OSS Quiz 1
Steps of Long bone formation in Endochondral bone formation
*** Comes from mesenchymal Progenitor (cartilage to bone) Outside to inside: 1. Proliferating chondrocytes 2. prehypertrophic chondrocytes (at which point switch to synthesize collagen X) 3. Hypertrophic (recruit cartilaginous skeletal elements and drives longitudinal bone growth. Recruits mineralization of surrounding matrix and production of VEGF. Under go apoptosis whcih leaves behind matrix for osteoblasts to invade) and lay down primary spongiosa) 4. Terminal hypertrophic
Stages of tooth development
*requires interaction between epithelium and mesenchyme 1. Thickening 2. Bud 3. Cap 4. Bell 5. Erupted Tooth
Runx2
- Affect on osteoblast to osteocyte lineage
FGF signaling in bone
- Chondrocyte proliferation and differentiation
Cartilage / Chondrocyte features
- Has larger vacuole - Lacunae = The pocket that the chondrocyte sits in
Proliferative zone cells
- High o2 content and glycogen content - increased mitochondrial ATP production - separated via aggrecan and type II collagen
Functions of Epithelia
- Protection - Absorption -Secretion -Sensory
Cellular components of the skeleton - Defect in Runx2 or SOX9
- Runx2 = formation of osteoblast precursor - Sox9 = chondrocyte formation
Treacher Collins Syndrome
- abnormal arch 1 produces facial anomalies -
Synchondrosis: Located where?
-- Union between two bones (due to formation of hyaline cartilage or fibro-cartilage) -- 3 in midline of cranial base - --- Spheno-ethmoidal ---intersphenoid --- spheno-occipital (can grow bidirectionally as opposed to others)
What pharyngeal arch gives rise to teeth?
1
What is derived from Ectoderm?
1. Brain, Skin, Teeth, hair
1. Epithelial Neoplasm 2. Mesenchymal neoplasm
1. Carcinoma 2 Sarcoma
1. Pinocytosis 2. Receptor-mediated endocytosis 3. Phagocytosis
1. Cell "sipping" extracellular fluid into vesicles 2. Solid particles 3. Clathrin coated pits
1, Pluripotent 2. Totipotent 3. Multi
1. Cells that are capable of developing into any embrylogical origin 2. Can become anything in embryo and extra embryological cells 3. Can develop within specific lineages
1. Jansen Metaphyseal chondrodyslplasia 2, Bloomstrand lethal osteochondrodysplasia
1. Constitutively active PPR or High PTHrP = PTHrP inhibits hypertrophy so osteochondrocytes never mature and bones are short 2. Inactive PPR mutation = No PTHrP to stop hypertrophy so have decreased proliferation = increased hypertrophy and differentiation (causing decreased bone growth)
How to treat aggressive periodontal inflammation
1. Control inflammation 2. Bone 3. Microbial community colonization
Periodontal ligamnet is derived from the?
1. Dental Sac
Morphogen Transport models 1. Restricted Diffusion 2. Planar Transcytosis model 3. Lipoprotein Transfer model 4. Cytoneme model
1. Dependent on number binding induces certain gene expression 2. Transport through the cells 3. 4. Pseudopods help transfer morphogen
1. Surface Ectoderm 2. Neural Crest 3. Neural Tube
1. Epidermis, hair, nails, sebaceous glands, oral epithelium, teeth (enamel) 2. PNS, dentin, facial cartilage, 3. CNS, brain, spinal cord
Mechanisms of Bone formation
1. Intramembranous (frontal, parietal, temporal bones) 2. Endochondral Bone Formation (appendicular, vertebrae, base of the skull
hereditary ectodermal dysplasia
1. Most commonly x-linked - Thin hair - discolored skin - Peg incisors - Hypohidrotic = less sweat - Hypotrichosis = less hair - Caries b/c no PDL, missing teeth Have over 150 types b/c can have anywhere within the pathway (EDA, EDAR, EDA-RAAD)
Order of growth:
1. Neural 2. Lymphoid 3. General body 4. Genitals
Functions of ECM
1. Supportive, mechanical 2. Substrate for adhesion/ migration 3. permissive and instructive for cell differentiation 4. Factor for cell survival
Smooth ER functions
1. Synthesis of lipids, phospholipids + steroids 2. Detoxifies via Cytochrome P450 3. Sequestration of Ca2+
Tongue Development 1. Begins at and formed from
1. Week 4 - Anterior 2/3 = lingual swellings - Posterior 2/3 = copula and hypobranchial eminence
Bell Stage
11 weeks Tooth shaped bud occurs - enamel organ is defined - composed of stratum intermedium and reticulum
Week 4 -10
4 = mand/ max 5 = nasal pits 6 = front nasal pits fuse/ secondary and primary palate form 7. Palate shelves elevate 10. Fusion of secondary and primary palates and nasal septum (defect results in cleft palate)
Initiation stage
6 weeks - ectomesenchymal cells induce overlying ectoderm to proliferate into dental laminal
Bone is Composed of
60% inorganc material 30% organic material 10% water
Bud Stage
8 weeks Form: 1. Dental Lamina 2. Condensing Mesenchyme - ectoderm and mesenchyme proliferate around bud - Localized thickening at site of each tooth (can see condensing mesenchyme)
Cap Stage
9 weeks: - Dental papilla forms from condensed mesenchyme (indentation starts to make pulp) Form: - Outer enamel epithelium - Inner enamel epithelium - Lose Stellate Reticulum Later dental sac/ follicle forms
Why Mouse Models
>99% are the same
Accessory Root canals can be formed by
A break in the root sheath before formation of dentin
PPR
Active PRP (in prehypertrophic) = stops hypertrophy increase proliferation Hypertrophic chondrocytes = secrete IHH which cuases increase in PTHrP secretion PTH and PTHrP receptor = expressed in low level in Proliferative Chondrocytes = Expressed in high levels in Prehypertrophic and hypertrophic chondrocytes
Adnexal Appendages derived from?
All have placode and bud stage Ectoderm (i.e. epithelial bud) - Therefore hair follicle and mammary glands / teeth/ salivary glands would be affected if epithelial bud stage affected
After EMT neural crest cells can migrate how? Somites
Along Dermomyotome (limb/;body, skeletal muscles, dermis or Sclerotome (vertebrae / ribs) SOmite = lateral to neural crest mesoderm
Apoptosis vs. Necrosis
Apoptosis doesn't cause inflammation
Arch I forms frontonasal prominence and meckel's cartilage
Arch
Where do neural crest cells form?
At the boundary of the neural and non-neural ectoderm
Tooth type determined by?
BMP (incisor) and FGF (molar) signaling
Mucinocele
Blue nodule, well demarkated, excisional biopsy (
Mandibular and Maxillary formed from
Both undergo intramembranous ossification
Sutures are assisted by
Brain comes forward and induces the cranial vault (top) to grow because don't have synchondrosis which have cartilage to assist in the growth of the bone.
Accessory root canals can be formed via?
Break in root sheath before formation of dentin
5 Signs of acute inflammation
Calor, dalor, redness, tumor, loss of function
IHH deletion
Causes no Ihh secretion leading to No PTHrP production causing early differentiation. Does not grow in the length, the bone.
Cillia vs. Microvilli
Cillia = motile Microvilli = increased surface area for absorption
Rough ER composed of
Cisternae (flattened membrane disck,) and ribosomes
Example of a collagen that is also a proteoglycan
Collagen 18
Articular Cartilage is composed of
Collagen that has: Proteoglycans = bind water Hyaluronic acid - binds water (made of di-saccharide repeat) Collagen fibrils - Aggregan - bottle-brush molecule (core protein that binds water molecules)
Cre-Lox mouse
Cre targets a specific sequence of DNA =
OPG
Decoy receptor for RANKL to block osteoclast activity (produced by osteoblasts)
ACH achondroplasia
Defect in FGFR3 normally inhibits proliferation (mutation = an activating mutation) and prevents proliferation causing => early differenitation and short extremities
Cleidocranial Dysplasia
Defect in Runx2 - Osteoblast lineage mesenchymal stem cells to osteocytes --- often born without clavicles or open fontanels
Dental Papilla vs Dental Follicle Dental lamina
Dental papilla = ectomesenchyme Dental sac= forms cementoblasts (cementum) Lamina = epithelial
Area at which calcification of a tooth begins
Dentinenamel junction
Derivation of epidermal Tissue from ectoderm
Derivation of epidermal tissue = BMP produced from ectoderm induced epidermal tissue
Morphogens
Diffusible biochemical molecule that forms a gradient (ex. placode induction)
Lysosome
Digests organelles, with several 40-50 hydrolytic enzymes - Low pH environment (optimal activity for enzymes)
Early vs. Late migrating cells
Early = form dorsal root ganglion and heart/ adrenal gland Late = melanocytes after dermis invasion
Bone Arises from?
Ectoderm and mesoderm
Multiple root formation in a tooth follows unequal proliferation of the?
Epithelial diaphgragm (turning of the apical root sheath)
Multiple root formation in a tooth follows proliferation of
Epithelial diaphragm
Tissue Recombination experiments
Epithelial induces it but Mesenchymal determines (the fate) .Kidney = invovled in EMT ; liver is not involved in EMT
What closes the growth plate
Estrogen
Trophectoderm cells
Extraembryonic cells (on outside) with inner cell mass on inside
Neural Crest cells are pluripotent
FALSE (I THINK) = Pluripotent stem cells: Can make all three layers
Neural Crest found in other non vertebrates
False
Periosteum - Layers
Fibrous layer covers bone (plays role in bone strength and tissue regeneration 1. Endomesial layer (mesenchyme) -- involved in regeneration 2. Outer layer = fibroblastic (plays structural layer)
Apposition
Formation of crown - First = odontoblasts (secrete dentin matrix) - 2nd = ameloblasts secrete enamel matrix
Which branchial arch gives rise to thyroid cartilage?
Fourth
What causes the mesoderm to form?
From Nodal and Wnt Signaling from epiblast cells
What is derived from endoderm?
GI tract, liver, pancreas, gallbladder, resp tract lining
PAS stain stains
Glycoproteins in wall ("periodic acid shift stain")
Synchondroses bone growth
Growth = similar to long bone growth (but Bipolar) and used via endochondrial
HED symptoms
Hereditary Ectodysplasin
Derivatives of the branchial arches
I = maxillary artery, trigeminal V, muscles mastication, II = hyoid, stapedial , facial VII, muscles of facial expression , stapes III = internal carotid, glossopharyngeal IX ,
What collagens are invovled in interarticular cartilage
II, XI, and XIV
Stem cells for endochondrium are located where?
In the resting zone
Role of 4-hydroxyproline
Increases melting temperature of collagen
Sclerostin
Inhibits Wnt --> decreased bone formation
Endosteum
Inner layer (lines bone cavity) Skeletal homeostasis role i.e. consists of osteoprogenitor cells -
Overall Signaling Pathway
Intermediate BMP + FGF + Wnt => Pax3 and Zic 3 which then induce Snail and FOXD3 forming the neural crest
Neural plate border genes (i.e. cells that will form neural crest cells) formed via what signaling?
Intermediate levels of BMP and Wnt and Fgf induce Neural Place border genes i.e. Pax3 and Zic3) which induce Via induction of Snail Gene ( ( which then causes development of the Epithelial-mesenchymal transition High BMP would be ectoderm Low BMP would be neural tube
Cytoskeleton
Intracellular scaffolding -
Maxilla grows via
Intramembranous
Gingivitis Periodotitis
Irreversible = periodontitis (progresses past the CEJ) Reversible = gingivitis
Collagen V role
Lots of collagen V = small diameter fiber
4th week of embryonic development the first branchial arch divides to form
Maxillary and mandibular processes - Meckels cartilage dissolves as the mandible forms (5th week nasal pits form)
Failure of fusion of which embryonic processes cause cleft lip and palate
Medial nasal and maxillary and maxillary
What determines type of tooth
Mesenchyme
Week 6 Brachial arch I End of week 6
Mesial nasal porcesses merge with each other AND maxillary process Mandibular processes fuse End of week 6 -- Primary palate forms becomes part of premaxillary
Derivation of Neural Tissue from ectoderm
Mesoderm produces noggin which inhibits BMP (produced from ectoderm) This causes formation of neural tissue **Works with Chordin as well ****This induces the Neural Plate to form Neural tube/ (CNS) with the neural crest cells coming off of it (PNS)
Osteoclasts come from -important differentiator for macrophages?
Monocytes (same as macrophages) Come from hematopoietic stem cells -Know cathespin K
What is derived from Mesoderm?
Muscle, bone = forms cranial vault bone -- Formed from cells from primitive streak -- Formed from Wnt and Nodal signaling from epiblasts in the ectoderm layer
4-5 week development
Nasal/ olfactory placodes from nasal pit - FORM lateral and medial nasal placodes
Skull derived from
Neural Crest (from ectoderm) = Frontal, maxilla, mandible Mesoderm = Fronal, parietal, occipital
Dentin Formed from
Neural Crest (via odontoblasts)
• When the definitive mandible forms and meckel's cartilage dissolves, what structure remains as a remnant?
No remnant remians in the adult
Wnt and BMP signaling in tooth
Oral ectoderm induces odontogenic mesenchyme and vice versa
Mucopolysaccharidoisis
Oral manifestations - Micrognathia (MPS I) - Macroglossia - Gingival hyperplasia
Osteocytes formed form
Osteoblasts
Week 7 Development
Palatal shelved
Peripheral Nerve Bundle
Perineurium/ axon/ myelin
Osteoclasts form what on bone
Pits (and can their see multinucleated cells
Primary versus Secondary Ossification
Primary = below growth plate Secondary = above growth plate
WEEK 6 continued... Cleft lip palate can occur due to failure of
Primary palate (from medial nasal processes after merge with maxillary process on each side) and secondary palatal shelves (form maxillary process)
Initial epithelial attachment joining gingiva to tooth
Reduced enamel epithelium
The epithelial attachment joining the gingiva to the tooth arises directly from?
Reduced enamel epithelium
Ihh regulation invovled in
Regulates the onset of hypertrophic differentiation - expressed in more mature cells of the growth plate (prehypertrophic and hypertrophic) induce PTHrP expression in Resting round chondrocytes which then acts back on prehypertrophic chondrocytes on their PPR receptor to stop hypertrophy (keeping more cells in proliferative phase) - Increases condrocyte proliferation (but PTHrP negatively feeds back inhibiting IHH)
Bone modeling vs remodeling
Remodeling = formation and reabsorption on both sides (occurs on endosteal surface) Modeling = reabsorption on one side, formation on the other (early on in life
The growth plate is
Responsible for bone length growth -- and it involves the formation and differentiation of chondrocytes - located between epiphyseal and metaphyseal one
Which branchial pouch gives rise to the palatine tonsils
Second
Increase in BMP causes medial expression of ____along neural plate
Snail gene (Snail gene = neural crest when it is a part of the ectoderm) **Snail = induced by intermediate levels of BMP High BMP = ectoderm Low BMP = neural Noggin + Chordin (from mesoderm) = inhibit BMP
Bones that form via Intramembranous
Squamous part of temporal bone, ethmoid, sphenoid parietal, Maxilla and mandible
Root Formation =
Starts at 14 weeks in utero - HERS (Hertwig's epithelial root sheath) at epithelial diaphragm angles inward - HERS disintegrates leaving epithelial rests of malassez -- Follicle cells migrate and differentiate into cementoblasts, osteoblasts and fibroblasts
Prehypertrophic zone
Synthesize (collagen Type X) - Secrete Ca, hydroxyapatit, phosphatases, and metalloproteinases (MMPs)
Gastrulation
The process by which a blastula develops into a gastrula with the formation of three embryonic layers - specifically with the mesoderm inbetween the ecto- and endoderm
Bell Formation
Tooth shaped bud occurs "morphodifferentiation" Histodifferentiation occurs"
Vertebrates are ____blastic
Triploblastic
Common structural property that defines the proteins in the collagen super family?
Tripple helix
Pharyngeal arches developed from?
Ventrally migrating (cranial neural crest cells)
Vitamin required for fibril formation
Vitamin C
Tooth Stage Initiation
Week 6 Dental Lamina is induced and formed from underlying mesenchymea
nucleolus
Where ribosomes are synthesized
Neural Crest fox domestication example
Whiter foxes = more domesticated (b/c lack neural crest cells that don't populate the adrenals i.e. don't migrate as far along with adrenal glands) - have white tips, etc.
Neural Crest in addition to Intermediate level of BMP requires what signal to form
Wnt and FGF Signaling (inducing Pax3 and Zic1)
Which nerve is associated with 2nd pharyngeal arch
facial
What are major functions of proteoglycans
hydrated sturdy proteoglycans
CathespinK
produced by osteoclasts after NFATc1 pathway activiated through RANKL == leads to functional osteoclasts
Fibroblasts
synthesize extracellular fibers - Have spindle shaped extracellular matrix / collagen
Resting zone of growth plate houses
unique stem cells (can differentiate into bone cells for growth, repair and maintenance
Zones of periosteum
zone 3 = outer fibrous layer Zone 2 = Cambium layer Zone 1 = Osteoblasts