and the mandible (being at

the caudal end) is the last to grow (Figure 3).

In orthodontic, pattern has a morphogenetic as well as a developmental

application.

- Morphogenetic – For ex: the statement he has a Class III facial pattern.

- Developmental – Mohan ha a vertical growth pattern.

- Patterns can be quantified in terms of craniofacial constants, which show

invariance.

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Implications of pattern:

- Analysis of morphology.

- Study of stability of treatment.

Variability : No two individuals, with the exception of monozygotic twins are

alike, i.e. variation is the law of nature.

To express variability quantitatively, it is useful to categorize in terms of

deviations from the usual pattern.

This is done using standard growth charts. The growth charts help in:

- Determining whether growth is normal or abnormal.

- To evaluate growth over a period of time.

- Growth charts are available for Indian population through the Indian

Council for medical research and Life Insurance Corporation.

Variability of growth may be seen in terms of:

a) Chronologic age – variation due to timing and because chronologic age is

not a good indicator of growth status.

b) Ethnic group.

c) Sexes.

d) Variance with time – secular trend.

e) Body type.

Normality : Normal refers to what is usually expected, seen or is typical.

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It is important to distinguish normal from the ideal – because normal

implies a range of small variations from the ideal this ideal being not very

commonly encountered.

Normality can be portrayed.

Statistically – as depicted in figure.

- Functionally.

- Evolutionally.

Therefore, one should understand the term variability and its clinical

implications. Also according to Moyers, misuse of the concept of normality has

led to many problems in clinical orthodontics, particularly in treatment planning.

These are the few additional variables of growth:

- Rate means amount of change / time.

- Direction – this denotes the tendency for growth in a particular plane

space. For ex: The face grows downward and forwad.

- Distance curve v/s velocity curve.

Timing of Growth:

The timing of developmental events vary and are mainly controlled by

genetic factors, yet altered by the environment.

Implications:

There are – sex related difference in timing of events

- Spurts.

- Calcification

- Ossification.

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Therefore, timing of a particular therapy should take into account these

variations due to timing.

Growth Accelerations (Spurts) – A spurt is defined as growth acceleration upto

a maximum, where the annual amount of growth exceeded the previous one at

least by 0.7mm – Erkstrom.

Normal spurts as given by Woodside (Figure 3).

i) Infantile spurt – at 3 years.

ii) Juvenile spurt – 7-8 years (Females); 8-10 years (Males)

iii) Pubertal spurt – 10-11 years (Females); 18-15 years (Males).

MECHANISMS OF GROWTH

Growth takes place at the cellular level via three mechanisms:

Hyperplasia (Increase in number)

Cell Hypertrophy (Increase in size)

Secretion of extracellular matter.

- Soft tissue growth occurs by a combination of the above two mechanisms

namely, hypertrophy and hyperplasia and is termed as interstitial growth,

which means that growth occurs at all points within the tissues. However,

in hard tissues namely bone, growth takes place by direct apposition i.e. at

the surfaces it must be known that interstitial growth is not possible within

bone. However, interstitial growth is the one which contributes to the

overall skeletal growth as most of the bones are modeled from cartilage. In

bone, the resting cell is termed as osteocyte capable of differentiating into

osteoblast.

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Osteoblast – bone forming

Osteocyte

Osteoclast – bone removal

Interplay of osteoblastic and osteoclastic activity result in bone remodeling

figure.

In the soft tissues, there is an important interaction between the epithelium

and the mesenchyme:

- Interactive control

- Epithelium

Stimulation

Mesenchyme

Differentiation

This kind of interrelationship is quite significant during the closure of

various facial processes during embryonic development. A classic example to

depict this would be the fusion of the palatal shelves at the midline.

Mechanisms of Growth in Hard Tissues

The bone growth mechanisms are primarily two:

a) Endochondral which is the primary means of ossification in the entire body

which is the chief mode of ossification within the craniofacial complex.

Endochondral ossification – In this variety of ossification, bone forms by

replacing cartilage. This cartilage acts as an intermediary.

Mesenchyme – Cartilage cells Hypertrophy and calcification

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Invasion by Degeneration of cartilage cells.

Osteogenic tissues Replacement by bone (Figure)

Endochondral bones are seen in areas of compression.

The cartilage bone interfaces is important because :

i) Cartilage offers flexibility pressure tolerance acts as a growth site.

ii) Interstitial growth is possible.

Endochondral bones in the skull and facial regions are:

- Synchondroses at the cranial base.

- Nasal septal cartilage.

- Condylar cartilage.

b) Intramembranous bone formation – This differs from endochondral

ossification in that there is no cartilaginous intermediary and bone

formation can directly proceed from mesenchymal tissue.

Undifferentiated mesenchymal cells

Transformation

Osteoblasts.

Osteoid matrix – secondary osteon

Bone – calcification

This is the :

- Predominant mode of ossification in the skull (cranial vault).

- Periosteal bone is always intramembranous.

- Occurs in areas of tension.

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- Constant remodeling is possible and therefore forms orthodontic tooth

movement the basis for:

The important regions of intramembranous ossification within the cranial

complex are:

- Cranial vault.

- Bones in the facial complex; ex: zygoma.

- Maxilla.

- Mandible, except the condyle.

Bone Growth Mechanisms

a) Remodelling : A process involving deposition and resorption

occurring on the opposite ends.

b) Displacement

i. Primary due to enlargement of the bone itself.

ii. Secondary due to enlargement of adjacent bones.

c) Rotation – diagonally placed areas of deposition and resorption.

d) Remodelling and displacement combination occurring together are

the basic mechanisms in the enlargement and movement of bone.

Measurement and Prediction of Growth

Types of Growth Data:

a) Opinion – One person’s biased guess. It is the crudest form of data;

however should not be outrightly derided.

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b) Observations – itself for studying all or none phenomena.

c) Rating and Rankings – comparison with conventional rating scales. The

commonest for there is facial type.

d) Quantitative measurements

Direct data Indirect growth measurements Derived data

Methods of Gathering Data:

A) Longitudinal measurement made of the same person at regular

intervals through time.

Advantages :

a)Variability within a groups is put in proper perspective.

a) Assessment of specific developmental pattern possible.

b) Temporary temporal problems are smoothed out.

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Disadvantages :

i) Time consuming.

ii) Expensive.

iii) Attrition.

iv) Averaging.

b) B) Cross sectional Data: Measurements of different individuals or different

samples made and studied at different periods.

Advantages:

a. Quick.

b. Cost effectiveness.

c. Statistically significant data for large populations.

d. Repetition of studies is possible.

e. Can be performed on cadavers skeletons etc.

c) Semilongitudinal data – This type of data collection is the preferred one,

since it combines the advantages, longitudinal and cross sectional.

Measurement Approaches:

a) Craniometry – Basic of anthropology

o Precise measurements on dry skulls.

o However, data is always cross sectional.

b) Anthropometry – Measurements of skeletal variables in living individuals

as well; based on various skeletal landmarks.

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o Longitudinal data

c) Cephalometry – Important clinically to the orthodontist in order to evaluate

a patients skeletal ( and soft tissue) growth at a given period of time.

o Longitudinal data.

o However, only two dimensional representation.

Experiemental Approaches:

a) Vital Staining – Dyes that stain mineralizing hard tissues and occasionally

soft tissues as well.

Introduced by John Hunter ; Belchier in 1736.

o Alizarin.

o Tetracycline.

o Radioactive markers – to a limited extent.

b) Implant Radiography: Implants (inert metal pins) placed in the bone,

which get incorporated.

o Bjork.

o Has remarkable improved the accuracy of longitudinal cephalometric data.

o Rotations of mandible appreciated now, with this technique.

Maturation Indicators

- Hand wrist radiographs.

- Tooth calcification.

o Canine

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o Third molars.

- Onset of puberty.

- Cervical vertebrae.

- Prediction of growth

- Finite element

Clinical Implications

a) Head form as the basis for malocclusion.

b) Working with growth with the knowledge of growth fields; phenomenon

of relapse.

c) Planning of therapy.

i) To evaluate the causative of the abnormality.

ii) To time the individual and accordingly plan the mode of

therapy.

iii) Phenomena of compensations.

Skeletal Dentoalveolar

d) Predict efficacy of therapy.

e) To understand the evolution of dysmorphogenetic changes.

Evolution of Human Head Form

Human head form varies significantly from its evolutionary predecessors

mainly to accommodate the enlarged brain.

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Through the overall structure remains the same, the obvious alterations

should be properly understood.

a) Marked flexures in the cranial floor.

b) Vertical deposition of the spinal cord.

c) Orbital positioning.

d) Relative decrease in jaw size.

e) Replacement of snout by an almost hairless integument, with advanced

vasomotor control.

f) Orbital rotation with decreased anatomic region between the eyes.

g) Cheek bones placed in wide bilateral regions.

Functional Matrix Theory of Moss

Moss (1960, 1962, 1964, 1969) proposed that the stimuli of the growing

skeletal tissues lie within the adjacent soft tissues – termed the functional

matrices.

He improved on the concept proposed by Vander Klaauw – Bones

composed of various cranial units – “Functional cranial components”, their

growth being relatively independent.

The classic statement of Moss (1981) goes as follows:

“The origin, growth and maintenances of all skeletal tissues and organs are

always secondary, compensatory and obligatory responses to temporarily and

operationally prior events or processed that occurs in specifically related non

skeletal tissues, organs or functioning spaces (functional matrices).

Which implies that:

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- Skeletal growth occurs passively in response to soft tissue growth. Ex:

Growth of the cranial vault, Growth of the coronoid process, growth of the

orbit.

- The soft tissue growth occurs in response to the functional demands of that

particular region.

Components and Concept: The main philosophy of FMH is based on concept

which visualize the craniofacial areas a set of components.

- The head is a region (operationally) within which certain functions occurs

is specifically associated with the functions for ex: The oral cavity –

mastication, speech, taste etc.

- These functions are carried out by the functional cranial components.

- Functional cranial (periosteal) functional matrix.

- Functional cranial components get arranged and are seen as two capsules

in the craniofacial region namely:

a) Neurocranial capsule.

b) Orofacial capsule.

- These capsules contain capsular matrices which would include non skeletal

tissues – Ex: Brain and leptomeninges or functioning spaces – Ex:

Dronasopharygeal space.

- Growth includes changes in size and shape as well as change in spatial

positions of time.

- Increase in size occurs due to interactions between a periosteal matrix and

its skeletal unit, which is termed as transformation.

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- Changes in space occurs because of the increase in capsular matrices

termed as translation.

Let us now look at each these components in detail:

Functional Cranial Components:

As mentioned earlier, these are comprised of:

a) Skeletal unit.

b) Functional matrix.

a) Skeletal unit : These may be comprised of bone, cartilage or tendinous

tissue. Their function is to protect and / or support its functional matrix.

Derivatives – If a bone is in turn made up of a number of small skeletal

components, then the bone is termed as a macroskeletal unit. The individual

skeletal components – Microskeletal unit.

For example, Angular microskeletal unit, coronoid microskeletal unit.

- The microskeletal units are relatively independent to a variable extent.

Thus, for the mandible, we can distinguish:

a. Coronoid microskeletal unit.

b. Angular microskeletal unit.

c. Alveolar microskeletal unit.

d. Basal microskeltal unit.

This kind of segregation of a bone is mainly on the basis of the associated

soft tissue attachments or structures within

“FUNCTIONAL CRANIAL COMPONENT”(By Melvin Moss)

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SKELETAL UNIT FUNCTIONAL UNIT

MICRO-SKELETAL MACRO-SKELETAL PERIOSTEAL CAPSULAR MATRIX MATRIX

E.g., Coronoid e.g. entire e.g. muscles e.g. Neurocranial angular etc. endocranial glands nerves capsule

surface of vessels fat, oro-facial capsulecalvarium teeth etc.

MICRO-SKELETAL UNITS OF THE MANDIBLE

a) Coronoid.

b) Condylar.

c) Angular.

d) Basal.

e) Alveolar.

b) Functional Matrices

Functional matrix : It is the functioning component of a cranial unit. Includes all the

soft tissue (non-skeletal) units. The non skeletal units would include hard tissues like

teeth and cartilage also.

Types of Functional Matrices:

i) Periosteal matrix.

ii) Capsular matrix.

i) Periosteal Matrix : It comprises of all non-skeletal functioning units

adjacent to the skeletal unit. Ex: The muscles, glands, nerves, vessels etc.

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These functional matrices act to alter either or both size and shape

of the skeletal units per se. ex: Role of temporalis in regulating the size and

shape of the coronoid process.

This means that it is the functioning which occurs first and bone growth is

just in response.

Periosteal matrices are capable of inducing deposition and resorption in the

skeletal unit. Enlow has termed this as growth remodeling, while Moss has

termed this same process as tranformation.

ii) Capsular Matrices : All functional cranial components

are organized in the form of capsules. In the craniofacial region, 4 capsular

can be identified:

1) Neurocranial capsule.

2) Orofacial capsule.

3) Otic capsule.

4) Orbital capsule.

The capsules are envelopes surrounding their respective capsular matrices.

Capsular matrices may exist as volumes.

Capsular are sandwiched between two covering layers.

Growth of skeletal units in space (translation)

results because of the expansion of the capsular matrices.

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This phenomenon of translation has been termed as displacement by

Enlow, we shall limit to the elaboration of the neurocranial and orofacial capsules

only.

1) Neurocranial capsule : It is a capsule between skin and

duramater enclosing the neurocranium.

2) Its capsular matrix is made up of the brain, the

leptomeninges, and cerebrospinal fluid.

3) This capsule originates during the foetal period where in

the foetal neural mass surrounded by the neural capsule.

4) Growth of the neural mass causes expansion of the capsule

– (mitotic activity of the connective tissue elements of the capsule).

5) Due to this growth, the entire composition (all related

cranial elements) gets passively translated.

6) At the same time, transformation is also taking place in

response to this passive displacement.

Oro-facial Capsule:

The oro-facial capsule surrounds and protects the

oronasopharyngeal spaces. These spaces are the capsular matrices for the oro-

facial capsule.

This capsule is surrounded by the skin and the mucous

membrane on either side.

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The oro-facial capsule originates by the process of

enclosure. The important phases during its origin are as follows:

First arch swellings enclose to form the primordial

oro-nasal cavity, followed by a.

Rupture of buccopharyngeal membrane.

Elevation and fusion of the bilateral palatal processes

then ensues.

The volumetric growth of these spaces that is the

primary morphogenetic event in facial skull growth.

Patency of airway is maintained by the airway

maintenance mechanism.

Growth of the functioning spaces causes an increase

in the size of the capsule (mitosis of both epithelial and mesenchymal

element).

There is a passive movement of the functional cranial

component.

This displacement brings about compensatory

transformation of skeletal units in response to an alteration in the periosteal

matrices. The transformation is necessary to maintain proper articular

contacts.

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Interaction between of Functional Components

Capsular matrix growth Capsular growth } Translation Total Growth Changes

Periosteal matrix growth Skeletal unit growth } Transformation

In short : Soft tissue growth governs skeletal growth and the related growth

movments.

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CRANIOFACIAL GROWTH THEORIES

In this concluding section, we shall look at the following:

- Evolution of the various hypothesis.

- The genetic concept, which includes.

a) Sicher’s ‘Sutural Dominance Theory’.

b) Scott’s Cartilagenous Theory.

- Functional Matrix theory of Moss.

- The Servosystem Theory – also called the Cybernetic theory of Petrovic.

As scientists (biologists) started delving more into the question of ‘how’

rather than ‘what’ in relation to growth and development, there was an emergence

of a distinctive field, termed the craniofacial biology.

As defined by Carlson Craniofacial biology is the study of the growth,

function and adaptation, both phylogenetically and ontogenetically, of the

craniofacial skeleton and related structures’.

Evolution of Various Growth Theories : As depicted in the diagram, a theory is a

part of a Paradign Kuhn has defined a Padarigm is a conceptual scheme that

encompasses individual theories and is accepted by a scientific community as a

model and foundation for further research.

- A theory may be defined as a scheme or a system of ideas to explain

observed facts.

- A hypothesis is a supposition made as the basis of reasoning.

- A fact is a recorded scientific observation.

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Craniofacial biology has had no shortage of theories regarding facial

growth. Generally, these theories occupy a continuum ranging from a complete

emphasis on intrinsic genetic factors as the control mechanisms, to a total denial

of the genetic factors and a total reliance on the functional determinants.

Also, this continuum is also closely related to time, with distinct cras

correlating with distinct paradigms.

I) 1920-1940 – The Genomic Paradigm : Craniofacial

research during this period was based primarily on the study of structure of

the craniofacial skeleton, with little or no emphasis on function. It was on era

essentially static and researchers like Brodie, Sicher etc. stating that growth

of the craniofacial skeleton as being largely genetically predetermined.

II) 1940-1960 – The ‘Pre-revolutionary Era’ – coined

by Pruzansky : During this period, animal experimental research gained

momentum. Craniofacial researchers noted that there is a vast amount of

variation within the facial region than would occur due to genetically

determined patterns and much of this variation could be the results of

modifying influences of the environment.

Though the genomic paradigm, through the researchers like Scott, there was a

dominant shift due to the pioneers works of Melvin Moss. There was also an

increased interrelation developing between craniofacial biology and other

structural sciences like comparative anatomy, embryology etc.; this being termed

as a structures functional approach.

EVOLUTION OF THE HYPOTHESIS

PARADIGM

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THEORY

HYPOTHESIS

Paradigms in Craniofacial Biology :

- 1920-1940

- 1940-1960

- 1960-1980

- 1980-onwards

III) 1960-1980 – Evolution of the Functional Paradigm :

The functional matrix hypothesis (FMH) proposed by Moss and Young and

Moss and Salentijin paved way for the new paradigm, termed as the

functional paradigm. Also the serious questioning of the rationale of the

genomic paradigm by basic scientist helped the functional paradigm to

establish itself.

This does not imply that the genomic paradigm has completely lost

ground. In fact, it is beyond doubt that genes do play a major role in craniofacial

growth.

Thus, there existed two mutually conflicting paradigms, each on trying to

establish its supremacy.

IV) 1980’s onwards – The Era of Rational Confluence :

As the two paradigms refuted each other completely, the entire jigsaw could

not be put together entirely.

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FACT

This led the craniofacial biologists to seek a composite explanation for the

growth mechanisms. For ex: Van Limbhorg tried to integrate both genetic and

epigenetic mechanisms together. Also the fact that Moss himself in 1997, stated

that both the genetic and epigenetic factors are equally important and put forth a

new theory called the “Complexity Theory’, underlines this congregation of ideas.

We shall now sequentially assess critically each of the prominent theories

that have been put forth.

Growth Centres:

Places of endochondral ossification with a tissue separation force – Baume.

Contributing to the increase of skeletal mass – Koshi.

Prototype – Epiphyseal plate.

Assumed cranial growth centers:

a) Sutures.

b) Cartilage of the nasal septum.

c) Condylar cartilage.

d) Cranial base synchondroses.

Criteria for terming a growth center:

i) Inherent growth potential.

ii) Independence

iii) Extirpation should cause profound altered and depleted growth.

iv) Should be similar to the prototype.

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Sicher’s Theory of Sutural Dominance

Weimann and Sicher (1947) inferred from their studies using vital dyes

that sutures were causing most of the growth. In Sicher’s words. “The primary

event in sutural growth is the proliferation of the connective tissues between the

two bones. If the sutural tissue proliferates, it creates the space for oppositional

growth at the borders of the bones”.

Other proponents of sutures as growth centers were Massler, Baer, Prabl

etc.

Their visualization of the suture was as a three layered structures and that

interstitial connectives tissues growth caused separation and replacement

of the proliferating connective tissues was necessary for the functional

maintenance.

Sicher also proposed that mandibular growth is controlled by a similar

intrinsic genetic potential for growth of the mandibular condyles.

Their visualization of growth in the nasomaxillary area was:

‘Growth at the sutures moves the nasomaxillary complex downward and

forward and growth of condyles keep pace in the same directions, thereby

creating space for alveolar process growth and the eruption of teeth’.

Thus, the primary importance was given to sutural growth, which was

assumed to be under genetic control. The remnant mandibular growth was again

believed to be determined genetically, the principal area being the condyle. Little

or perhaps no role was attributed to the environmental factors.

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This theory was quite popular at that time; so much so that people gave

up the idea of altering growth, even to a small extent. However, with experiments

which disproved the idea of sutures being growth centers and the surge in the

functional dogma, this theory lost ground.

Evidences against Sicher’s Theory :

- Autotransplants of sutures fail to growth.

- The shape and growth within this sutures is dependent on external stimuli.

Ex: sutural expansion or closure can be attempted.

- Extirpation of sutures does not show appreciable alterations in growth in

the areas from where they have been removed. This was demonstrated by

Moss.

- Finally, sutures do not resemble epiphyseal plates – both histologically or

biochemically.

- The present concept about sutures is that : sutures are growth sites, they are

five layered structures, show adaptability to extrinsic stimuli.

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PROCESS CONTROL

CRANIAL DIFFERENTIATION

Intrinsic Genetic Factors

Local Epigenetic Factors

General Epigenetic Factors

Local Environmental Factors

General Environmental Factors

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PROCESS CONTROL

CHONDROCRANIAL GROWTH

Intrinsic Genetic Factors

Local Epigenetic Factors

General Epigenetic Factors

Local Environmental Factors

General Environmental Factors

DESMOCRANIAL GROWTH

SUTURAL GROWTH

PERIOSTEAL GROWTH

SCOTT’S VIEW

Scott’s Cartilaginous Theory

Scott (1956) suggested that hyaline cartilage has certain properties which

allow it to determine growth in the cranial base and the nasal areas, and this

growth establishes an under pinning for the shell of the face to be formed

intramembraneously around this cartilage.

In other words, the cephalic cartilages, namely the synchondrosis, the

septal cartilage and the condylar cartilage have inherent growth potential. Added

to this is the adaptive role of sutures, which adjusts as these aforementioned areas

growth.

The remaining intramembraneous growth that occurs around this template

passive.

Evidence favouring this theory:

- Disturbances in the nasal septum affects growth of the midface

considerably

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o Rabbit experiments.

o Cleft palate – in human (Injury)

- On autotransplantation, some growth may occur – Study by Koski and

Ronning.

Recent Concepts in Functional Matrix Hypothesis

Revised Statement

The developmental origin of all cranial structural elements and all their

subsequent in size and shape, as well as their maintenance in being are always,

without exception, secondary, compensatory and mechanically obligatory

responses to temporally and operationally prior demands to their related cephalia

non-skeletal cells, tissues, organs and operational volumes.

Moss, initially points out the constraints of the previous version of the

Functional Matrix Hypothesis is (FMH) and goes on to explain how, in these

years (1980 onwards) they have been overcome.

The constraints according to Moss are:

- Methodological constraint – due to macroscopic measurements which use

arbitrary reference phases like the : SN or FH plane – These have been

overcome by the use of Finite Element Method (FEM).

- Hierarchical Constraint – all previous FMH versions were suspended or

sandwiched between the two hierarchical levels of multicellular and

subcellular. This has been overcome in the version by the establishment of

a linkage between all levels.

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- This present version (new) deals with the responses of the periosteal

mtrices only.

This new version can be understood better if one understands the following

cellular events:

a) Adaptation is a tissue process consisting of deposition and maintenance are

functions of relatively large groups (whorts) of osteoblasts.

- Adjacent adaptational tissue surfaces simultaneously show deposition,

resorption and maintenance.

It is well known that the previous version implies that skeletal unit

adaptation takes place in response to stimulation of the functional matrices.

- But ho does the stimulation, which occurs at the periosteum reach the

functioning cell units?

- How is it interpreted and what is the resultant?

- How is this output expressed at the tissue level?

All these and pertinent questions seem to be clarified by:

a. The process of mechanotransduction.

- Bone cell functioning multicellularly as a connected cell network.

Mechanotransduction

Vital cells are ‘irritable’ and respond in alteration in their external

environment. This mechanosensing property requires.

- Mechanoreception – transmission from ‘extra’ to ‘intra’

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- Mechanotransduction – transformation of energetic and / or informational

content into an intracellular signal.

When external loadings are applied to the bone tissue there is some

deformation of the bone matrix (extracelular) and bone cells.

- Osteocytes and osteoblasts are competent for intracellular stimulus

reception; transduction and for subsequent intercellular transmission.

Osseous mecanotransduction may involve the complementary process of:

i) Mechanical transduction.

ii) Ionic transduction.

i) Mechanical transduction : It has been shown that a series of

macromolecular mechanical levels exist, which are capable of transmitting

information from the strained matrix to the bone cell nuclear membrane.

This molecules is supposed to be physically continuous from the

extracellular collagen matrix to the intracellular cytoskeletal actin; which in turn

is connected to the nuclear membrane.

The so-described molecular lever chain can provide a physical stimulus

able to activate the osteocytic genome.

ii) Ionic transduction : Osteocytes may contain two types of ionic

channels.

A) Voltage activated ionic channels, which allow certain ions

to flow across the membrane and this transmembrane flow acts as a

transductive process by generating osteocytic action potentials (Figure).

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B) Stretch activated ionic channels – In strained bone tissues

and in fibroblasts too, stretch activated channels exist. When active, they

permit passage of a certain sized ion(s) like Ca++ , K+ , Na+ etc. Such ionic

flow may modulate membrane potential and also to some extent regulate

Ca++ influx (Figure).

The other possible Ionic transduction mechanisms are:

1) Electric field strength – Bone responds to exogenous

field strengths and there seems to be a parallel between these and

endogenously produced fields by muscles.

2) Electrokinetic – These are bound and unbound

charges which exist in bone field(s) and are of streaming potential origin.

These charges can initiate both osteoclastic and osteocytic action

potentials.

Considerations in Mechanotransduction - Mechanotransduction principle is

based on the following factors:

- Normal skeletal muscle strains are attached intermittently.

- Dynamics of skeletal muscle contraction fit nicely with energetic

requirements for bone cell responsiveness.

o Both stimulatory and regulatory.

- Bone cells may be stimulated directly via the channels or indirectly by

electrokinetic phenomena.

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‘Bone seems to be “tuned” to the skeletal muscle’ (Skeletal Units) –

Periosteal Matrix.

As Moss Puts it :

“When both ionic and mechanical transductive processes are conceptually

and operationally combined with the data of both electric field effects and of

contraction frequency energetics they provide a logically sufficient biophysical

basis support for the hypothesis of epigenetic regulation of skeletal tissue

adaptation”.

Bone as an Osseous Connected Cell Network (CCN)

All bone cells, except osteoclasts are extensively connected by gap

junctions.

Gap junctions are seen where the plasma membranes of markedly

overlapping canalicular processes meet.

These canaliculi are extensions of the osteocytes which lie in the bony

matrix.

The canalicular processes are seen to interconnect neighbouring cells

processes.

Gap junctions also connect superficial osteocytes to periosteal and

endosteal osteoblasts; and vertically the periosteal osteoblasts with preosteoblastic

cells.

Gap junctions are seen to permit movement of the ions, small molecules

and even the fluorescent dyes.

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They can be termed ‘electrical synapses’, which permit bi-directional

signal traffic.

Bone tissue seems to be interconnected through layers as a network, where

parallel distributed signal processing occurs.

The CCN cells are organized into layers, the chief units being ‘input’ layer,

an output layer and a series of intermediate or ‘hidden’ layer(s).

Each cell in any layer may simultaneously receive several (weighted)

stimuli.

Within each cell, all weighted inputs are summed independently.

This sum, if it crosses certain threshold values, successful mechano-

transduction occurs.

This signal is transmitted identically to all the hidden layers.

Similar processes of weighted summation, comparison and transmission

occur in the intermediate cells, till the final layer of osteoblasts is reached.

The outputs of these superficial cells determine the site, rate, direction,

magnitude and duration of the specific adaptive response.

Epigenetic process of loading

Loading as a process loading is unquestionably of greatest importances at

the clinically significant structural levels.

Loading acts not only at the tissue levels, but also at cellular and

subcellular levels.

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The epigenetic mechanisms involved include:

- Regulation of multicellular tissue morphogenesis – via extracellular matrix

and transduction.

- Controlling osteoblastic gene expression through mechanical layers

altering cell shape.

At the tissue levels also, epigenetic mechanisms have been noted for ex: in

cartilage.

At the organ level, the vital role of articular function is well known.

Regulation of periosteal matrices:

- Mechanical loads – Phenotype.

- Neutrophism – Genotype.

New Insight into the Role of Periosteal Matrices :

Considering that the morphogenetic primacy of the periosteal matrices is

accepted, one can logically deduce the following:

- Physical loading tends to deform bone tissue and invoke the skeletal unit

adaptive response. Ex: temporalis.

- Mechanoreception occurs chiefly, through some periosteal osteoblasts may

be directly stimulated.

- Strain is believed to be a competent stimulus and the attributes may vary

with:

o Type of loading.

o Fine tuning.

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- Mechanotransduction, either of ionic or mechanical nature occurs

throughout the osseous CCN.

- Output or the adaptive response is via the signals which get transduced

through summation.

Evolution of the Complexity Theory of the FMH

Complexity theory provides description of the behaviour of complex

biologic systems which exist as ‘ensembles’ and not as clusters of individual cells

and extracellular substances.

In this system a functional cranial unit is termed as Complex Adaptive System

(CAS):

Complexity Theory (CT) involves processing of both genomic and

epigenetic information by the CAS.

It also implies that growth and development, to a significant extent exhibit

random behaviour – therefore, are nonlinear processes and is not fully

predictable.

The highly ordered morphological properties of adult biologic system

result from a series of spontaneous and self organized processes and mechanisms.

Such self organizing events can create phenotypic variability under genetic and

epigenetic conditions.

The operation of complexit has been termed by him as “Environmental

factors thus play a decisive role. But it is the organism itself that, as an integrated

system dictates the nature of each and every developmental response”.

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‘The living organism self organizes on the basis of its own internal

structuring, in continuous interaction with the environment in which it finds

itself’.

Moss has also compared between the genetic and epigenetic mechanisms.

- He rebukes the geneticists claim of high genetic control – odontogenic

regulation by epigenesis.

- The genetic thesis is denied because it is reductionist and molecular.

- He says that the epigenetic antithesis as of how is integrative, seeking to

clarify the causal chain between phenotype and the genoms.

- The resolving synthesis, however, he says is to consider both the intrinsic

(genetic) and the extrinsic (epigenetic) processes and mechanisms integrate

and provide the necessary and sufficient causes of growth and

development.

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Thesis (Genetic) Antithesis (Epigenetic)

Resolving Synthesis

Complexity Theory

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