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113 Cards in this Set

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Tooth Development Intro
-pay attention to the relationship between epithelial and mesenchymal cells
-teeth develop from the maxilla and mandibular process of the first pharyngeal arch at about 5 weeks
-At first tooth development is due to the oral epithelium, but after time the signal is sent from the ectomesenchyme
Primary Epithelial Band
-At 5 weeks the primary EPITHELIAL band forms in the arches and thickens (NCC derived)
-The dentition at this point is broken into 2 layers. The superficial layer is the oral epithelium (primary epithelial band) and the deep layer is the ectomesenchyme
-At 37 days a continuous band of thickened epithelium forms around the mouth at the jaws - future dental arch
-Grow is not due to increase proliferation, due to change in orientation of division so it's perpendicular to the surface
-The oral epithelium will receive a signal from the ectomesenchymal and grow into it forming the dental lamina
-Primary epithelial band becomes the dental and vestibular lamina
Dental and Vestibular Lamina
-The dental lamina is a epithelial outgrowth into the ectomesenchyme at the site of future teeth.
-Ectomesenchymal cells accumulate around the outgrows

-Vestibule is the section between the cheek and the tooth
-It forms due to proliferation of the vestibular lamina into the ectomesenchyme AFTER dental lamina formation. The enlarged vestibular lamina will degenerate and form a clef or open area
Development Stages overview
Primary Epithelial Band - 5 weeks
Bud Stage - 6-8 weeks (ingrowth)
Cap - 8-12 weeks (morphogenesis)
Bell - 12-16 weeks (differentiation)
Crown - 18 weeks - mineral forms
Bud Stage of Tooth Development
-Represented by first epithelial incursion into the ectomesenchyme
-Epithelial cells show little change in shape or function
-Ectomesenchymal cells pack closesly beneath and around the epithelial bud
Cap Stage
-As the epithelial bud divides into ectomesenchyme (EM), the bud splits into a cap-like structure. Also, the EM density around the bud increases due to condensation
-The condensed EM are called the dental papilla (dentin and pulp) and the bud at this point is the enamel organ
-The area around the dental papilla and enamel organ is the dental follicle/sac (supporting tooth)
-The enamel organ, dental papilla, and dental follicle constitute of the dental organ or tooth germ
-The cells in the center of the enamel organ are the stellate reticulum. They secrete GAGs which pull water into the enamel organ. The water increases volume of the EC compartment and forces the cells apart into a star shape maintained by desmosomal contacts
Enamel Knot
-A cluster of nondividing epithelial cells around the inner enamel epithelium where the cusp will be
-Each tooth germ has a single primary enamel knot at the cap stage, and as these disappear, secondary enamel knots appear at the tips of the future cusps in molars
-Enamel knot dies by apoptosis
-Expresses FGF-4, one knot for each cusp
-Enamel knot probably represents the organizational center for cuspal morphogenesis
Bell Stage (1) - Overview and Cells
-During this stage the tooth crown assumes its final shape, undersurface of the enamel organ deepends, and the ameloblast and odontoblast aquire their distinct phenotypes (cellular histodifferentiation)
4 main cell types in the enamel organ
1) Outer Enamel Epithelium - Organ periphery, cubodial, held by junctional complexes
2) Inner Dental Epithelium - Border the dental papilla, are short and columnar, and have high glycogen
-The inner and outer enamel epithelium are continuous at the cervical loop. This is where the epithelium begins to bend into the dental papilla area. This is also where cells continue to divide until the tooth crown attains its full size and gives rise to the epithelial components of root formation
3)Stellate Reticulum - held to intermedium and outer by desmosomes
4) Stratum Intermedium - Next to the inner enamel epithelium, these are several flattened layers. Although histologically distinct, these cells work with the inner enamel epithelium to form the enamel. Held to stellate and inner epithelium by desmosomes
Bell Stage (2) - Random
-Dental papilla is separated from the enamel organ by a basal lamina and a acellular zone where the first enamel matrix proteins are secreted
-The dental papilla is the tooth pulp when the calcified matrix appears
-The dental follicle is distinguished by many more collagne fibers
Bell Stage (3) - Breakup of Dental Lamina and Crown Pattern Formation
-Two important events occur during bell stage
1) Dental lamina disintegrates separating the developing tooth from the oral epithelium (why inner enamel epithelium need so much glycogen)
2) Inner Enamel Epithelium (IEE) completes its folding forming the future crown pattern
-This folding occurs as a result from intrinsic growth caused by different rates of mitotic division within the IEE
-From cap-to-bell the tooth germ grows rapidly. During the bell stage division stops at enamel knot because the cells begin to differentiate and form enamel (this is where the cusps will be)
-Because the IEE is constrained between the cervical loop and cusp tip, a stoppage of proliferation at the cusp tip, and a continuation of proliferation towards the cervical loop, causes the IEE to buckle and form a cuspal outline. The future cusp is pushed up toward the OEE
-The change from proliferation-to-differentiation in the IEE and dental papilla begins at the cusp tip and sweeps down along the cusp (to the CEJ) and is followed by desposition of dentin and enamel.
-During this process the stellate reticulum is reduced in thickeness at locations of mineral formation because mineralized enamel may block off nutrients to these cells
IDE/DP Junction
-At the cells begin to differentiate in the cap stage a number of events occur
1) IDE stop proliferating and send a signal to the dental papilla
2) Cell morphogenesis occurs so the IDE and DP becomes columnar and differentiate to pre-ameloblast and odontoblast. Also, there is a reference in polarity as the nuclei migrate in opposite directions away from the basement membrane
4) Odontoblast first secrete non-mineralized pre-dentin. When pre-dentin becomes mineralized the ameloblast will secrete enamel proteins
5) The basement membrane is transformed to the DEJ
Formation of Permanent Dentition
-All teeth go through same basic steps during tooth development, but timing differs
-Tooth germs that give rise to the permanent incisor/canine/premolar form as a result of further proliferative activity within the dental lamina at its deepest surface
-The molars originate in a unique way. When the jaw has grown long enough, the dental lamina borrows posteriorly beneath the oral mucosa epithelium and the ectomesenchyme
-This backward extension successively gives off epithelial outgrowths to form the 1st, 2nd, and 3rd molars
-Primary dentition starts between 6-8 weeks, permanent teeth between 20th week in utero and 10 month after birth, and permanent molars between 20th week in utero and 5 year of life
Summary of the Epithelial/Mesenchymal Interactions in Tooth Development
-These interactions and the timing are crucial for development and involve cells secreting proteins which binds other cells receptors, and often the signals are reciprocal
-Signal is important to determine tooth location. Example is Pax9, a TF
-The oral ectoderm secretes FGF8. When the EM receives this signal it makes PAX9 which changes gene expression allowing tooth development to occur. The cells around the tooth that make FGF8 and BMP4 do not get Pax9 expression and tooth formation
-Tooth development depends on the FGF8 gradient and a inhibition of Pax9 by BMP4
Hard Tissue Formation
-At the late cap early bell stage the cells stop dividing and undergo differentiation
-The ectomesenchyme at the cusp tip differentiate to odontoblast and first secrete unmineralized dentin, followed by the pre-ameloblast secreting their matrix. Continues from the cusp tip to the cervical junction
-The process of continued mineralization between odonto- and pre-amelo- is reciprocal induction. They need each other
-As the odonto- and pre-amelo reverse polarity and secrete proteins, the acellular zone disappears
-Dentin formation cuts off nutrition for the pre-ameloblast (IDE). Nutrients come from a collapse in the stellate reticulum and invagination of the outer enamel epithelium by blood vessels
-As the enamel and dentin form, the enamel organ will thin. This is called reduced enamel epithelium
Root Formation
-So far we have covered crown mineralization, but how does root dentin form?
-Epithelial cells of the inner/outer enamel epithelium proliferate from the cervical loop to form a double layer Hertwig's epithelial root sheath. The shealth is a continuation of the reduced enamel epithelium
-This layer will extend around the dental pulp within the follicle and the apical surface will become the primary apical foramen or epithelial diaphragm
-As the Hertwig sheath is formed, it will will not become ameloblast but will secrete enamel products that help ectomesenchyme cells to differentiate to odontoblast of the root
-As the root forms, the crown grows away from the tooth base and this stretches the root sheath cells. As the stretching continues the sheath will fragment to form clusters of epithelial cells called the cell rests of Malassez
-The rests of Malassez remain through adult life within the periodontal ligament
Formation of Supporting Tissue
-During the cap stage the supporting tissues of the tooth form from the fibrocellular dental follicle layer
-As the shealth's fragment, the dental follicle cells migrate between the epithelium, contact the dentin, and differentiate into cementoblast
-These cells make a organic matrix with mineralizaes and anchors collagen fiber bundles of the PDL
-In all the dental follicle contributes to cementoblast, periodontal ligament fibroblast, and alveolar bone osteoblast
-Cementocytes are trapped in cementum and have extensions called caniculi towards the PDL. This tissue thickens with age
Tooth Eruption
-Movement of the tooth from the alveolar development site to a functional position in the oral cavity
1) Bone Remodeling - Bone is remodeled to create a pathway for eruption (over the crown)
2) Root Growth
3) Mucosal Penetration - Penetrate the oral mucosa. As eruption begins the reduced enamel epithelium and oral epithelium fuse to form a solid mass of epithelial cells. These cells secrete proteases to make the central canal in this mass degenerate allowing the crown to erupt
4) Preocclusal Eruption - Until the occlusal plane is reached
5) PDL Remodeling - To permit movement
Eruption Timing
Incisor
Primary - mineral begins at 14 weeks pre-birth, crown complete at 1.5 months, and root at 2 yrs 9 months
Secondary - mineral begins at 3-4 months, crown complete at 3.5 yrs, root complete at 9 yrs
Secondary Eruption of Permanent Teeth
-Before permanent tooth erupts the primary tooth has its root absorbed by odontoclast - basically osteoclast, come through blood, fuse at tooth to make multinucleated cell, have ruffled border and resorption lacunae
-When the primary tooth comes out it is mostly enamel
-The PDL fibroblast will absorb the collagen in the PDL during tooth eruption and movement
Regulation of Eruption
-Three main factors, signal between the ectomesenchyme and the epithelial cells, the direction of the signal, and the timing of the signal
1) Signals - Signals from the dental follicle causes bone resorption above the tooth and bone formation below the tooth creating a pathway to push the tooth up
-The reduced dental epithelium above the tooth secretes a upward signal of TGF-B towards the dental follicle. This causes the DF to secrete CSF-1 which attracts monocytes to differentiate to osteoclast and degrade bone above the tooth to make a pathway
-At the same time cells below the tooth make RUNX-2 and osteoblast differentiate to make bone for the roots below the tooth to help eruption
2) Reciprocal interactions between the epithelium and mesenchyme allow for tooth formation
-Exps. done where skin and tooth epithelial and mesenchyme recombined. When skin mesenchyme and dental epithelium combined, skin was formed. When dental mesenchyme and skin epithelium added, a tooth was formed.
-Additionally, this relation determines the tooth shape. Incisor mesenchyme added to molar epithelium gives us a incosr
3) Timing - Which layer gives the signal constantly changes. First the epithelium is important, then the mesenchyme, then the epithelium, and this continues 20 times or so
Eruption Sequence
-Mandibular central incisor
-humans have heterodont dentition (different teeth)
-humans have diphyodont dentition or 2 sets of teeth (primary and permanent)
-Anodontia - A disorder where someone is missing teeth
-3rd molars, max lateral incisors, and mandibular 2nd premolars are most affected
-Oligodontia is where many teeth are missing
-Hypodontia - only a few teeth missing
Enamel Introduction
-Amelogenesis is the process of enamel formation
-Epithelial tissue that is very mineralized (hardest body tissue) and has almost no organic matrix (no collagen)
-Enamel mineral and proteins appear together so no pre-enamel
Enamel Early Development
Presecretory Phase
1) Late Bell Stage - Shape of crown determined by IDE which are cubodial and have nucleus centrally located
2) Early Crown Stage - IDE stop dividing, become columnar and polarized with their nucleus towards the cusp. Organelle (golgi, rER) increase in size and migrate towards dentin
Secretory Stage (1) - Starting and Tomes
-Starts after first dentin is secreted
-Ameloblast begin to migrate away from the dentin they form tomes process
-At first initial enamel is secreted near the dentin without any process
-As the ameloblast moves away from the dentin it will secrete secretory granules (with enamel proteins) to the proximal and then distal tomes process
-The proximal tones process is not in contact with the already formed enamel and creates interrods. The distal tomes is embedded in the enamel and forms rods
-Proximal portion extends from the end of the ameloblast cell body to the enamel layer surface, and the distal portion penetrates into the enamel
-Secretory granules go to 2 sites
1) Proximal tomes that form interrod enamel partitions, and these are continuous between ameloblast
2) Distal tomes that forms enamel tod which fill the enamel partitions. Interrod is ALWAYS first laid down before enamel rod
-At both interrod enamel and enamel rods the enamel is identical composition the only difference is orientation
Secretory Stage (2)
-Where most of the enamel matrix is produced
-As the distal tomes lengthens during enamel thickening it becomes thinner and eventually presses against the interrod cavity wall forming a narrow space between the rod and interrod that fills with organic material. This is the rod sheath
-Eventually as the enamel layer is laid down the ameloblast will become shorter and lose their tomes process.
-Because rod form in relation to the distal tomes, the final few enamel increments do not have rods, this is final enamel
-Enamel is thus composed of a rod-containing layer sandwiched between thin rodless initial and final layers
Enamel Formation Overview
1) Morphogenetic Stage (IDE) - Short
2) Histodifferentiation (reverse polarity) - Tall
3) Initial Secretory Stage - initial enamel without Tomes process - Taller
4) Secretory Stage with Tomes process - Tallest
5) Ruffle-ended ameloblast of the maturative stage - Additional mineralization - Shorter
6) Smooth-ended ameloblast of the maturative stage - Organic degredation and water absorption - Equally Short
7) Protective Stage - Ameloblast remain on surface to protect enamel - As short as stage 1
Transition Stage
-After full thickness of immature enamel (enamel matirx) forms many ameloblast undergo apoptosis
-Additionally the remaining cells shorten and excess organelles are digested
Maturation Stage
-Where the majority of the mineralization occurs and organic material is removed
-Ameloblast secrete a basal lamina rich in carbohydrates and amelotin and attach by hemidesmosomes
-In the maturation state they undergo modulation, consistently changing cell cycles between a ruffled-border and smooth-border
1) Ruffle Border - When ameloblast transport calcium and phosphate to the enamel
2) Smooth - Secrete proteates to digest organic proteins and engulf these and remove water
-As mineralized enamel forms the dental organ compresses and stellate reticulum disappears. The remaining layers of the enamel organ form the reduced dental epithelium
Enamel Proteins
1) Amelogenin - Hydrophobic and aggregate to nanosphere to help regulate crystal growth and enamel thickeness. Many isotypes. 90% of the enamel proteins. Must be removed for thickening.
-After C-teleopeptide is cleaved these form nanosphere and associate with HAP crystallites controlling growth and orientation. As the crystal grows these proteins are continuously cleaved leaving TRAP polypeptides
2) Non-Amelogenins - 10% of the secretory proteins. Short lived in enamel
a) Enamelin - Starts mineralization (crystal nucleation), acidic, and found at the DEJ
b) Ameloblastin - Found in rod sheath, helps hold the ameloblast to the matrix, and signals to HERS
c) Tuftelin - Found in enamel tufts

-It seems that enamelin initially helps nucleate CAP at the DEJ. After this is established the amelogenins help the continued elongation and orientation
Clinical Considerations
- Scientist found enamel-like material deposited by HERS during root formation
-They extracted a pig enamel protein in a vehicle called Emdogain
-When this is added to a root surface it leads to regeneration of cementum, PDL, and alveolar bone
-Active incredient is still not known but it is 90% amelogenin
Hydroxyapatite Overview
-Smallest unit is a unit cell which is Ca10, PO4(6)OH(2)
-Look like a hexogone around the star of david with OH in the middle
-Unit cells stack for form repeating unit of the lattice
-Fluoride can be substituted for OH which makes the crystal less soluble and more perfect. CO2 and Mg have the opposite effect
-Depending on the molecules present enamel will take different shapes but it is usually a hexagon
Notes Overview of Enamel Formation
-first dentin made
-then structurless enamel made with no rods and without any matrix granules. Before Tomes process no enamel rods, and enamel forms by interacting with dentin or independently
-enamel rods made when tomes process arise. At this point secretory granules release proteins which fuse3 with the cell membrane and release by exocytosis
-Rod sheaths are a space created by the crystal orientation at right angles (interrod and rod). Small amount of proteins are here
-THIS IS IMPORTANT - accoridng to the lecturer, Tomes process ONLY refers to distal Tomes which makes rods. Interrods are made by the ameloblast body, not proximal Tomes
Cross Striations
Because human enamel forms at 4 microns per day, within the enamel rods are periodic bands or cross striations at 4 microns
-May be artifact
Striae of Retzius
-In a longitudinal section they are dark lines extending from DEJ to tooth surface where they are called perikymata
-Due to variation in secretory activity or illusions. May be developmental lines
-Retzius are linear along the enamel sides but at the cusps they are circular in their pattern
Lamellae
-Faults in enamel mineralization where the mineralization was incomplete
-There is probably organic material here
Enamel Tufts and Spindles
Tufts - Extend from DEJ into the enamel and are feather-like structures that contain tuftelin
Spindles - Forms from the ends of odontoblast reaching into the enamel. Not featherlike, only 1 process
-The DEJ is usually scalloped in appearance
Hunter-Schreger Bands
-These bands are an optical phenomenon due to differences in direction of secretion of enamel rods by groups of ameloblast
-They are usually on the sides of enamel and apparent when enamel viewed by incident light
Changes in Enamel
1) Age - Enamel becomes worn, discolored, and loses permeability
2) Fluoride - Fluoride replaced the OH ion and makes enamel more crystalline, less permeabile, and more resilent to caries. However, too much fluoride leads to fluorosis where you see brown discoloration and structure problems on the fluoride
3) Illness - When the enamel is developing illness can cause a distinctive band of malformed enamel. When the disease goes away normal enamel formation continues
Dentin Overview
-Forms the bulk of the tooth
-Bone like matrix with collagen and hydroxyapatite, elastic properties (prevent enamel fracture), and dentin laid down by odontoblast
-The matrix is 45% HAP and 55% organic with collagen, noncollagen proteins (NCP), lipids, and water
-Col I acts as a scaffold for HAP and NCP regulate carbonated HAP mineralization
Types of Dentin
1) Primary dentin, including circumpulpal and mantle is the bulk of the tooth - Dentin that outlines the pulp chamber
2) Secondary dentin is continuously laid down by odontoblast - next to pulp. It is after root formation and deposited slowly
3) Tertiary dentin or reparative is laid down in response to a stimuli (restoration, caries, etc) - next to pulp or in pulp chamber
Dentin Formation
-Starts during early bell stage by odontoblast which differentiate from ectomesenchymal cells from the dental papilla
-Starts at the cusps (coronal dentin) and spread to the roots later
-Odontogenesis is the formation of odontoblast whereas dentinogenesis is the formation of dentin
Odontogenesis
1) In the dental papilla there are ectomesenchymal cells
2) The ectomesenchymal cell will divide
3) While the parent remains undifferentiated with stem cell properties, the daughter is influenced by the IDE to differentiate to a odontoblast
-The daughter cell will polarize the nucleus, elongate, and begin to laid down the dentin matrix (collagen first) at the DEJ basement membrane
Mantle Secretion (Predentin) and Globular Nucleation
1) Odontoblast secrete smaller collagen I and large fibronectin associated with collagen III (von Korff's fibers) to form the dentin organic matrix known as Mantle Predentin
2) Once the organic matrix is laid down the odontoblast will secrete matrix vesicles. Matrix vesicles will begin to mineralization, then the mineralization will continue outside the vesicle, and eventually the minerals will fuse
-After mineral seeding, NCP help regulate mineral desposition
-This is how coronal mantle dentin is made, and it is an example of globular calcification
-It is 20 microns thick and 4% less mineralized than circumpulpal dentin
Heterogenous or Linear Nucleation
-Contrary to globular calcification, is heterogenous nucleation
-Collagen molecules are staggered and spaced 67 nm. Nucleation occurs in the hole where the overlap is
-OBP (process) secrete NCP which assist mineralization by going in the holes
-DPP is acidic and heavily binds Ca
-Other NCP are DSP, DGP, DMP=1. and OPN
-This process is slower than globular calcification, so it is linear calcification
-Circumpulpal dentin shows both globular and linear calcification
Dentin Physical Properties
-highly elastic and softer to enamel. Provides support and flexibility to brittle enamel
Intertubular Dentin is similar to bone. It is softer than enamel but toughter
Peritubular dentin is between the 2, harder than interutbular but not as tough most likely
Dentin mineral has less calcium and more carbonate so it is less mineralized and more soluble - caries go through it faster than enamel
Odontoblast Process and Dentin Tubules
-Odontoblast start off short and cubodial but will grow to be columnar with lots of Golgi/rER at the basement membrane end. They will develop a OB-Process. Eventually the organelles will disappear and it will become cubodial again, but unlike ameloblast they do not necessarily die
-As the OB travels to pulp the process is left behind in the ECM. This creates a dentin tubule
-Each OB has 1 OBP that goes from the pulp to the DEJ
-The Process is S shaped and larger near the pulp.
-The process make dentin very permeable to caries
-Tubule direction changes at primary and secondary dentin
Predentin
-Predentin is the newly synthesized organic matrix that is near the odontoblast and unmineralized. Filled with collagen and proteoglycans (inhibit mineralization)
Circumpulpal Dentin
-The majority of primary dentin and forms after the mantle dentin
-It has increased mineral content due to the heterogenous mineralization
-The majority of proteins are collagen I fibrils parallel to the DEJ
-Composed of intertubular and peritubular dentin
Intertubular vs. Peritubular Dentin
1) Intertubular
-Located between dentin tubules (OBPs) and less mineralized than peritubular dentin
-Contains CAP, Col I, phosphoproteins, proteoglycans, and water

2) Peritubular Dentin
-Right around the dentin tubules. It is 40% more mineralized than intertubular dentin and contains less collagen (more mineral contains less collagen)
-Peritubular dentin helps protect the tubule and pulp chamber from caries
Physical Dentin Structures (1)
1) Incremental Growth Lines - The dentin organic matrix is deposited at 4 microns per day. Additionally, the daily increment is a 5 day cycle in which changes in the collagen fiber orientation are more exaggerated. These lines run at right angles to the dentin tubules forming the incremental lines of von ebner which are 20 microns apart. Run from the pulp to the DEJ. Cannot see with naked eye

2) Contour Lines of Owen - These are caused by periods of accentuated hypomineralization. Examples are illness and the period during birth (neonatal line - one of the biggest). They are exceptionally wide and incremental and can be seen with the naked eye
Physical Dentin Structures (2)
3) Interglobular Dentin - Areas of hypomineralization within globular zones of mineralization. Occur right below mantle dentin, in circumpulpal dentin which is very globular. Tubules pass through but no peritubular dentin in these areas

4) Tomes' Granular Layer - Seen just below the cementun of the root dentin. A progressive increase in so-called granules occurs from the CEJ to the tooth apex. The origin is controversial

5) Sclerotic Dentin - Dentin tubules in the same area that become occluded with calcified material. They become glassy and translucent. Amount of sclerotic dentin increases with age and reduces the permeability of dentin
Dentin-Enamel Junction
-This area is scalloped and has a narrow width and combines two dissimilar calcified tissues
- Mantle dentin and initial modified enamel
-Collagen fibrils and odontoblast processes span the width
-It is crack arresting and fracture resistant (cracks stop at dentin)
-Enamel has a greater hardness and E-modulus than dentin
Dentin Pain and Sensitivity
-The pulp is richly innervated and through 3 mechanisms the dentin can act as a nerve receptor and stimulate pain
1) Dentin contains nerve ending between the OBP and peritubular dentin. The nerves will respond to stimuli and transmit pain
2) Odontoblast serve as receptors coupled to nerves in pulp. A signal will start in the OBP and transmit to the nerve coupled to the OB cell body
3) Tubules permit fluid movement which is registered by a nerve ending near the odontoblast (hydrodynamic). Basically the fluid OB is moved in response to stimuli and this pushes and excites a nerve
Dentin in the Clinic
1) Enamel vs. Dentin Caries- caries progress much faster in dentin because it is only 50% mineralized compared with 90% enamel. Root caries with a thin layer of cementum over dentin progress faster than coronal caries with enamel

2) Restoring/Bonding to Dentin - acid-etch removes a layer and and increases the porosity of the exposed surface. It exposes collagen and NCP which can more easily adhere to the composite
Abnormal Dentin
1) Scurvy - Caused by a lack in vitamin C it causes weakness, anemia, gingivitis, and skin hemoorhages

2) Dentin Dysplasia (dentinogenesis imperfecta) - Is a genetic disorder showing opalescent, gray, yellow, or brown dentin. It is successptible to many enamel fractures, and the dentin undergoes rapid attrition (gradual reduce of strength or resistances, gradually wearing away)
-Due to osteogenesis imperfecta (bad collagen) or a problem with the DSPP gene
Dental Pulp Overview
-originate from the dental papilla that becomes pulp as the roots form
-It is a soft CT that supports dentin
-Think of pulp as a CT with fibroblast, blood vessels, nerves, and a ECM rich in collagen (undifferentiated cells of the dental papilla become fibroblast)
-Within the pulp there are 4 layers: odontoblastic zone, a cell free zone of Weil, a cell-rich zone, and the pulp core with the nerves and BV
Dental Pulp Overview (2)
-Because of the rigidity of dentin/enamel, the pulp is in a low compliance environment where it is easy for pressure and force to disrupt it
-Careful regulation of blood flow because vasodilation is limited
-The pulp is a unique sensory organ, sensitive to hot and cold.
-There is a interplay between nerves, BV, and the immune system
-The pulp has stem cells that form new odontoblast when dentin is needed, and this make reparative dentin throughout life
-
Cellular Zone of Pulp
1) Cell free zone of Weil - Beneath the odontoblast layer in the coronal pulp (not radicular or root pulp). Contains cell process (nerves and BV) but no cell bodies

2) Cell-rich zone has fibroblast, macrophages, and lymphocytes
Cells of the Pulp
1) Odontoblast - Line the pulp cavity. When they are quiescent they have little cytoplasm, while when they are synthetic (secretory) they have tons of organelles.

2) Fibroblast - The principle cell type in pulp, it secretes collagen and maintains the pulp matrix. Throughout life it produces/degrades collagen which is fine and haphazard when young, and large and bundled when old
-young fibroblast have lots of golgi because they need to process the collagen

3) Dendritic Cells - Help capture foreign antigens (come in through dentin tubules) and present to T-cells. Very numerous in the odontoblast layer where the Ags enter

4) Macrophages - Remove particulate matter and dead cells
Vascular Supply
-Pulp has arterioles, venules, and capillaries. NO veins or arteries
-Capillaries are under OB initially. As the OB transition to the secretory phase and make dentin and move backward, the capillaries become trapped around the odontoblast (continue to provide nutrients)
Pulp Lymphatics
-Lymphatics in pulp are in communication with the EC environment through the apical foramen and move tissue fluid
-Help maintain low compliance environment of the pulp
-Have discontinuous walls and no RBC
Pulp Nerves
-Pulp has both myelinated and nommyelinated nerves that enter through the apical foramen
-Axons in the cell-free zone are called the Plexus of Raschkow. These axons interact with the dentin tubules for sensation
-The myelinated axons lose their myelin near the dentin border so more and more nerves become unmyelinated at that point
-Collection of nerve bundles before the plexus of Raschkow is the trunk of Raschkow
-myelinated nerves are associated with sharp pain
-Nonmyelinated C fibers are associated with dull and diffuse pain

3 theories of pain in dental procedures are the 3 ways OB interact with nerves
-OB have sodium channels and can generate a action potential.
-Sensitivity has no evolutionary benefit
-Sensitivity is secondary to the pulpal roles of homeostasis and defense
Types of Dentin
Tertiary
1) Reactionary 3rd Dentin - Made by OB that survive an insult
2) Reparative - Made by newly recruited cells. This dentin is poor in phosphoproteins so these reparative OB may not fully differentiate
-Growth factors released from dentin during caries/insult trigger replacement OB proliferation. Dentin is not inert
Clinical Thoughts
1) Dead Tracts - When OB die it retracts its process from the dentin tubule. Allow for bacteria to enter

2) Calcification - Forms around BV, dead cells, and collagen fibers.
-Calcification in pulp is often pulp stones. They are calcified like dentin and have concentric layers of mineralized tissue.
-If pulp stone has tubules and cells (OB) it is true stone, w/o cells it is false stone
-If it is surrounded by soft tissue it is a free stone. If it attaches to the dentin or is surrounded by secondary dentin it is a attached sonte
-Pulp stones reduce total number of cells in pulp and cause problems during root canal therapy (enlarge is disrupt the canal)
Pulp and Age
-Pulp volume decreases with age due to continued deposition of dentin
-With age comes a loss of nerves so there is less sensitivity
-With age you get dystrophic calcification which generally originates in relation to blood vessels or as diffuse mineral deposits along collagen
Pulp Tissue Regeneration
Regeneration - complete restoration of tissue architexture
Repair - Function and continuity is restored, but the original architecture is distorted
-Stem cells are within the pulp
Tissue Engineering Overview
Definition - Science of Developing techniques for the fabrication of new tissue to replace damaged tissue
-requires cells, signaling molecules, and a scaffold
Nanotechnology - science of bioengineeringatr the molecular level to produce new materials with new properties - biodegradable scaffolds or scaffolds with instructional molecular messengers within them
Tissue Engineering Relation to Dentistry
1) Targeted Gene Therapy - insertion of a gene into cells to deliver proteins at therapeutic levels over a period of time
-In Sjogren's syndrome (low salivary gland production) you could insert cells to increase the flow. In the syndrome the cells last IL-10. So take the host cell, add IL-10 transgene, and put the modified cell back
Regeneration of Oral Tissue
Enamel: Ameloblasts are not present in adults so enamel cannot be biologically repaired

Dentin - Repairs itself naturally

Salivary Gland - Gene transfer therapy possible through excretory ducts
Pulp Tissue Regeneration
Regeneration - complete restoration of tissue architexture
Repair - Function and continuity is restored, but the original architecture is distorted
-Stem cells are within the pulp
Tissue Engineering Overview
Definition - Science of Developing techniques for the fabrication of new tissue to replace damaged tissue
-requires cells, signaling molecules, and a scaffold
Nanotechnology - science of bioengineeringatr the molecular level to produce new materials with new properties - biodegradable scaffolds or scaffolds with instructional molecular messengers within them
Tissue Engineering Relation to Dentistry
1) Targeted Gene Therapy - insertion of a gene into cells to deliver proteins at therapeutic levels over a period of time
-In Sjogren's syndrome (low salivary gland production) you could insert cells to increase the flow. In the syndrome the cells last IL-10. So take the host cell, add IL-10 transgene, and put the modified cell back
Regeneration of Oral Tissue
Enamel: Ameloblasts are not present in adults so enamel cannot be biologically repaired

Dentin - Repairs itself naturally

Salivary Gland - Gene transfer therapy possible through excretory ducts
Periodontium Overview
-The periodontium is a collection of tissues that hold and support the teeth
-Include the gingiva, alveolar bone, cementum, and periodontal ligament
-The attachment apparatus of cementum, periodontal ligament, and alveolar bone holds the tooth in the socket
-Different bacteria cause periodontitis and decay. Some people are more resistant. You can have one without the other
-Without the PDL you cannot move the tooth. So even a implant which has no cementum will not allow tooth movement
Structures of the Periodontium
1) Interdental Papilla - This is the gingiva between the teeth (triangle). Good for aesthetics. It is composed of gingiva. The shape is a pyramid on the anterior teeth, on the posterior teeth it forms a gingival col

2) Frenum - Hold the lip to the gums. No problem if it's removed. One on the upper and lower lip

3) Gingiva - Same thing as the masticatory mucosa. Is is directly around the crown of the tooth and cannot be moved. It is pink in color and heavily keratinized but does not have elastic fibers. It is a epithelial tissue

4) Alveolar Mucosa - Surrounds the alveolar bone (process). It is not keratinized, has many elastic fibers, dull in appearence, and can be moved. It is also considered epithelium. It is a thin tissue and injections do not hurt

5) Mucogingival Junction - Separated the masticatory mucosa (gingiva) and alveolar mucosa
Structures of the Periodontium (2)
6) Palatal Mucosa - Soft tissue that covers the hard palate. It is similar to gingiva and does not contain any alveolar mucosa. The skin here is tight to bone so injections can be painful
Gingiva in Details
-composed of 4 tissues, the oral epithelium, the sulcular epithelium, the junctional epithelium, and the gingival connective tissue
-Attached gingiva is the OE while free gingiva is the JE, SE, and marginal groove

1. GCT - The deep gingival tissue layer (kind of like the dermis in skin) which is in contact with the other 3 layers.
2. Oral Epithelium (OE) - Runs from the MGJ to the GM. It is covered in saliva and it is what you see in a healthy mouth
3. Sulcular Epithelium (SE) - Very small portion, it is where the OE turns into the sulcus.
-The sulcus is bordered by the tooth, the junctional epithelium (JE), and the SE. It has gingival crevicular fluid which has different proteins than saliva and it has both microbial and host cells

4) Junction Epithelium - Helps connect gingiva to the tooth. It is pushed down on by the perioprobe (measures depth of the clinical sulcus). Histological sulcus is something else
Variations in Gingiva
-The gingiva between people is very different
-You can have stippling (sand paper appearence) vs. not
-You can have a clear or not clear demarcation line
-You can have a pronounced gingival groove or a minor one
-You can also differ in the gingival width which is the length from the MGJ to the gingival margin
Oral Epithelium
-Stratified, squamous cell
-Keratinized
-Extends from the MGJ to the gingival margin except for the palate where it becomes contiguous with palatal epithelium (palate is similar to OE)
-Can be pigmented or not
Keratinized Epithelium
1) Orthokeratinized (true) - You cannot see the nucleus or make out the organelles.

2) Parakeratinized - Can still make out the nucleus because there is incomplete disintegration of organelles

4 Layers of Keratinized epithelium
a) Basal Cell Layer (stratum basale)
b) Prickle Cell Layer (stratum spinosum)
c) Granular Layer (stratum granulosum)
d) Cornified Layer (stratum corneum) - These cells fall off once they reach this layer and this is helpful in shedding bacteria
Sulcular Epithelium and Junctional Epithelium
Sulcular -Stratified, squamous cells which are NOT keratiniazed.
-Continuous with the oral epithelium and form lateral surface of the sulcus

Junctional Epithelium - Has layers of squamous cells oriented parallel to the tooth surface. Non-keratinizing epithelium.
-Serves to attach the tooth to the gingiva and seals off opening to tooth root
-It is highly permeable because it is not keratinized and has less connection between the cells
-
Junctional Epithelial
-The cells here are largely undifferentiated so there is a high turn over ration
-There are fewer intercellular junctions (less desmosomes) and a large percentage of extracellular space so it is more permeable to cells and fluids than the SE or OE; however, it is also the weakest of the tissues and is readily ruptured
-A very unique property is that it has 2 basal laminas which allow it to connect the soft tissue GCT to hard tissue (bone)
1) IBL - Binds it to enamel
2) EBL - Binds it do the gingival CT. The true BL with stratum basale attached to it

JE Defense - The junction epithelium is where gingival crevicular fluid (GCF) is found. This fluid is derived from serum that is filtered from the BV around the tooth through the CT
-Due to this, the GCF usually has immunoproteins, neutrophils, and monocytes. This makes the GCF the initial line of defense against plaque (immune cells have receptors specific to oral plaque)
-Cells of the JE release chemokine IL-8 which attracts immune cells. Also have LFA-1 which help immune cells migrate through the JE
Gingival Connective Tissue (1)
-made of gingival fibers, intercellular matrix, cells, blood vessels, and nerves

1) Gingival Fibers - Composed mostly of Collagen I and minor contribution of elastic and oxytalan fibers in the perivascular region
-Gingiva binds to the tooth through JE attachment and gingival fiber bundle attachment
-2 main types of attachments to know
a) Dentogingival - Connection of the tooth to the gingiva
b) Dentoperiosteal - Connection of the tooth to the bone

4 main functions of Gingival Fiber Bundles
1) Attach gingiva to teeth and bone
2) Secure teeth within the arches
3) Make gingiva rigid to keep its contour
4) Resist forces of mastication without being deflected

Ground Substance - Space inbetween cells, fibers, BV, and nerves. It is made of water, glycoproteins, and proteoglycans which gives gingiva the little flexibility it has
Gingival Connective Tissue (2)
Gingival CT Cells:
1) Fibroblast - make and degrade collagen. A normal degradation involves collagen phagocytosis into a phagolysosome and peptide recycling. Abnormal degradation is MMP release into the ECM which leads to inflammation
-Other cells: Macrophages,Mast Cells,MSC,Leukocytes,Bone and Cementum Cells

Gingival CT Vessels and Nerves: There is no vascularization at the epithelium (OE, SE) but the CT is highly vascularized. The blood supply ANAS through the alveolar bone, marrow spaces, and the PDL

GIngival CT Lymphatics: Drain to submaxillary lymph nodes

Gingival CT Nerves: The CN V provide sensory and proprioceptive functions. ANS endings are associated with gingiva vascular
Attachment of the Epithelium to the Tooth
- During bell stage development, the enamel organ will form the reduced enamel epithelium
-The REE will fuse with the oral epithelium and undergo apoptosis where the tooth is erupting. This is due to a lack of blood supply
-The REE/OE fusion around the tooth will become the junctional epithelium and attach to the tooth through hemidesmosomes. The OE further from the tooth remains as the OE
Basic Gingivitis and Periodontal Probe
-During inflammation PMN leukocytes (neutrophils) infiltrate the JE leading to the formation of rete pegs in the GCT
-A periodontal probe can measure the depth of the gingival sulcus to look at inflammation
-Should be 1-3mm for normal (2/3 of JE)
-During gingivitis is goes near the apical extend of JE
-During periodontitis it goes beyond JE to CT
Gingival Surgery
-lose of gingiva can make the teeth susceptible to inflammation, hinders good oral hygiene, is asethetically unpleasing, and can lead to further tooth recession

1) Gummy Smile - During eruption the JE does not descent apically. Can remove JE over tooth and the OE will dedifferentiate into JE and attach to tooth

2) Free Gingival Grafts - Transplant palatal tissue to tooth surface, heal in 6-8 weeks
Cementum Overview
-While epithelium covers the enamel, cementum covers the root and anchors the teeth in place
-Cementogenesis is directed by the Hertwigs' Epithelial Root Sheath
-Cementum is mineralized, anchors teeth to alveolar bone by PDL, and it is avascular so unlike bone it cannot regenerate as well
-Grows slowly and is 50% HAP and 50% proteins (same as bone). 90% of organic matrix is Col 1
Cementum Classifications
1) Location - Coronal (on crown) and Radicular (root surface, majority)

2) Cellularity - Acellular or cellular (has cementoblast)

3) Fibers - Afibrillar (has Col Fibrils, no Col FIbers) and fibrillar (has Col fibers)

4) Fiber Types - Extrinsics (made by fibroblast), intrinsic (made by cementoblast), mixed (made by a combination of fibroblast and cementoblast)
Where certain cementum is found
Single-rooted tooth - Has acellular, extrinsic fiber cementum

Multi-rooted tooth - Apical 1/3 cover by cellular, mixed fiber and coronal 2/3 by acellular, extrinsic fiber
Acellular Cementum Formation
-Majority of the structure found in the PDL
-As the HERS undergo apoptosis there is a signal to induce follicle cells to infiltrate and undergo cementogenesis. These cells will lay down the matrix and retract away.
-Initially the cementoblast will elongate into unmineralized mantle dentin and secrete collagen fibrils (longitudinal). Eventually they will only secrete NCP to fill in the spaces
-As the cementoblast secrete primarily NCP fibroblast will secrete collagen bundles called Sharpy Fibers (at right angle to tooth) which become trapped in the matrix (major component of PDL which holds tooth in place)
Cellular Intrinsic Fiber Cementum
-Forms later on near the apical root, quicker formation
-Starts off similar to acellular with cementoblast extending collagen fibrils into the unmineralization mantle dentin
-Then, instead of retreating, the cementoblast will secrete NCPs and collagens and become trapped in cementoid and become cementocytes
-Mixed cementum can occur if during PDL organization the cellular cementum continues to be deposited around the ligament fiber bundles. They both become trapped in the partially mineralized cementum

Cellular and Acellular differ because acellular has no cells. Additionally, cellular is secondary cementum which is involved in tooth attachment in a minor way (not in incisor or canine). It is confined to the apical and interradicular regions of the tooth
Acellular Afibrillar Cementum
-It has no cells or fibers, lacks collagen, and plays no known role in tooth attachment
-May be a anomallly because it is usually found over enamel or near CEJ
Location of Different Cementums
1) Acellular, extrinsics - Majority of the tooth, the CEJ to at least apical 1/3. In incisors and canine it covers the whole root - Used for tooth anchorage

2) Cellular, intrinsic - Found in the middle to apical 1/3 and furcas and is used for adaptation and repair

3) Mixed - Found in the apical portions and furcas, used for adaptation

4) Acellular, afibrullar - some patches over enamel and dentin, nothing known about it
Periodontal LIgament
-The main attachment apparatus to anchor the tooth to the jaw
-It is a cellular and fibrous tissue that joins the cementum to the alveolar bone. It is NOT mineralized, therefore it can move over time
-It has a large vascular and neural component (hot you seen hot/cold food) and has a high cell turnover ratio
-The PDL is composed of fibroblast, vessels, nerves, intercellular matrix, and PDL fibers
-Highly vascularized with a small potential to regenerate itself
Periodontal Ligament FIbers
-Composed primarily of Col I, but also Col III and Col 12
-The collagen fibrils are arranged in discrete collagen fiber bundles that go from the cementum to the alveolar bone
-The part stuck into mineralized tissue is referred to as Sharpy's fibers (totally mineralized in acellular cementum, and partially mineralized in cellular cementum)
-The PDL also has a immature elastic fiber known as oxytalan around the cervical portion that gives the PDL a little bit of flexibility
-Depending on their arrangement the fiber groups have named
1) Alveolar Crest - Near the JE
2) Horizontal - Apical 1/3
3) Oblique - Apical 2/3
4) Periapical - Close to the apical foramen
5) Interraddicular - Between roots on multirooted teeth

-Ground substance is between the cells, fibers, and neurovascular parts. Made of water, glycoproteins, and proteoglycans
PDL Cells
1) Fibroblast - make/degrade collagen rapidly so they can turnover the entire ECM if needed. Main cells of PDL. Large cells containing organelles associate with protein synthesis/secretion. Are oriented along the collagen fiber bundles

2) Epithelial Cells - These are the epithelial cell rests of Malazzes which come from the Hertwig Epithelial Root Sheath

3) Bone and Cementum Cells

4) Inflammatory Cells

5) MSCs - Can differentiate to osteoblast, cementoblast, or fibroblast
PDL Development
-From the dental follicle comes the cementoblast and fibroblast
-The cementum and PDL is laid down at the same time
Alveolar Bone
-The alveolar process is the portion of the jawbone that has the teeth and alveoli (tooth sockets)
-It rests on basal bone
-To develop properly it needs the tooth eruption, and without teeth it will recede
-The alveolar process can be split into 2 components

1) Alveolar Bone - Portion of the alveolar process directly around the alveoli. Made of corticol bone with lots of performations to transmit BV between the marrow and PDL
2) The most occlusal part of the alveolar bone is the alveolar crest. It is a small part that runs parallel to the CEJ
Alveolar Cont...
-Right below the tooth root you can draw a line
-Above the line is the alveolar process
-Below the line is basal bone, which the tooth rests on, and makes up the mandible and maxilla
-In edentulism, everything above the line, the entire alveolar process, disappears
Alveolar Final
-The shape of the alveolar bone follows the tooth shape and models itself after the CEJ
-Specifically, the alveolar crest modifies its shape to mirrow the CEJ, even in crooked teeth it will become crooked
Liver Function
-Largest internal organ and mass of glandular tissue
-Make toxins harmless
-Endocrine and exocrine function - exocrine is production of bile (goes out bile duct) and endocrine is production of material for the liver
Liver Structure (1)
Portal Triad - portal vein, hepatic artery, and bile ducts. These structures have CT branches that help define liver lobule
1) Blood comes in the portal vein from GI with toxins
1b) Blood comes in hepatic artery to feed blood cells
2) Blood percholates from portal vein through hepatic sinusoids (lines by endothelial cells). At sinuoids it is filtered by Kupper Cells and Hepatocytes
3) Clean blood reaches central vein and goes back to heart from hepatic vein
Liver Structure (2)
1) Classic Liver Lobule - Hexagon lobule with central vein. Has portal triads at corners of hexagon

2) Portal Lobule - A triangle around a bile duct. The triangle corners are at central veins

3) Hepatic Acinus - Diamond shape with two portal triads and 2 central veins. Arranged around branches of the portal triad components
-Further divided into 3 concentric eliptical zones.
1) First to receive O2, nutrients, toxins from sinusoids. First to regenerate, last to die
3) First to show ischemic necrosis and fat
2) Between 1 and 3
Liver and Hemapoiesis
-Principle site of hemapoiesis in gestation (can take over if marrow deficient)
-Later on erythrocytes filter through hepatic sinuisoids
Hepatocyte
-Hepatocytes are large with a very active euchromatic nucleus
-Has smooth ER for toxin inhibition, a big rER, and lots of lysosomes and microbodies
-Hepatocytes are connected by tight junctions and the space between them forms bile canaliculus
-Bile travels through the canaliculus to a bile ductules and then bile duct which empties into the hepatic ducts and goes to the gall bladder
Gall Bladder Function
-Receives dilute bile from the liver and makes it concentrated by using its columnar absorptive epithelial cells
-Bile has bile salts, phospholipids, bilirubin, and cholesterol and dissolves fats
Gall Bladder Structure
-pear-shaped and attach to liver
-Has only epithelial cells, a mucosa (lamina and mucus glands), a muscularis and adventitia (has CT, nerves, and BV)
-Has outpouches called Rokitansky-Aschoff (R-A) sinus associated with gallstones in later life
Gallbladder Structure 2
-Has columnar epithelial cells and a distended lamina propria
-Has lymphocytes in the lamina propria
-No submucosa but has mucus-secreting glands in the mucosa
Pancreas Function
-Release powerful digestive enzymes to break down carbs, proteins, and fats
-Release enzyme to neutralize stomach chyme
-Has alpha cells that made glucagon and beta cells that make insulin
-Has exocrine component
-Endocrine component is the Islet of Langerhan with A,B, and D cells (somatostatin secreting)
Pancreas Structure
-Lies witin C-shaped duodenum
Exocrine Component - Has serous cells in acini to secrete proteins
-Acini lead to a intercalated duct, which leads to a interlobular duct and then a pancreatic duct
-Has a perenchymal structure with small villi and Brunner's Gland (similar to duodenum)
-Has lots of ducts lined by simple columnar epithelium with goblet cells coming out. At surface has pseudostratified/stratified columnar epithelium
Pancreas Structure 2
-The pancreas is is surrounded by a thin capsule and divided into lobules by a CT septa
-The majority of each lobule are serous secreting acinar cells that empty contents into intercalated ducts. They release inactive zymogens so they can't work on the pancreatic cells
-Within the lobule in a small percentage are acini islets that produce peptides and hormones (A-cell on outside, B-cell on inside)
Pancreatic Ducts
1) Duct starts with centroacinar cells at acinus
2) Enters intercalated ducts which are squamous
3) Intercalated drain to the intralobulae (not striated) which are round, simple cuboidal
4) Intralobular unit to form the interlobular, have lots of CT around a simple cuboidal to columnar epithelium
5) These drain to the pancreatic duct