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The Controversy continues...

Genomic theory goes directly from DNA to adult morphology, ignoring role of epigenetic mechanisms competent to control intervening and more complex developmental stages

Epigenetics refers to the entire series of interactions among cells and cell products, leading to morphogenesis. Thus, all cranial development is epigenetic, by definition.

Connected Cellular Network

  • Gap Junctions
  • Allow for intERcellular transmission (via ions)
  • CCN is nonmodular -the organizational variations permit discrete processing of different signals (the triad of histologic responses to one loading event)

Take Home Message

...sort of

Epigenetic Processes

Mechanical loads regulate skeletal muscle phenotype, and chronic muscle stimulation can change its phenotype.

Mechanical epigenetic factors (function) significantly control musculoskeletal growth, development, and maintenance of structural and physiological attributes

Function over form.

Nevertheless, epigenetic processes and events are the immediately proximate causes of development, and as such they are the primary agencies of growth and development

And the winner is...

Mechanical loading influences gene expression.

  • Musculoskeletal loading can change both articular cartilage intercellular synthesis and osteoblastic gene expression

Cell shape changes.

  • Tissue loading can alter cell shape, invoking mechanotransduction and a change in genomic regulatory signals.

a Tie...?

Orthodontic Implications

Genomic (formal cause) and Epigenetic (efficient cause) factors are both necessary.

Only the interactions of the two provide the necessary and sufficient cause of morphogenesis.

Functional appliances can alter the musculature, and therefore may lead to growth and development modification, which is VERY NICE for patients with skeletal malocclusions.

Path to Change

Bone adaptation

Bone closely "tuned" to Muscle

  • Extrinsic physical loadings tend to deform bone tissue and invoke bone adaptation responsive processes (example: coronoid process form by the temporalis)
  • Although no one mechanical parameter reliably predicts all bone adaptation and remodeling, STRAIN plays the primary role
  • Periosteal functional matrix loading event=muscle contraction

Epigenetic Event (Muscle Contraction)

Signals down through cellular and molecular levels to bone cell genome

Signals back up through histologic levels to the event of gross bone form adaptational changes

  • Muscle function strains attached bone tissue intermittently
  • Muscle contraction dynamics coincide with energetic requirements for bone cell response
  • Range of strain frequency of muscle dynamics found to be morphogenetically competent
  • Normal muscle activity produces electric fields similarly morphogenetic
  • Bone cells activated directly by strain activating plama membrane channels and indirectly by electokinetic phenomena

The Theory

Genomic Theory vs Epigenetic Theory

The cranial skeleton's growth and development is primarily dictated temporally and directionally by their related non-skeletal cells, tissues, and organs (ie the functional matrices)

Genomic hypothesis: the genome contains all the info needed to generate a diversity of cell types in the precise pattern of tissues and organs

Causation

Material (With what?)-Intrisic

Formal (by what rules?)- Intrinsic

Efficient (How?)- Extrinsic

Intrinsic vs Extrinsic

Genomic Antithesis

Epigenetic hypothesis: the outside environment influence the growth and development of an organism

  • revisions strongly support the primary role of function in craniofacial growth and development

Both intrinsic causes are prior, meaning they exist before the creation of some specific state or structure.

Efficient cause is proximate, meaning its operation immediately causes the creation of a new state or attribute

Includes all epigenetic factors!

or

Emergence- at each higher and more complex level, new attributes/properties arise whose existance could not be predicted from lower levels. Not Genetically Controlled

  • Full knowledge of properties of osteocytes does not permit prediction of any type of bone tissue

Genomic Thesis

  • Claims genes control developmental, physiological, psychological, and sociological events
  • only ~100 specific proteins, which create the differences in all cells
  • Deals with only the molecular level of structural organization

Claim of genomic control of molecular sytheses underlying the formation of skeletal tissue 'building blocks' does not substantiate the further claim that the genome regulates the growth and development of the gross anatomical bone.

  • Melvin Moss
  • 1962
  • Revisions in 1997

Epigenetic Odontogenesis

  • Chiclid (sic) fish=polyphyodont
  • Exhibit dental phenotypic plasticity
  • Tooth form is dependent on preceeding diet 'hardness'
  • epigenetic signals expression of genomic products
  • Epigenetic factors are the"Prior, proximate, extrinsic, and primary CAUSE of all adaptive, secondary responses of skeletal tissues" (Moss, 1997. AJODO Vol 112, No I)
  • The genome does not DIRECTLY regulate growth and development

Stimulus to Change

Periosteal Functional Matrix Stimulus

Signals (ionic or mechanical) hierarchically moves down to osteocytes

Leads to the regulation of the genomic activity of its strained skeletal unit bone cell, thus effecting phenotypic expression

Bones are Unique

Mechanotransduction

Mechanoreception-extracellular stimulus-->receptor cell

Mechanotransduction- transforms the content of the transmitted stimulus into an intRAcellular signal

Bone adaptation requires subsequent intERcellular signals

Bone cells are not specialized--can evoke multiple responses

aneural

bone adaptation confined within each bone independently (ie every bone for himself)

The Functional Matrix Hypothesis

Presentation by Katie Plunkett

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