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functional matrix theory and articles by melvin moss

1. AMERICAN JOURNAL OF ORTHODONTICS ,1969

2. Function In Head Functional Matrix Component Functional Matrix Skeletal Unit Growth change is secondary

3. SKELETAL UNIT BONE, CARTILAGE OR TENDINOUS ≠ “BONES” OF CLASSICAL TISSUE OSTEOLOGY Such a “Bone” No. of a skeletal unit MICRO SKELETAL UNIT No. of neighboring “bones” As a single cranial component MACRO SKELETAL UNIT

4. Micro skeleton unit of mandible Coronoid micro skeletal unit temporalis muscle Angular micro skeletal unit masseter and medial pterygoid muscles Alveolar micro skeletal unit presence and position of teeth Basal micro skeletal unit inferior alveolar neuro vascular triad Each micro skeleton unit is independent of each other

5. FUNCTIONAL MATRIX ( muscle, glands, nerves, vessels, fat) PERIOSTEAL MATRIX CAPSULAR MATRIX MATRIX Muscles, blood vessels, functioning space or organ Nerves, glands and teeth Produces Morphological cause expansion Changes In their skeletal Unit deposition and translation as a whole resorption of bone tissue

6. There exists confirmatory data which shows that experimental removal of the mammalian temporalis muscle or its denervation results in actual diminution of coronoid process size and shape or it’s total disappearance PERIOSTEAL MATRIX

7. Finally, it is ,established also that experimental or clinical alteration of the muscles attaching to the other mandibular ramal skeletal units can produce compensatory changes in temporalis muscle function. This will equally well change the size and shape of the coronoid process in proportion to the degree of muscular imbalance produced. Hypertrophy/ hyperactivity Increased Coronoid Of Temporalis size and shape

8. It is believed that the changes in size and/or shape brought about by deposition and resorption of bone tissue constitute the entire phenomenon of growth, then one is forced to the logical conclusion that the change in horizontal position of the mandibular ramus during growth is produced entirely as a result of such direct microskeletal unit tissue responses to periosteal matrices, be these tissues osseous or cartilaginous.

9. CAPSULAR MATRICES All skeletal units, and thus all bones in the formal sense, arise, exist, grow, are maintained, and respond morphologically while totally embedded within their functional periosteal matrices. At the same time, all these functional cranial components (functional matrices plus skeletal units) are organized in the form of cranial capsules .

10. Capsular matrix are of 2 types - 1) neurocranial capsule 2) orofacial capsule Each of these capsules is an envelope which contains a series of functional cranial components (skeletal units plus their related functional matrices)are sandwiched in between two covering layers. In the neurocranial capsule these covers consist of the skin and the dura mater, whereas in the orofacial capsule the skin and mucosa form these limiting layers. All spaces intervening between functional components themselves, and between them and the limits of the capsule, are filled with indifferent loose connective tissue.

11. Each capsule surrounds and protects a capsular functional matrix

12. Neurocranial matrices In the neurocranium, we are dealing with volume of neural mass. The expansion of this enclosed and protected capsular matrix volume is the primary event in the expansion of the neurocranial capsule. The response of the capsule, is to expand in a compensatory manner.

13. All of the included and enclosed functional cranial components, that is, the periosteal matrices and their microskeletal units, are then obligatorily carried outward within the capsule in a totally passive manner. The calvarial functional cranial components,are passively and secondarily translated in space without need of deposition and resorption and activity of periosteal matrices on their respective microskeletal units goes on simultaneously.

14. When we examine these pathologic, or experimentally produced, situations in which periosteal matrices have been prevented from exerting their morphogenetic activity, we can observe clearly the passive, nonperiosteal , translative growth produced by the capsular matrices. To conclude neurocranial capsule, the expansion of the neural mass is the primary event which causes the secondary and compensatory growth of the neural skull.

15. OROFACIAL MATRICES All functional cranial components of the facial skull arise, grow, and are maintained within an orofacial capsule This capsule surrounds and protects the oro - naso -pharyngeal functioning spaces. The volumetric growth of these spaces which is the primary morphogenetic event in facial skull growth.

16. The oral and pharyngeal region are said to have primary function in maintaining a patent airway. This is accomplished by a dynamic musculoskeletal postural balance which is termed the “airway-maintenance mechanism. ”

17. The bilateral removal of mandibular condylar cartilages, does not inhibit either the translation of the acondylar complex of mandibular functional cranial components; nor does it inhibit the changes in the form of their microskeletal units as their individual matrices alter their functional demands.

18. MANDIBULAR GROWTH Mandibular growth is seen now to be a combination of the morphologic effects of both capsular and periosteal matrices. The capsular matrix growth causes an expansion of the capsule as a whole. The enclosed and embedded macroskeletal unit accordingly, is passively and secondarily translated in space to successively new positions.

19. In normal conditions the periosteal matrices related to the constituent mandibular microskeletal units also respond to this volumetric expansion. Such an alteration in their position causes them to grow; that is, causes changes in their functional demands. These now call direct alterations in the size and shape of their microskeletal units. The sum of translation plus changes in form comprises the totality of mandibular growth.

20. Conclusion The origin, growth and maintenance of all skeletal tissues and organs are always secondary compensatory and obligatory responses to temporally and operationally prior events or processes that occur in specifically related nonskeletal tissues, organs or functioning spaces (functional matrices). Two basic types of such matrices-periosteal and capsular Periosteal matrices include muscles and teeth, and they act upon skeletal units by osseous deposition and resorption There net affect is to alter the form(size and shape) of their respective skeletal units.

21. The capsular matrices arc conceived of as volumes enclosed and protected by both the neurocranial(neural mass) and the orofacial capsules. Capsular matrices act upon functional cranial components as a whole in a secondary and indirect manner. They do so by altering the volume of the capsules within which the functional cranial components are embedded and they cause translation of cranial part. Cranial growth is a combination of the morphogenetically primary activity of both types of matrix. Growth is accomplished by both translation and changes in form.

22. AMERICAN JOURNAL OF ORTHODONTICS ,1997

23. Constraints of FMH 1. Methodological : FMH used only macroscopic measurement by using point mechanics and arbitrary reference frames like roentgenographic cephalometric radiographs permitting only method-specific descriptions that can not be structurally detailed. This constraint was overcome by using continuum mechanics techniques of the finite element method and of the related macro and boundary element methods. This method added quantitative aspects of localized cephalic growth kinematics to the earlier qualitative description of growth dynamics.

24. Hierarchical Constraint FMH does not explain how extrinsic , epigenetic functional matrix stimuli are transduced into regulatory signals at the cellular, and molecular levels.. The epigenetic could not explain or predict the higher attribute of the bone tissue. The new version of FMH tries to bridge the gap between hierarchical constraints and explains the operation from genome to organ level by two concepts: 1 . Mechanotransduction occurring in single cells . 2. That bone cells function multicellularly as a connected cellular network.

25. MECHANOTRANSDUCTION MECHANO: : relating to a mechanical source; mechanical TRANSDUCTION : any process  by which a biological cell converts one kind of signal or stimulus into another .

26. Osseous Mechanotransduction Static and dynamic loadings are continuously applied to bone tissues tending to deform both extracellular matrix and bone cells. When appropriate stimulus exceeds threshold values Loaded tissue responds by bone cell adaptation processes Osteocytes and osteoblasts are competent for intracellular stimulus reception and transduction and subsequent signal transmission.

27. The osseous mechanotransduction has four unique properties: 1. Bone cells are not cytologically specialized like other mechanosensory cells. 2. Single bone loading stimulus evokes three adaptational responses, whereas the non osseous process generally evokes one. 3. Osseous signal transmission is aneural ; it does not involve neural pathways, unlike other mechanosensory signals. 4. The adaptational response is confined within the individual bone organ independently.

28. Mechanotrasnductive processes 1. IONIC: brings about the transport of ions through the osteocytic plasma membrane resulting in the creation of an electrical signal. Stretch activated channels Loading S-A get activated Electrical processes:- These include several mechanotransductive processes:- Electromechanical, Electrokinetic and Electric field strength. Intracellular electric events passage of certain ion K+, Ca+ and Na+

29. ELECTROMECHANICAL :- Voltage-activated ion channels in the osteocytic plasma membrane hint at a mechanism for transmembrane ion flow, crucial for mechanotransduction . These flows might also trigger osteocytic action potentials transmitted through gap junctions. ELECTROKINETIC :- Bone tissue contains electric charges in its fluid, termed electrokinetic, generating streaming potential (SP) rather than piezoelectricity. SP measures strain-generated potential (SGP) from charge convection in deformed bone fluid flow. An SPG of +2 mV typically stimulates osteogenesis and osteocytic action potentials.

30. 3) ELECTRIC FIELD STRENGTH :- Bone responds to external electrical fields, possibly influenced by field strength, which correlates with muscle activity. Effective field strengths range from 1 to 10 μV /cm, resembling those during normal muscle activity.

31. 2. Mechanical process:- The basis of this mechanism is the physical continuity of the transmembrane molecule integrin. This molecule is connected extracellularly with the macromolecular collagen of the organic matrix and intracellularly with cytoskeletal actin. It is suggested that such a cytoskeletal lever chain can provide a physical stimulus able to activate the osteocytic genome.

32. 1997 American Journal Of Orthodontics and Dentofacial Orthopedics Aim:- To Consider The Implications Of The FMH And The Inclusion Of Connectionist Network Theory

33. BONE AS AN OSSEOUS CONNECTED CELLULAR NETWORK (CCN) All bones cells (except osteoclasts) are extensively interconnected by gap junction and form an osseous connective cellular network. Osteocytes have cytoplasmic processes which are oriented three dimensionally and are architecturally well-suited to sense deformation of the mineralized matrix.

34. GAP JUNCTION- are found where plasma membrane of pair of markedly overlapping cannicular process meet. Gap junctions connects:- Superficial osteocytes to periosteal and endosteal osteoblast Periosteal osteoblast with pre-osteoblastic cells and these in turn are similarly interconnected.

35. Gap junctions are electrical synapses , in contrast to interneuronal , chemical synapses. They permit bidirectional signal traffic, e.g., Biochemical, ionic. Mechanotransductively activated bone cells, e.g., Osteocytes, can initiate membrane action potentials capable of transmission through interconnecting gap junctions.

36. CCN is operationally analogous to an "artificial neural network, in which massively parallel or parallel-distributed signal processing occurs. In network theory, these cells are organized into "layers": an initial input, a final output, and one or more intermediate or "hidden" layers .

37. Initial cell layers- Osteocytes (mechanoreceptors) sense stimuli from periosteal functional matrix Summation of all the inputs Comparison & intercellular mechanotransduction hidden cell layers- (i.e. Adj. Osteocytes) propagation of action potential Final cell layer(osteoblasts) output

38. NETWORK THOERY Information is not stored discretely in a CCN, as it is in a conventional, single CPU computer. Rather it is distributed across all or part of the network, and several types of information may be stored simultaneously. The instantaneous state of a ccn is a property of the state of all its cells and of all their connections. Accordingly, the informational representation of CCN is redundant, assuring that the network is fault or error tolerant, i.E. , One or several inoperative cells causes little or no noticeable loss in network operations, which is a matter of useful clinical significance.

39. The ccns show oscillation, i.E. , Reciprocal signaling (feedback) between layers. This attribute enables them to adjustively self-organize This behavior is related to the fact that biologic ccns are not preprogrammed; rather they learn by unsupervised or epigenetic “training”. Gap junctions are electrical synapses that permit bidirectional flow of information, are the cytological basis for the oscillatory behavior of a ccn .

40. ATTRIBUTES OF CCN Developmentally, it is an untrained self-organized, self-adapting and epigenetically regulated system. Operationally, it is a stable, dynamic system that exhibits oscillatory behavior permitting feedback. Structurally, an osseous CCN is nonmodular, i.e., the variations in its organization permit discrete processing of differential signals. It is this attribute that permits the triad of histologic responses to a unitary loading event.

41. Strain probably plays the primary role and is a competent stimulus in bone remodeling responses. The significant strain attribute may vary with specific conditions. These include:- Loading category- Bone responds best to dynamic rather static loading. Frequency- Osteocytes may be physiologically "tuned" to the frequencies of muscle function. High order frequencies, significantly related to bone adaptational responses. Magnitude- Relatively small microstrains are morphogenetically competent.

42. CONCLUSION Where the original FMH version offered only verbal descriptions of periosteal matrix function and skeletal unit response, the addition to the FMH of the concepts of mechanotransduction and of computational bone biology offers an explanatory chain extending from the epigenetic event of skeletal muscle contraction, hierarchically downward, through the cellular and molecular levels to the bone cell genome, and then upward again, through histologic levels to the event of gross bone form adaptational changes.

43. AJODO,1997

44. •The initial version of the functional matrix hypothesis (FMH), claiming epigenetic control of morphogenesis, was based on macroscopic experimental, comparative, and clinical data. • Recently revised, it now extends hierarchically from gross to microscopic levels and identifies some epigenetic mechanisms capable of regulating genomic expression.

45. ODONTOGENIC EXAMPLE OF GENOMIC/EPIGENETIC DICHOTOMY

46. Because each dental replacement cycle involves identical odontogenic stages, it is postulated that: Mechanical forces, related to differential diet "hardness," generate epigenetic signals, mechanotransductively processed by dental papilla cells; and These signals control at least the temporal and spatial expression of genomic products related to the development of differential tooth form, such as size and shape.

47. THE GENOMIC THESIS The genomic thesis holds that the genome, from the moment of fertilization, contains all the information necessary to regulate (cause, control, direct) The intranuclear formation and transcription of mrna and all of the intracellular and intercellular processes of subsequent, and structurally more complex, cell, tissue, organ, and organismal morphogenesis

48. Therefore, morphogenesis is but the predetermined reading-out of an intrinsic and inherited genomic organismal blueprint For example, specific patterns of gene regulation cause, control, regulate, determine the mechanisms by which a fertilized egg divides and progresses through the various decision points to yield groups of cells that are first determined to become and then actually differentiate to become specialized tissues of the right dimension and in the proper location

49. Molecular (gene) genetics extended the claims of the thesis to the regulation of all aspects of ontogeny ( i.E. , Of "growth and development"). The mega-human genome project, explicitly intends to: Describe the complete human genome; Demonstrate genomic controls of all developmental processes, at all structural levels, from the subcellular to the organismal; In a societal context, possibly lead to some type of neoeugenics .

50. BIOLOGIC BASES FOR GENOMIC THESIS The somatic cells of an individual metazoan inherit two classes of molecular information: An identical diploid DNA and The maternal cytoplasmic constituents of the egg: e.g., Mitochondria, cytoskeleton, membranes. Only approximately 10% of the genome seems related to phenotypic ontogenesis, whereas, well over 90% does not encode precursors to mrnas or any other rna .

51. THE GENOMIC THESIS IN ORAFOCIAL BIOLOGY • There is extensive support for the genomic thesis in the orofacial biology literature, with most genetic studies of cephalic or cranial morphogenesis explicitly or implicitly assuming genomic regulation of each anatomical structure. • Prenatal craniofacial development is controlled by two interrelated, temporally sequential, processes: (1) initial regulatory (homeobox) gene activity. (2) subsequent activity of two regulatory molecular groups: Growth factor families and steroid/thyroid family.

52. • It is claimed that regulatory molecules can (1) "alter the manner in which homeobox genes coordinate cell migration and subsequent cell interactions that regulate growth" and (2) be involved in the "genetic variations causing, or contributing to, the abnormal development of relatively common craniofacial malformations. Orthodontic implications • poor co-ordination of form and size of structures(teeth and jaws) by regulatory genes result in malocclusion and dentofacial deformitites .

53. AJODO , 1997

54. EPIGENETIC ANTITHESIS • The epigenetic antithesis detailing the processes and mechanisms seeking to clarify the casual chain between genome & phenotype. • Process is a series of action or operation that had towards a particular result. • Mechanism is a fundamental physical or chemical process involved in, or responsible for an action, reaction or other nailed phenomenon.

55. Epigenetic process of loading - many different mechanism are capable of modifying phenotype. 1. Loads may act at - cellular level or tissue level 2. Loads may be – dynamic or Static 3. To be effective load may increase,decrease or remain constant Epigenetic mechanism at cellular level- Deformation of extracellular matrix. Altering the cell shape. Epigenetic regulation at higher level- Regulation of periosteal matrices.

56. A RESOLVING SYNTHESIS • It argues that morphogenesis is regulated by the activity of both genomic and epigenetic processes and mechanisms. • Both are necessary causes; neither alone are sufficient causes; and only their integrated activities provides the necessary and sufficient causes of growth and development. • Genomic factors are considered as intrinsic and prior causes; • epigenetic factors are considered as extrinsic and proximate causes.

57. Complex adaptive system Ensemble of several tissue and organs. Cas processes genomic and epigenetic information in parallel manner. Minor changes in epigenetic input result in huge fluctuation in morphogenetic output .

58. • Ontogeny is a nonlinear process. • Spontaneous self organising ontogenic processes and mechanism can create phenotypic variability under constant genetic and other extra organismal epigenetic condition.

59. • OPERATION OF COMPLEXITY can be suggested as- "environmental factors thus play a decisive role in all ontogenetic processes. But it is the organism itself that, as an integrated system, dictates the nature of each and every developmental response, the living organism self-organizes on the basis of its own internal structuring, in continuous interaction with the environment in which it finds itself.”

60. CONCLUSION Genomic and epigenetic processes are examples of totally differing types of causation genomic formal cause and epigenetic efficient cause. Individually both are necessary causes, but neither are sufficient causes alone. Together they provide both the necessary and sufficient causes for the control (regulation) of morphogenesis. Epigenetic processes and events are the immediately proximate causes of development, and as such they are the primary agencies.

61. SUMMARY

62. Functional cranial component SKELETAL UNIT FUNCTIONAL MATRIX MACROSKELETAL EX: MANDIBLE MAXILLA MICROSKELETAL Ex: coronoid, angular, alveolar,basal , Orbital, pneumatic, palatal , basal Periosteal ex: muscles, glands, nerves, vessels , fat Capsular ex: neurocranial , orofacial

63. Functional matrix hypothesis is a series of 4 articles given by melvin moss in 1997: 1- the role of mechanotransduction 2- the role of osseous connected cellular network 3- the genomic thesis 4- the epigenetic antithesis and resolving synthesis.

64. THE ROLE OF MECHANOTRANSDUCTION THE ROLE OF OSSEOUS CONNECTED CELLULAR NETWORK (1997) enable a cell to sense and To respond to extrinsic surrounding transmits extracellular physical Stimulus to receptor cell transforms stimulus information Into intracellular signal Loading static dynamic mechanosensing mechanoreception mechanotransduction

65. (Transmits information From strained matrix To bone cell nuclear Membrane) mechanotransduction Ionic/electrical mechanical Stretch activated channels Electro-mechanical electrokinetic Field strength Macromolecular level Skeletal signal growth CCN Response deposition resorption maintainance

66. THE GENOMIC THESIS (1997) The genomic thesis holds that the genome, contains all the information needed for growth and development of an organism from intrauterine life to senescence. This theory argue that all (phenotype) features are ultimately determined by dna sequence of genome.

67. THE EPIGENETIC ANTITHESIS AND THE RESOLVING SYNTHESIS (1997) Both the genomic (intrinsic, prior) and epigenetic (extrinsic, proximate) factors are each a necessary cause, but neither alone is a sufficient cause. Only the interaction of both provides both the necessary and sufficient cause of morphogenesis.

68. THANKYOU