GROWTH AND DEVELOPMENT A Birds 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 deve o!"ent in #enera $ we sha i) ii) iii) oo% at the &o owin# as!e'ts(

What is growth? What is development? Why do we need to study about growth development. ormal features of growth and development. a. !ifferentiatial growth. b. "attern. c. #ariability. d. Timing$ rate and direction. e. ormality.

iv)

%echanisms of growth in: & & 'oft tissues. (ard tissues.

v) vi) vii)

)volution of the human head form. %easurement and prediction of growth. *linical implications.

What is growth? What is development? Though closely related growth and development are not one and the same.

De&inition o& #rowthGrowth(

& & Growth usually refers to an increase in si,e - "rofile .Todd). Growth may be defined as the normal change in amount of living substance - %oyers.

De&inition o& deve o!"entDeve o!"ent(

& !evelopment connotes a maturational process involving progressive differentiation at the cellular and tissue levels - )nlow. & !evelopment refers to all naturally occurring progressive$ se/uential and unidirectional changes in the life of an individual from its e0istence as a single cel to its elaboration as a multifunctional unit terminating in death %oyers. & & !evelopment is a progress towards maturity .Todd). %orphogenesis : 1 biologic process having an underlying control at the cellular and tissue levels - )nlow. & 1s can be understood from the above definitions$ growth and development are complementary to each other. & 2ne can also draw certain correlations between growth and development.

)o*re ation +etween #rowth and deve o!"ent(

& & Growth emphasi,es the normal dimensional changes during development. 4ecause growth is mainly anatomic5 also /uantitative.

Deve o!"ent #rowth , di&&erentiation , trans o'ation& & !evelopment is mainly physiologic and /ualitative. !evelopment implies an increased speciali,ation wit a decrease in function. Thus$ it is the combination of growth and morphogenesis 'elf %ultiplication. 6 !ifferentiation. 6 2rgani,ation. 7ndividual phenotype.

Why do we need to st.dy #rowth and deve o!"ent/

To have an understanding of the following: a) ormal growth and how it occurs.

b) "atterns of abnormal growth and the reason.s). c) To distinguish between normal and abnormal. d) 8tili,e growth .9working with growth:) to our benefit.

Nor"a 0eat.res o& Growth and Deve o!"ent(

a) !ifferential growth - different tissues and in turn different organs grow at different rates. This process is called differential growth. 1s depicted in figure +$ in a normal individual$ the neural tissues grow early in life completing their maturation first$ followed by the lymphoid tissues$ which actually diminish in si,e after puberty. The remaining general body fuses mature later5 the last being the genital tissues. The ma0illa and the mandible follow the general body growth5 the mandible slightly slower than the ma0illa initially but catches up later. 7t is important to know this because a male child who presently with a slight mandibular deficiency at age +3 should be e0pected to have a normal mandibular si,e by age +<&+= years. b) "attern of growth - pattern is a set of constraints$ /uantitative 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 comple0 proportionalities which change wit time. For e0ample : 1t ; months of intrauterine life$ the human foetus is almost <>? of the total body length. This$ for that particular time is normal. 1t birth$ the trunk and limbs$ which were earlier rudimentary have grown faster than the head and therefore the proportion of head si,e to the rest of body length is about 3<&;>?. )ventually$ at adulthood$ the head si,e is @ust about +3? .Figure 3)5 these reflect the comple0ity in proportions$ which change with time.

7n relation to differential growth and indicative of a normal growth pattern$ is the cephalocaudal gradient of growth. & "redictability of growth pattern : as can be inferred from figure 3$ a specific kind of proportionality e0ists at a particular time and progresses towards another at the ne0t time frame$ with a slight variations. & This has important implications : 7n prediction of the future growth pattern .using growth charts for that population) and to recogni,e 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 e0tremities). This can be amply inferred from figure 3. & 7t is interesting that even within the craniofacial skeleton$ there e0ists a cephalocaudal gradient5 The skull of an infant occupies almost 3B; rd -;BA of the cranial comple0. The ma0illa grows ne0t and the mandible .being at the caudal end) is the last to grow .Figure ;). 7n orthodontic$ pattern has a morphogenetic as well as a developmental application. & & & %orphogenetic - For e0: the statement he has a *lass 777 facial pattern. !evelopmental - %ohan ha a vertical growth pattern. "atterns can be /uantified in terms of craniofacial constants$ which show invariance.

<

1"! i'ations o& !attern(

& & 1nalysis of morphology. 'tudy of stability of treatment. o two individuals$ with the e0ception of mono,ygotic twins are

#ariability :

alike$ i.e. variation is the law of nature. To e0press variability /uantitatively$ it is useful to categori,e in terms of deviations from the usual pattern. This is done using standard growth charts. The growth charts help in: & & & !etermining whether growth is normal or abnormal. To evaluate growth over a period of time. Growth charts are available for 7ndian population through the 7ndian *ouncil for medical research and Cife 7nsurance *orporation. #ariability of growth may be seen in terms of: a) *hronologic age - variation due to timing and because chronologic age is not a good indicator of growth status. b) )thnic group. c) 'e0es. d) #ariance with time - secular trend. e) 4ody type. Nor"a ity ( ormal refers to what is usually e0pected$ seen or is typical.

7t 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. ormality can be portrayed. 'tatistically - as depicted in figure. & & Functionally. )volutionally. Therefore$ one should understand the term variability and its clinical implications. 1lso according to %oyers$ 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: & & Date means amount of change B time. !irection - this denotes the tendency for growth in a particular plane space. For e0: The face grows downward and forwad. & !istance curve vBs velocity curve.

Ti"in# o& Growth(

The timing of developmental events vary and are mainly controlled by genetic factors$ yet altered by the environment.

1"! i'ations(
There are - se0 related difference in timing of events & & & 'purts. *alcification 2ssification.

Therefore$ timing of a particular therapy should take into account these variations due to timing. Growth A''e erations 23!.rts4 - 1 spurt is defined as growth acceleration upto a ma0imum$ where the annual amount of growth e0ceeded the previous one at least by >.Emm - )rkstrom. ormal spurts as given by Woodside .Figure ;). i) ii) iii) 7nfantile spurt - at ; years. Fuvenile spurt - E&G years .Females)5 G&+> years .%ales) "ubertal spurt - +>&++ years .Females)5 +G&+< years .%ales).

ME)HAN13M3 O0 GROWTH
Growth takes place at the cellular level via three mechanisms: (yperplasia .7ncrease in number) *ell (ypertrophy .7ncrease in si,e) 'ecretion of e0tracellular matter. & 'oft 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. (owever$ 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. (owever$ interstitial growth is the one which contributes to the overall skeletal growth as most of the bones are modeled from cartilage. 7n bone$ the resting cell is termed as osteocyte capable of differentiating into osteoblast.

2steoblast - bone forming 2steocyte 2steoclast - bone removal 7nterplay of osteoblastic and osteoclastic activity result in bone remodeling figure. 7n the soft tissues$ there is an important interaction between the epithelium and the mesenchyme: & & 7nteractive control )pithelium 'timulation %esenchyme !ifferentiation This kind of interrelationship is /uite significant during the closure of various facial processes during embryonic development. 1 classic e0ample to depict this would be the fusion of the palatal shelves at the midline.

Me'hanis"s o& Growth in Hard Tiss.es

The bone growth mechanisms are primarily two: a) )ndochondral which is the primary means of ossification in the entire body which is the chief mode of ossification within the craniofacial comple0. )ndochondral ossification - 7n this variety of ossification$ bone forms by replacing cartilage. This cartilage acts as an intermediary. %esenchyme - *artilage cells (ypertrophy and calcification

7nvasion by

!egeneration of cartilage cells.

2steogenic tissues Deplacement by bone .Figure) )ndochondral bones are seen in areas of compression. The cartilage bone interfaces is important because : i) ii) *artilage offers fle0ibility pressure tolerance acts as a growth site. 7nterstitial growth is possible.

)ndochondral bones in the skull and facial regions are: & & & 'ynchondroses at the cranial base. asal septal cartilage. *ondylar cartilage.

b) 7ntramembranous bone formation - This differs from endochondral ossification in that there is no cartilaginous intermediary and bone formation can directly proceed from mesenchymal tissue. 8ndifferentiated mesenchymal cells Transformation 2steoblasts. 2steoid matri0 - secondary osteon 4one - calcification This is the : & & & "redominant mode of ossification in the skull .cranial vault). "eriosteal bone is always intramembranous. 2ccurs in areas of tension.

+>

&

*onstant remodeling is possible and therefore forms orthodontic tooth movement the basis for: The important regions of intramembranous ossification within the cranial

comple0 are: & & & & *ranial vault. 4ones in the facial comple05 e0: ,ygoma. %a0illa. %andible$ e0cept the condyle.

Bone Growth Me'hanis"s

a) Demodelling : 1 process involving deposition and resorption occurring on the opposite ends. b) !isplacement i. "rimary due to enlargement of the bone itself. ii. 'econdary due to enlargement of ad@acent bones. c) Dotation - diagonally placed areas of deposition and resorption. d) Demodelling and displacement combination occurring together are the basic mechanisms in the enlargement and movement of bone.

Meas.re"ent and Predi'tion o& Growth

Types of Growth !ata: a) 2pinion - 2ne personIs biased guess. 7t is the crudest form of data5 however should not be outrightly derided.

++

b) 2bservations - itself for studying all or none phenomena. c) Dating and Dankings - comparison with conventional rating scales. The commonest for there is facial type. d) Juantitative measurements !irect data 7ndirect growth measurements !erived data

Methods o& Gatherin# Data(

1) Congitudinal measurement made of the same person at regular intervals through time. Advantages : a)#ariability within a groups is put in proper perspective. a) 1ssessment of specific developmental pattern possible. b) Temporary temporal problems are smoothed out.

+3

Disadvantages : i) ii) iii) iv) Time consuming. )0pensive. 1ttrition. 1veraging.

b) 4) *ross sectional !ata: %easurements of different individuals or different samples made and studied at different periods.

Advantages: a. Juick. b. *ost effectiveness. c. 'tatistically significant data for large populations. d. Depetition of studies is possible. e. *an be performed on cadavers skeletons etc. c) 'emilongitudinal data - This type of data collection is the preferred one$ since it combines the advantages$ longitudinal and cross sectional.

Meas.re"ent A!!roa'hes(
a) *raniometry - 4asic of anthropology o "recise measurements on dry skulls. o (owever$ data is always cross sectional. b) 1nthropometry - %easurements of skeletal variables in living individuals as well5 based on various skeletal landmarks.

+;

o Congitudinal data c) *ephalometry - 7mportant clinically to the orthodontist in order to evaluate a patients skeletal . and soft tissue) growth at a given period of time. o Congitudinal data. o (owever$ only two dimensional representation.

E5!erie"enta A!!roa'hes(
a) #ital 'taining - !yes that stain minerali,ing hard tissues and occasionally soft tissues as well. 7ntroduced by Fohn (unter 5 4elchier in +E;=. o 1li,arin. o Tetracycline. o Dadioactive markers - to a limited e0tent. b) 7mplant Dadiography: 7mplants .inert metal pins) placed in the bone$ which get incorporated. o 4@ork. o (as remarkable improved cephalometric data. the accuracy of longitudinal

o Dotations of mandible appreciated now$ with this techni/ue.

Mat.ration 1ndi'ators
& & (and wrist radiographs. Tooth calcification. o *anine

+A

o Third molars. & & & & 2nset of puberty. *ervical vertebrae. "rediction of growth Finite element

) ini'a 1"! i'ations

a) (ead form as the basis for malocclusion. b) Working with growth with the knowledge of growth fields5 phenomenon of relapse. c) "lanning of therapy. i) ii) To evaluate the causative of the abnormality. To time the individual and accordingly plan the mode of therapy. iii) "henomena of compensations. 'keletal d) "redict efficacy of therapy. e) To understand the evolution of dysmorphogenetic changes. !entoalveolar

Evo .tion o& H."an Head 0or"

(uman head form varies significantly from its evolutionary predecessors mainly to accommodate the enlarged brain.

+<

Through the overall structure remains the same$ the obvious alterations should be properly understood. a) %arked fle0ures in the cranial floor. b) #ertical deposition of the spinal cord. c) 2rbital positioning. d) Delative decrease in @aw si,e. e) Deplacement of snout by an almost hairless integument$ with advanced vasomotor control. f) 2rbital rotation with decreased anatomic region between the eyes. g) *heek bones placed in wide bilateral regions.

0.n'tiona Matri5 Theory o& Moss

%oss .+H=>$ +H=3$ +H=A$ +H=H) proposed that the stimuli of the growing skeletal tissues lie within the ad@acent soft tissues - termed the functional matrices. (e improved on the concept proposed by #ander Klaauw - 4ones composed of various cranial units - 9Functional cranial components:$ their growth being relatively independent. The ' assi' state"ent o& Moss 267864 #oes as &o ows( 9The 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). Whi'h i"! ies that(

+=

&

'keletal growth occurs passively in response to soft tissue growth. )0: 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 F%( is based on concept which visuali,e 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 e0: The oral cavity mastication$ speech$ taste etc. & & & These functions are carried out by the functional cranial components. Functional cranial .periosteal) functional matri0. Functional cranial components get arranged and are seen as two capsules in the craniofacial region namely: a) eurocranial capsule.

b) 2rofacial capsule. & These capsules contain capsular matrices which would include non skeletal tissues - )0: 4rain and leptomeninges or functioning spaces - )0: !ronasopharygeal space. & Growth includes changes in si,e and shape as well as change in spatial positions of time. & 7ncrease in si,e occurs due to interactions between a periosteal matri0 and its skeletal unit$ which is termed as transformation.

+E

&

*hanges in space occurs because of the increase in capsular matrices termed as translation. Cet us now look at each these components in detail:

0.n'tiona )rania )o"!onents(

1s mentioned earlier$ these are comprised of: a) 'keletal unit. b) Functional matri0. a) 'keletal unit : These may be comprised of bone$ cartilage or tendinous tissue. Their function is to protect and B or support its functional matri0. !erivatives - 7f 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 - %icroskeletal unit. For e0ample$ 1ngular microskeletal unit$ coronoid microskeletal unit. & The microskeletal units are relatively independent to a variable e0tent.

Th.s$ &or the "andi+ e$ we 'an distin#.ish( a. *oronoid microskeletal unit. b. 1ngular microskeletal unit. c. 1lveolar microskeletal unit. d. 4asal microskeltal unit. This kind of segregation of a bone is mainly on the basis of the associated soft tissue attachments or structures within 90:N)T1ONAL )RAN1AL )OMPONENT; (By Melvin Moss)

+G

3<ELETAL :N1T

0:N)T1ONAL :N1T

MICRO !"#$#%A$

MACRO !"#$#%A$

&#RIO!%#A$ MA%RI(

CA&!'$AR MA%RI(

).g.$ *oronoid angular etc.

e.g. entire endocranial surface of calvarium

e.g. muscles glands nerves vessels fat$ teeth etc.

e.g. eurocranial capsule oro&facial capsule

M1)RO*3<ELETAL :N1T3 O0 THE MAND1BLE

a) *oronoid. b) *ondylar. c) 1ngular. d) 4asal. e) 1lveolar. +4 0.n'tiona Matri'es

0.n'tiona "atri5 ( 7t is the functioning component of a cranial unit. 7ncludes all the soft tissue .non&skeletal) units. The non skeletal units would include hard tissues like teeth and cartilage also.

Types of Functional %atrices: i) "eriosteal matri0. ii) *apsular matri0. i) Periosteal Matrix : 7t comprises of all non&skeletal functioning units ad@acent to the skeletal unit. )0: The muscles$ glands$ nerves$ vessels etc.

+H

These functional matrices act to alter either or both si,e and shape of the skeletal units per se. e0: Dole of temporalis in regulating the si,e and shape of the coronoid process. This means that it is the functioning which occurs first and bone growth is

@ust in response. "eriosteal matrices are capable of inducing deposition and resorption in the skeletal unit. )nlow has termed this as growth remodeling$ while %oss has termed this same process as tranformation. ii) can be identified: +) eurocranial capsule. *apsular %atrices : 1ll functional cranial components are organi,ed in the form of capsules. 7n the craniofacial region$ A capsular

3) 2rofacial capsule. ;) 2tic capsule. A) 2rbital capsule. respective capsular matrices. layers. Growth of skeletal units in space .translation) results because of the e0pansion of the capsular matrices. *apsular matrices may e0ist as volumes. *apsular are sandwiched between two covering The capsules are envelopes surrounding their

3>

This phenomenon of translation has been termed as displacement by )nlow$ we shall limit to the elaboration of the neurocranial and orofacial capsules only. +) eurocranial capsule : 7t is a capsule between skin and duramater enclosing the neurocranium. 3) 7ts capsular matri0 is made up of the brain$ the leptomeninges$ and cerebrospinal fluid. ;) This capsule originates during the foetal period where in the foetal neural mass surrounded by the neural capsule. A) Growth of the neural mass causes e0pansion of the capsule - .mitotic activity of the connective tissue elements of the capsule). <) !ue to this growth$ the entire composition .all related cranial elements) gets passively translated. =) 1t the same time$ transformation is also taking place in response to this passive displacement. Oro facial Caps)le: facial capsule. This capsule is surrounded by the skin and the mucous membrane on either side. The oro&facial capsule surrounds and protects the oronasopharyngeal spaces. These spaces are the capsular matrices for the oro&

3+

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. then ensues. Dupture of buccopharyngeal membrane. )levation and fusion of the bilateral palatal processes

The volumetric growth of these spaces that is the primary morphogenetic event in facial skull growth.

"atency of airway is maintained by the airway maintenance mechanism.

element). component.

Growth of the functioning spaces causes an increase in the si,e of the capsule .mitosis of both epithelial and mesenchymal

There is a passive movement of the functional cranial

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.

33

1ntera'tion +etween o& 0.n'tiona )o"!onents

*apsular matri0 growth *apsular growth L Translation Total Growth *hanges "eriosteal matri0 growth 'keletal unit growth L Transformation 7n short : 'oft tissue growth governs skeletal growth and the related growth movments.

3;

)RAN1O0A)1AL GROWTH THEOR1E3 7n this concluding section$ we shall look at the following: & & )volution of the various hypothesis. The genetic concept$ which includes. a) 'icherIs M'utural !ominance TheoryI. b) 'cottIs *artilagenous Theory. & & Functional %atri0 theory of %oss. The 'ervosystem Theory - also called the *ybernetic theory of "etrovic. 1s scientists .biologists) started delving more into the /uestion of MhowI rather than MwhatI in relation to growth and development$ there was an emergence of a distinctive field$ termed the craniofacial biology. 1s defined by *arlson *raniofacial biology is the study of the growth$ function and adaptation$ both phylogenetically and ontogenetically$ of the craniofacial skeleton and related structuresI. )volution of #arious Growth Theories : 1s depicted in the diagram$ a theory is a part of a "aradign Kuhn has defined a "adarigm is a conceptual scheme that encompasses individual theories and is accepted by a scientific community as a model and foundation for further research. & 1 theory may be defined as a scheme or a system of ideas to e0plain observed facts. & & 1 hypothesis is a supposition made as the basis of reasoning. 1 fact is a recorded scientific observation.

3A

*raniofacial 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. 1lso$ this continuum is also closely related to time$ with distinct cras correlating with distinct paradigms. 7) *+,- *+.- / %he 0enomic &aradigm : *raniofacial research during this period was based primarily on the study of structure of the craniofacial skeleton$ with little or no emphasis on function. 7t was on era essentially static and researchers like 4rodie$ 'icher etc. stating that growth of the craniofacial skeleton as being largely genetically predetermined. 77) *+.- *+1- / %he 2&re revol)tionary #ra3 / coined 4y &r)5ans6y : !uring this period$ animal e0perimental research gained momentum. *raniofacial 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 'cott$ there was a dominant shift due to the pioneers works of %elvin %oss. There was also an increased interrelation developing between craniofacial biology and other structural sciences like comparative anatomy$ embryology etc.5 this being termed as a structures functional approach. EVOL:T1ON O0 THE H=POTHE313

"1D1!7G%

3<

T()2DN (N"2T()'7' F1*T

"aradigms in *raniofacial 4iology: & & & & 777) +H3>&+HA> +HA>&+H=> +H=>&+HG> +HG>&onwards *+1- *+7- / #vol)tion of the 8)nctional &aradigm : The functional matri0 hypothesis .F%() proposed by %oss and Noung and %oss and 'alenti@in paved way for the new paradigm$ termed as the functional paradigm. 1lso the serious /uestioning 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. 7n fact$ it is beyond doubt that genes do play a ma@or role in craniofacial growth. Thus$ there e0isted two mutually conflicting paradigms$ each on trying to establish its supremacy. 7#) *+7-3s on9ards / %he #ra of Rational Confl)ence : 1s the two paradigms refuted each other completely$ the entire @igsaw could not be put together entirely.

3=

This led the craniofacial biologists to seek a composite e0planation for the growth mechanisms. For e0: #an Cimbhorg tried to integrate both genetic and epigenetic mechanisms together. 1lso the fact that %oss himself in +HHE$ stated that both the genetic and epigenetic factors are e/ually important and put forth a new theory called the 9*omple0ity TheoryI$ underlines this congregation of ideas. We shall now se/uentially assess critically each of the prominent theories that have been put forth.

Growth )entres(
"laces of endochondral ossification with a tissue separation force - 4aume. *ontributing to the increase of skeletal mass - Koshi. "rototype - )piphyseal plate. Ass)med cranial gro9th centers: a) 'utures. b) *artilage of the nasal septum. c) *ondylar cartilage. d) *ranial base synchondroses. Criteria for terming a gro9th center: i) 7nherent growth potential. ii) 7ndependence iii) )0tirpation should cause profound altered and depleted growth. iv) 'hould be similar to the prototype.

3E

3i'hers Theory o& 3.t.ra Do"inan'e

Weimann and 'icher .+HAE) inferred from their studies using vital dyes that sutures were causing most of the growth. 7n 'icherIs words. 9The primary event in sutural growth is the proliferation of the connective tissues between the two bones. 7f the sutural tissue proliferates$ it creates the space for oppositional growth at the borders of the bones:. 2ther proponents of sutures as growth centers were %assler$ 4aer$ "rabl etc. Their visuali,ation 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. 'icher also proposed that mandibular growth is controlled by a similar intrinsic genetic potential for growth of the mandibular condyles. Their visuali,ation of growth in the nasoma0illary area was: MGrowth at the sutures moves the nasoma0illary comple0 downward and forward and growth of condyles keep pace in the same directions$ thereby creating space for alveolar process growth and the eruption of teethI. 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. Cittle or perhaps no role was attributed to the environmental factors.

3G

This theory was /uite popular at that time5 so much so that people gave up the idea of altering growth$ even to a small e0tent. (owever$ with e0periments which disproved the idea of sutures being growth centers and the surge in the functional dogma$ this theory lost ground.

Eviden'es a#ainst 3i'hers Theory(

& & 1utotransplants of sutures fail to growth. The shape and growth within this sutures is dependent on e0ternal stimuli. )0: sutural e0pansion or closure can be attempted. & )0tirpation of sutures does not show appreciable alterations in growth in the areas from where they have been removed. This was demonstrated by %oss. & 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 e0trinsic stimuli.

3H

PRO)E33

)ONTROL 7ntrinsic Genetic Factors Cocal )pigenetic Factors General )pigenetic Factors

)RAN1AL D100ERENT1AT1ON

Cocal )nvironmental Factors General )nvironmental Factors

;>

PRO)E33

)ONTROL 7ntrinsic Genetic Factors

*(2 !D2*D1 71C GD2WT( '8T8D1C GD2WT( ")D72'T)1C GD2WT(

Cocal )pigenetic Factors General )pigenetic Factors Cocal )nvironmental Factors General )nvironmental Factors

!)'%2*D1 71C GD2WT(

3)OTT3 V1EW

3'otts )arti a#ino.s Theory

'cott .+H<=) 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. 7n other words$ the cephalic cartilages$ namely the synchondrosis$ the septal cartilage and the condylar cartilage have inherent growth potential. 1dded to this is the adaptive role of sutures$ which ad@usts as these aforementioned areas growth. The remaining intramembraneous growth that occurs around this template passive. )vidence favouring this theory: & !isturbances in the nasal septum affects growth of the midface considerably

;+

o Dabbit e0periments. o *left palate - in human .7n@ury) & 2n autotransplantation$ some growth may occur - 'tudy by Koski and Donning.

Re'ent )on'e!ts in 0.n'tiona Matri5 Hy!othesis

Revised !tatement The developmental origin of all cranial structural elements and all their subse/uent in si,e and shape$ as well as their maintenance in being are always$ without e0ception$ secondary$ compensatory and mechanically obligatory responses to temporally and operationally prior demands to their related cephalia non&skeletal cells$ tissues$ organs and operational volumes. %oss$ initially points out the constraints of the previous version of the Functional %atri0 (ypothesis is .F%() and goes on to e0plain how$ in these years .+HG> onwards) they have been overcome. The constraints according to %oss are: & %ethodological constraint - due to macroscopic measurements which use arbitrary reference phases like the : ' or F( plane - These have been overcome by the use of Finite )lement %ethod .F)%). & (ierarchical *onstraint - all previous F%( 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.

;3

&

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) 1daptation is a tissue process consisting of deposition and maintenance are functions of relatively large groups .whorts) of osteoblasts. & 1d@acent adaptational tissue surfaces simultaneously show deposition$ resorption and maintenance. 7t is well known that the previous version implies that skeletal unit adaptation takes place in response to stimulation of the functional matrices. & 4ut ho does the stimulation$ which occurs at the periosteum reach the functioning cell units? & & (ow is it interpreted and what is the resultant? (ow is this output e0pressed at the tissue level?

1ll these and pertinent /uestions seem to be clarified by: a. & The process of mechanotransduction. 4one cell functioning multicellularly as a connected cell network.

Me'hanotransd.'tion
#ital cells are MirritableI and respond in alteration in their e0ternal environment. This mechanosensing property re/uires. & %echanoreception - transmission from Me0traI to MintraI

;;

&

%echanotransduction - transformation of energetic and B or informational content into an intracellular signal. When e0ternal loadings are applied to the bone tissue there is some

deformation of the bone matri0 .e0tracelular) and bone cells. & 2steocytes and osteoblasts are competent for intracellular stimulus reception5 transduction and for subse/uent intercellular transmission. 2sseous mecanotransduction may involve the complementary process of: i)%echanical transduction. ii) 7onic transduction. i) %echanical transduction : 7t has been shown that a series of macromolecular mechanical levels e0ist$ which are capable of transmitting information from the strained matri0 to the bone cell nuclear membrane. This molecules is supposed to be physically continuous from the e0tracellular collagen matri0 to the intracellular cytoskeletal actin5 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) channels. 1) #oltage 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). 7onic transduction : 2steocytes may contain two types of ionic

;A

4)

'tretch activated ionic channels - 7n strained bone tissues and in fibroblasts too$ stretch activated channels e0ist. When active$ they permit passage of a certain si,ed ion.s) like *a 66$ K6$ a6 etc. 'uch ionic flow may modulate membrane potential and also to some e0tent regulate *a66 influ0 .Figure).

The other possible 7onic transduction mechanisms are: +) )lectric field strength - 4one responds to e0ogenous field strengths and there seems to be a parallel between these and endogenously produced fields by muscles. 3) )lectrokinetic - These are bound and unbound charges which e0ist in bone field.s) and are of streaming potential origin. These charges can initiate both osteoclastic and osteocytic action potentials. *onsiderations in %echanotransduction & %echanotransduction principle is based on the following factors: & & ormal skeletal muscle strains are attached intermittently. !ynamics of skeletal muscle contraction fit nicely with energetic re/uirements for bone cell responsiveness. o 4oth stimulatory and regulatory. & 4one cells may be stimulated directly via the channels or indirectly by electrokinetic phenomena.

;<

M4one seems to be 9tuned: to the skeletal muscleI .'keletal 8nits) "eriosteal %atri0. 1s %oss "uts it: 9When both ionic and mechanical transductive processes are conceptually and operationally combined with the data of both electric field effects and of contraction fre/uency energetics they provide a logically sufficient biophysical basis support for the hypothesis of epigenetic regulation of skeletal tissue adaptation:.

Bone as an Osseo.s )onne'ted )e Networ% 2))N4

1ll bone cells$ e0cept osteoclasts are e0tensively connected by gap @unctions. Gap @unctions are seen where the plasma membranes of markedly overlapping canalicular processes meet. These canaliculi are e0tensions of the osteocytes which lie in the bony matri0. The canalicular processes are seen to interconnect neighbouring cells processes. Gap @unctions also connect superficial osteocytes to periosteal and endosteal osteoblasts5 and vertically the periosteal osteoblasts with preosteoblastic cells. Gap @unctions are seen to permit movement of the ions$ small molecules and even the fluorescent dyes.

;=

They can be termed Melectrical synapsesI$ which permit bi&directional signal traffic. 4one tissue seems to be interconnected through layers as a network$ where parallel distributed signal processing occurs. The ** cells are organi,ed into layers$ the chief units being MinputI layer$ an output layer and a series of intermediate or MhiddenI layer.s). )ach 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. 'imilar 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.

E!i#eneti' !ro'ess o& oadin#

Coading as a process loading is un/uestionably of greatest importances at the clinically significant structural levels. Coading acts not only at the tissue levels$ but also at cellular and subcellular levels.

;E

The epigenetic mechanisms involved include: & Degulation of multicellular tissue morphogenesis - via e0tracellular matri0 and transduction. & *ontrolling osteoblastic gene e0pression through mechanical layers altering cell shape. 1t the tissue levels also$ epigenetic mechanisms have been noted for e0: in cartilage. 1t the organ level$ the vital role of articular function is well known. Reg)lation of periosteal matrices: & & %echanical loads - "henotype. eutrophism - Genotype.

New 1nsi#ht into the Ro e o& Periostea Matri'es(

*onsidering that the morphogenetic primacy of the periosteal matrices is accepted$ one can logically deduce the following: & "hysical loading tends to deform bone tissue and invoke the skeletal unit adaptive response. )0: temporalis. & %echanoreception occurs chiefly$ through some periosteal osteoblasts may be directly stimulated. & 'train is believed to be a competent stimulus and the attributes may vary with: o Type of loading. o Fine tuning.

;G

&

%echanotransduction$ either of ionic or mechanical nature occurs throughout the osseous ** .

&

2utput or the adaptive response is via the signals which get transduced through summation.

Evo .tion o& the )o"! e5ity Theory o& the 0MH
*omple0ity theory provides description of the behaviour of comple0 biologic systems which e0ist as MensemblesI and not as clusters of individual cells and e0tracellular substances. 7n this system a functional cranial unit is termed as *omple0 1daptive 'ystem .*1'): *omple0ity Theory .*T) involves processing of both genomic and epigenetic information by the *1'. 7t also implies that growth and development$ to a significant e0tent e0hibit 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 organi,ed processes and mechanisms. 'uch self organi,ing events can create phenotypic variability under genetic and epigenetic conditions. The operation of comple0it has been termed by him as 9)nvironmental factors thus play a decisive role. 4ut it is the organism itself that$ as an integrated system dictates the nature of each and every developmental response:.

;H

MThe living organism self organi,es on the basis of its own internal structuring$ in continuous interaction with the environment in which it finds itselfI. %oss has also compared between the genetic and epigenetic mechanisms. & (e rebukes the geneticists claim of high genetic control - odontogenic regulation by epigenesis. & & The genetic thesis is denied because it is reductionist and molecular. (e 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 e0trinsic .epigenetic) processes and mechanisms integrate and provide the necessary and sufficient causes of growth and development.

A>

Thesis 2Geneti'4

Antithesis 2E!i#eneti'4

Resolving !ynthesis

Comple:ity %heory

A+