Epithelium

• epithelial tissue cover nearly all surfaces of the body, both internal and external
• genearlly form broad sheets that do not contain blood or lympathic vessels
• basal surfaces are attached to underlying connective tissue along basal lamina 
• derived from all three germlayers: ectoderm, mesoderm, and endoderm 

Epithelial Function

• function in protection, absorbtion, filtrations, secretion, excretion and movement 

Epithelial Cell Attachment

• attachment to surrounding tissue and adjacent cells is carried out by cell adhesion molecules and larger cell juntion complexes
• Ca2+ dependent and independent Cell adhesion
• variety of cell junction complexes 

Ca²⁺ Dependent Cell Adhesion Molecule 

• over 40 different types
• two main types are E- Cadherin and selectins

E-Cadherin

• Dependent on levels of Ca²⁺
• two cadherins form a cis-homophillic dimer in plasma membrane of one cell
• a specific amino acid sequence allows binding toa  cadherin dimer on another cell in a trans-homophillic interaction
• the cytoplasmic domains are attached to actin cytoskeleton by a caterin complex 

Catenin Complex

• helps bind cadherin to actin cytoskeleton 
• complex contains α, β, and γ plakoglobin as well as actin binding proteins 
• the β protein binds to cadherin and the α and γ plakoglobin attach to the actin
• β can also act as a transcriptional factor 

Selectin**

• contain specific carbohydrate recognition domains that bind to oligosacch on glycolipids, proteins
• on surface of endothelial cells and mediate interations with white blood cells and plateletes in blood stream

Ca²⁺ Independent Cell Adhesion 

• integrins are one type 
• cell adhesion molecules in immunoglobulin subfamily 
• these are Intercellular cell adhesion molecule 1 and 2
• (ICAM 1 and 2)

ICAM and VCAM***

• play important role in TCell interactions and binding of leukocytes to activated or resting endothelial cells

Endothelial Cell Junction Complexes

• Tight Junctions (Zonula Occludens)
• Belt Desmosomes (Zonula Adherens)
• Spot Desmosomes (Macula Adherins)
• Hemidesmosomes
• Gap or Connecting Junctions

Tight Junction

• occluding junctions or zonula occludens or terminal bar
• formas a gasket that joins apical edges of adjacent epithelial cells together
• seperates apical and basolateral domains
• forms barrier that prevens free difusion of stuff
• occludin/clauidins, junction adhesion mol., zonula occludin proteins all involved in junction

Occludin/Claudins

• part of a Tight Junction
• forms linear fibrils btween adjacent epithelial cells

Junction Adhesion Molecules

(JAM)

• part of a Tight Junction (Zonula Occludens)
• forms trans-homodimers at tight junctions
• also involves Nectin

Zonula Occludin (ZO)

• part of a tight junction
• ZO-1, ZO-2, ZO-3 and afudin
• these are cytoplasmic proteins that connect nectin, JAMs, occludins, and claudins to the actin cytoskeleton

Belt Desmosomes

Zonula Adherin

• similar to tight junctions, also forms circumferential gaskets
• also attaches to actin cytoskeleton
• uses a afadin-nectin complex
• has caterin complex
• has dense plaque on internal surface of pm that serves for anchoring of afadin and cadherin
• desmocollios/desmogleins form trans homodimers with adjacent cells (cadherins

Spot Desmosomes

• Macula Adherins
• forms isolated patches of attachment
• share configuration of cadhers and plaques as belt
• however, attaches to keratin intermediate filament cytoskeleton through desmoplakin

Hemidesmosomes

• similar in appereance to half spot desmosome
• also attach to keratin intermediate filament cytoskel
• do not contain same biological components
• have internal plate and cell membrane plaque as well as BPAG, Pectin, Integrin α₆β₄ and lamina 5

BPAG-1 and Pectin

• components of hemidesmosome
• they both attach the plate to the intermediate filament cytoskeleton

Lamina 5

• part of hemidesmosomes
• anchors cell membrane plaque to basal lamina

BPAG-2

• part of a hemidesmosome
• attaches BPAG-1 to the basal lamina

Integrin α₆β₄

• part of a hemidesmosome
• in the cell membrane 
• links pectin to the basal lamina

Gap Junctions

• aka connencting junctions
• pores btw adjacent cells fromed by end to end connection of connexons
• all molecules of up to 12 nm diameter pass btw(Ca2+ and cAMP
• connexons are formed from six connexin monomers

Motile Cilia

• cell projection aranged around a 9+2 arangement of microtubles (axoneme)
• movement of these provide mechanical force to propel overlying fluid layers

Primary Cillium

• single non-motile cilium that has same 9+2 arangement
• function primarily in cell signalling in organogenesis

Basal Bodies

• cilia develop from thes in the apical domain
• derived from centrioles (centr. have 9 triplets)
• anchored by rootlets

Microvilli

• non-motile cell projections aranged around a core of cross-linked G-Actin microfilaments
• provide increased Surface area for absorbtion 

Stereocillia 

• bear little resemblance to cilia
• non-motile, branching cell projections (G-Actin)
• provide increased surface area for absorption 

Squamos Cells

• flattened epithelial cells
• cover large surface area and thinness allows for rapid trans-cellular material exchange
• nucleus and cell look like fried egg

Cuboidal Cells

• Roughly cube-shaped
• often highly polarized and participate in active absorption and secretion 

Columnar

• taller then they are wide
• most commonly associated with absorption
• nuclei are found near their base

Simple Cell Stratification

• single layer of cells a top the basil lamina

Stratified Cell Stratification 

• multiple cell layers where some cells do not contact basal lamina 

Pseudostratified Cell Stratification

• All cells are in contact with basal lamina
• howerver, not all cells are tall enough to reach the lumen

Keratinized Stratified Squamos

• outermost cell layers lack nuclei
• modified to deal with mechanical stress
• found in skin cells 

Transitional Epithelium

• Urothelium
• all cells attached to basal lamina but not all reach the lumen (like pseudostratified)
• aggregated protein plaques on apical surface linning the lumen
• assist in mainting osmotic gradient found btw urine and internal urothelial cells in lumen of bladder 

Serous Secretions

• Proteins in watery aqueous solutions secretied from exocrine glands (merocrine secretion)

Glycoprotein Secretion

• have protective and signaling function
• mucous secretion is example (merocrine secretion)

Lipid Secretion

• source of norishment in breast milk, barrier to water loss in skin
• occur by either apocrine or holocrine secretion

Peptide Secretion

• Amino Acid Chains that function in cell signaling by binding to cell surface receptors

Exocrine Cell Development

• stalk of epithelial cells form a duct that is continuous with the external surface of the epithelium
• secretions release out of this duct

Endocrine Cell Development

• stalk that connects secretory portion to epithelial sheet goes through apoptosis, leving the portion in the connective tissue

Endrocrine Gland Structure

• can be simple or compound (branched)

Tubular Endocrine Gland 

Morphology

• secretory portion forms an elongated tube
• can be branched or coiled tubular

Alveolar Endocrine Gland Morphology

• also known as acinar 
• secretory portion forms rounded clump of cells around a central lumen
• tubuloacinar morphology can exist

Large Compound Endocrine Gland 

Morphology (lungs)

• Divided into lobes by interlobar septa of conective tissue
• lobes are further divided into lobules by interlobular septa
• drain into interlobar ducts that drain in to interlobular ducts

Mesenchyme

• variable cell shape
• embryonic cells perpituats connective tissue
• euchromatic nuclei
• develop from mesoderm
• mostly viscous ground substance w/ few colagen fibers

Mucoid (Mucous) 

Connective Tissue

• embryonic 
• also known as wharton jelly in umbilical chord
• mainly in umbilical chord 
• elongate or ____ fibroblasts
• simple ground-very little colagen 
• jelly like

Loose (Alveolar) Connective Tissue 

• elongate fibroblasts
• fine collagen fibers
• frequently conducts and surronds blood and lymphatic tissues
• thick layer beneath epithelial linning of digestive system and between muscles and nerve fibers

Dense Irregular 

Connective Tissue

• elongate fibroblasts
• greater proportion of collagen fibers to ground substance
• irregular 3D "Feltwork"
• resists unpredictable load direction
• randomly interwoven
• usually asociated with Loose Connective Tissue

Dense Regular

Connective Tissue

• elongate fibroblasts
• large collagen fiber bundles to ground substance
• organized in parallel
• tendons and ligaments
• meant to resist prolonged stress in same direction

White adipose Tissue

• unilocular adipose tissue
• single locus of triglyceride storage per cell
• displaced nucleus(singet ring) against plasma membrane
• relative long term energy storage specialization

Brown Adipose Tissue

(multicellular adipose tissue)

• smaller then white adipose
• many loci of triglyceride per cell
• rounded nuclei
• found in newborns and slowly disapears in growingup
• adults around kindeys. aorta, adrenal gland, mediastinum
• brown from many mitochondria and blood vessels
• mainly heat production

Reticular Tissue

• branching network of collagen III fibers
• stellae fibroblasts
• forms stroma of lymph nodes, spleen, and liver
• formed by reticular cells (modified fibroblasts)

Fibroblasts

• spindle shaped in adult tissue
• synthesize fibers(collagen, elastin, reticulum) and ground substance
• originate from mesenchyme cells
• targets of many growth factors

Fibrocytes

• smaller, less active fibroblast
• contains darker, heterochromatin, nucleus
• less Rough Endoplasmic Reticulumn 

Ehlers-Donlos Syndrome 

• Group of diverse disorders
• results from a defect in collagen synthesis and structure
• abnormal collagen is devoid of tensile strength and skin is hyperextendible and vulnerable to trauma
• the joints are hypermobile
• also extends to blood vessels and internal organs resulting in tissue rupture and detachment

Elastin

• make up elastic fibers
• fibulin 1 and fibrillin 1 and 2
• adds bounce to skin
• older you get. less you make

Ground Substance

• highly hydrated 
• composed of GAGs, proteoglycans, glycoproteins
• transparent,, complex network
• interstitial fluid
• allows for osmotic pressure release and transport of metabolic waste

Macrophages

• irregular border
• nuerous vesicles
• eccentric nucleus
• antigen presentation, cytokine secretion
• removal of dead cells, tissue debris and turnover of protein fiber 

Mast Cells

• numerous basophillic granules
• mediate inflammatory respone
• irregular shapped Connective tissue cell
• specialize in release of many bioactive jobs
• detect invasions of microorganisms
• nucleus located centrally

Plasma Cells

• B-lymphocyte derived antibody producing cells
• clock face or cart wheel nucleus
• basophillic cytoplasm due to abundance of RER

T-Lymphocyte 

• heterochromatic nucleus 
• cell mediated immune response
• activation of antibody response
• thin rim of cytoplasm
• type of wite blood cell derived in bone marrow
• diapedesis

Integument Barrier function

• protects from mechanical trauma, abresions
• adipose tissue protects from heat loss
• melanin protects from UV light
• Toxic aqueous compounds and water loss
• protects against pathogens

Integument Function Transmitter 

• sense of touch, temperature, and pain 
• evaporitive cooling for thermoregulation(sweatglands)
• Vitamin D3 synthesis from UV absorbtion
• Olfactory and visual signals

Thick Skin

• Palm of hand and soles of Feet
• glaborous(hairless)
• lacks pigment
• eccrine sweat glands 
• 400-1400 um thick
• k1/k9

Thin SKin

• 75-150um
• can be villose (hairbearing)
• pgimented
• apocrine, eccrine and sebaceous glands
• k1/k10

Epidermal Cell Types

• keratinocytes(80%)
• melanocytes(10%)
• 1 melanocyte for every 6 keratinocytes
• dendritic (langerhans) cells 8%
• tactile epithelial(merkel) cells 12%

keratinocytes

• in epidermis
• ectodermally derived
• synthesis keratins, lamellar granules, keratohyaline granules
• abundant desmosomal connectures with neighboring keratinocytes
• provide mechanical, UV and chemical protection
• sequester melanin from melanocytes(cytocrine sec)

Keratin Dimer

• made up of one type 1(acid) and one type II(basic/neutral) keratin

Filaggrin

• cross links and stabilizes keratin

Melanocytes

• neural crest derived (ectoderm)
• located among cells of stratum basale (connected to basement membrane)
• synthesize and secrete melanin to basal and suprabasal keratinocytes

Melanogenesis

• DNA photodamage of keratinocytes may initiate production
• tyrosinase converts tyrosine to DOPA
• this converted to types of melanin
• melanin accumulates to make melanosomes

Melanin

• absorbs and scatters UV light in the Nucleus
• also functions as cheelator 
• cheelators pack heavy metals into keratinocyte for secretion

Dendritic (Langerhans) Cells

• monocyte derived macrophage 
• antigen presenting cell for T-lymphocytes
• mostly spinous layer
• connecting to keratinocyte to cytoplasmic process
• something cannot pass trhough with out elerting them
• contain langerhans vesicle and birbeck granules

Tactile Epithelial Merkel Cells

• neural crest derived
• location stratum basale
• light touch sensation
• abundant in highly sensitive skin
• contact unmylinated sensory fibers in basal lamina

Layers of Epidermis

• S. Corneum
• S. Lucidum
• S. Granulosum
• S. Spinosum
• S. Basale
• order is from most outer to most inner

Stratum Basale

• cuboidal or columnal cells at dermal epidermal point
• contains epidermal stem cells
• keratin k5 and k14 made here
• If tumor originates here it will have those keratin
• metanocytes, tactile epithelial and some dendrities

Stratum Spinosum

• early differentiating keritanocytes
• thickest layer of epidermis
• keratin activity synthesized k1/k10(thin skin) and k1/k9 (thick skin)
• central nuclei
• tonafibrils are bundeles of keratin that holds things together

Stratum Granulosum 

• three to five layers of cells nder going the terminal differenciation proccess of keratinization
• k2/k10
• basophilic heratophyaline granules filled w/ flaggrin
• lamellar granules that exocytosi to creat lipid rich barrier for protection and water loss prevention

Stratum Lucidum

• occurs only in thick skin
• nuclei and organelles have been lost
• cytoplasm exists entirely of packed keratin 

Dermoepidermal Junction

• consists of epidermal pegs from S. basale and spinosum and dermal papillae
• looks like interlocking teeth
• resistance to shear stresses

Anchoring Fibrils

• type VII collagen
• join lamina dense to papillary derma
• lamina densa (IV, V) acts as filter to resist movement of particles greater then 40KD

Papillary Dermis

• loose connective Tissue
• type I and III collagen and elastic fibers
• helps keep heat in body through blood movements
• proteoglycans, GAG's, and glycoproteins
• fibroblasts, macrophages, mast cells, dendritic cells

Subpapillary Plexus

• neurovascular plexus between papilary and reticular dermis

Reticular Dermis

• thicker layer
• dense irregular connective tissue (type I, III), elastin and claunin
• lower amount of similar ground substance as papilary dermis
• horizontal anterior plexus in deep portion

Hypodermis

• increase in adipose tissue
• organized into fatty acid membranous tissue
• fatty layer is loose CT invested w/ adipose
• conducts superficial major nerves and blood vessels
• promotes lipid uptake and insulin and drugs here

Hair

• shaft, root, and associated structures
• shaft contains cuticle, cortex, medulla (hair keratins)
• root is in dermal papilla and has inner and outer root sheaths
• subaceous gland and arrector pili

Arrector Pili

• small bundle of smooth muscle cells
• pulls hair shafts to more errect position
• in dermal papillary 

Eccrine Glands

• Simmple, coiled glands
• produce watery secretion(sodium, chloride, urea and ammonia
• most numerous on foot of soles
• secretory portion between reticular dermis and hypodermis
• regulate temperature through evaporitive cooling
• ducts stain dark and secretory part more pale
• respond to cholinergic stimulation

Apocrine Glands

• produces mostley oderless milky secretion, protein rich
• not fully functional until puberty
• respond to adrenergic signaling
• when proteins get broken down by bacteria they smell

Sebaceous Glands

• unilobular or multilobular with common duct
• holocrine secretion into secretory duct
• controlled by androgens
• not found in thick skin
• empties into upper protein of hair folicle
• secretes sebm of epidermis and hair(high lipid content

Nail

• Arise from epithelial fold
• heavily keratinized cells of nail plate grow from nail matrix at base of fold
• nail bed underneath nail
• dermis beneath nail bed attaches to underlying phalanx as skin ligament

Tactile(Meissners) Corpuscles

• unmyelinated dendrite in dermal papilae of thick skin, lips, genitalia, and nipples
• encode light discreminatory touch
• decline in # slowly after puberty 

Free Nerve Endings

• unmylinated dendrites w/o a connective tissue capsule
• pain, warmth, heat and cold
• in papillary dermis and extends lower
• mechanical, themal and chemical

Lamellated (Pacinian) Corpuscles

• deep in dermis or hypodermis
• large oval structures
• similar to tactile corpuscle
• sense pressure, vibartations and coarse touch
• found in urinary tract, bladder, rectum

Mammary Glands

• 15-20 lobes seprated by suspensory ligaments
• lobes empty into lactiferous ducts that empty into lactiferous sinus
• during pregnancy, estrogen and progesterin promote proliferation and activation of mammary glands but inhibit prolactin
• after parturition prolactin levels increase to promote lactation
• lipid in milk by apocrine and prolactin by merocrine 
• also have immunoglobulins from plasma cells

Blood 

• plasma, buffy coat, red blood cells
• connective tissue
• plasma=ECM(mostly made of water)

Plasma Content

• mostly water
• albumins
• globulins

Albumins

• smallest, most abundant plasma protein
• synthesized in liver
• maintains osmotic pressure in blood
• found in the plasma

Globulins

• immunoglobulins are antibodies secreted by plasma cells
• non-immune globulins are secreted by liver
• α and β functions in ion-transport(zinc and iron)

Fibrinogen

• in plasma 
• converts to fibrin to create blood clot during clotting
• synthesized in liver (largest plasma protein

Formed Elements of Blood

• Erythrocytes, Leukocytes and thrombocytes(platelets)

Erythrocytes (RBC)

• anucleate, biconcave, lack organelles and 7microns
• have hemoglobin that bind iron (iron allows for eosin binding)
• disc shaped to facilitate gas exchange
•  allows more Hb closer to plasma member
• actin, spectrin and glycophorin facilitate flexibility of cell

Glycophorin

• in Erythrocytes
• attach cytoskeleton protein network to cell membrane
• also play role in blood typeing
• attachment for A, B, and O antigens

Heriditary Spherocytosis

• mutations in cytoskeleton
• cause anemia, jaundice and splenomegaly
• RBCs become spherical and sent to spleen to be destroyed
• get stuck in splenic chord and bulid up of them and macrophages enlarges spleen
• causes excessive RBC production and anemia
• treatment and blood transfusion and partial splenectomy

Leukocytes

• larger then RBCS
• contain primary granules(difficult to see on light microscope)
• lysosomes to digest bacteria
• cells can leave blood stream and enter ECM
• granulocyte (-phil) and agranulocyte (-cyte)

Migration of Leukocytes

(Diapedesis)

• endothelial cells release selectins 
• leukocytes bind to selectins and slow down
• WBC integrins then bind with ICAM-1 on endothelial lining
• pases through vessel (Diapedesis)
• will then introduce inflamation

Never Let Monkeys Eat Bananas

• most abundant to least abundant WBC
• Neutrophils, eosinophi, basophi (granulocyte)
• lymphocyte and monocyte(agranulocyte)

Neutrophils

• lobulated nucleus, pale cell
• capable of one single phagocytosis
• induces infalmation
• release of chemokins and more(oxidative radicals)
• kills bacteria and them selves (kamakazi)
• first line of defense(stored and released in great amounts
• held also in venules and veins of important areas

Eosinophils

• WBC
• hamburger granule
• bilobed nucleus
• "meat patty" contains major protein that disrupts membrane of protozoa and parasites
• attack larvae
• can be cause of chronic inflamation

Basophils

• s-shaped nucleus with basophilic granules(heparin and sulfated GAGs)
• heparin is an anticoagulant(inhibits clotting
• involved in hypersensitivity and anaphalaxis

Lymphocytes

• sphericle nucleus w/ pale rim of cytoplasm
• initially immunoincompetent
• antigen exposure make them competent
• recirculate btw blood and ECM
• T-lymphocytes and Blymphocytes

T Lymphocyte

• produced in bone marrow, mature in thymus
• cell mediated immunity

B- lymphocyte

• produced and mature in bone marrow
• differentiate into antibody secreting plasma cells

Monocytes

• WBC
• kidney shaped nucleus
• give rise to connective tissue macrophages
• travel to sites of inflamation
• phagocytose bacteria and present antigens to t lymphocytes

Thrombocytes (platelets)

• membrane bound and anucleate
• smaller then RBCs
• membrane covered in glycocalyx cell coat
• open canalicular sytem for substance release from granules
• continuously moniter endothelial cells for damage
• participate in blood coagulation

Alpha Granule

• contained in platelets
• vessel repair and coagulation
• platelet aggregation
• uses plasminogen and platelet derived growth factor

Delta (Dense Core) Granules

• contained in platelets
• platelet adhesion and vasoconstriction
• ADP, ATP and seratonin, histamine

Platelet Plug

• glycocalyx on platelets bind collagen and plug damage to endothelium

Plasmin

• dissolves blood clots

Pleuripotent Stem Cells

• found in bone marrow
• give rise to myeloid and lymphoid cell lineage

Red Bone Marrow

• site of hematopoesis
• stroma and sinusoid compartments butt together at this point
• stroma contain hematopietic stem cells, Colony forming units (CFU) and maturing WBCs

Trends in hematopoiesis

• decrease in cell and nucleus size
• cytoplasmic staining properties change 

Erythropoiesis

• develop in the myeloid series
• regulate dby erythropietin (made in kidney)
• causes proliferation and differentiation
• proerythroblast(large, blue)
• basophilic erythoblast (smaller nucleus, very blue)
• polychromatophilic(even smaller, pinks and blues)
• orthochromatohpilic (real small and salmon color)

Leukopoiesis

-needs more info

• granule formation, monycte and lymphocyte
• granule: myoblast(nogranules)-promyelocyte (primary granules)- melocyte (primary graunules and first apearance of secondary granules)
• monocytes exit bone marrow and enter connect tissue
• lymphocytes immunoincompitent progenitor

Thrombopoiesis (Platelet Formation)

• controlled by thrombopoetin(made in liver)
• megakaryocyte CFU to megakaryoblast to megakaryocyte
• megakaryocyte are giant cells that form demarcation channels that fragment into protoplatelets and single platelets
• looks like tentacles before fragment

Cartilage Compisition 

• 40% collagen II 
• 60% proteoglycans
• gel like substance
• Avascular

Bone Compisition

• 50% (95%collagen I, 5% GAG)
• 50% Ca-Po4 Crystals (calcification)
• rigid

SOX9

• made in cytosol
• transcription factor that differentiates mesenchymal cells into chondroblasts
• then differentiates into chondrocytes
•  ainly for Type II collagen Synthesis

Perichondrium

• layer of dense connective tissue that acts as fibrous sheath surround cartilage
• outer fibrous(type I collagen)
• inner chondrogenic layer(not fully differentiated chondrocyte with lowwer expression of SOX9)

Apositional Growth

• when chondroblasts cells in chondrogenic layer differentiate into chondrocytes

Interstitial Growth

• when cells with in matrix divides to form more chondroctyes (mitosis)

Hyaline Cartilage

• C shaped cartilage
• has perichondrium
• blood vessins in perichondrium(fibrous layer)
• isogenous groups is several cells together
• both apositional and interstitial growth

Teritorial and Interteritoral Matrix

• teritorial is matrix closely attached to chondrocyte
• interteritorial is one farther away from cell

Elastic Cartilage

• has perichondrium
• have both growths (apositional and interstitial)
• have elastic fibers interweaved(sometimes stained red)
• type II collagen fibers
• can be found in ear

Fibrocartilage

• interstitial growth
• type I collagen(mainly)
• intervetebral disks
• chondrocytes in parallel rows (fewer of these)
• lacks perichondrium

Lucanae

• space around cell that chondrocytes sit in
• not a actual real thing but found in imaging

Rheumatoid Arthritis

• cartilage disease
• inflamatory joint disease or result of autoimmune reaction
• when cartilage is lost bone rubs against bone 
• pannus is accumulation of inflamatory cels

Compact Bone

• dense and cortical bone
• periastium(outer fibrous), inner ossigenic
• collagen I fibers organized in multiple layers
• Haversion systems
• endosteum
• outer and inner circumferential lamellae

Haversion System

• organization of collagen in bone
• haversion canal is between three layers of collagen running parallel with collagen and holds blood supply
• blood enters from volksmanns canal that is perpendicular 
• nerves also use these canals

Endosteum

• extremely thin connective tissue layer linning bone marrow space
• contains endosteal cells
• have tendency to differentiate into bone cells called ossteoblasts

Trabecular Bone

• also known as spongy or cancellous
• space filled with bone marrow cells 
• found after endosteum layer?
• cells here make osteoid that is calcified to become full bone

osteoblasts

• bone forming cells
• mostly in one layer but proliferate when there is a fracture
• differentiated from endosteal cells

osteoid

• unmineralized bone matrix
• first thing made in bone formation
• w/ time beocmes mineralized 
• formed from ossteoblasts in trabecular bone

Osteoclasts

• multinucleated cells that degrade bone marrow 
• resorb(degrade)bone as fast as it is made until you get older and bone production slows down
• forms ceiling zone and attaches to bone with integrins
• membrane develops ruffled border
• very acidic and brought i by endocytosis 
• puts calcium into blood and reacts to calcium levels

Canaliculi

• channels osteocytes use to connect to each other with processes and gap junctions
• nutrients is exchanged through them so that cells further away from blood supply can be nourished

Osteoclast Differentiation Regulation

• osteoblast secretes macrophage colony stimulating Factor(M-CSF) after being affected by parathyroid hormone (also causes production of RANK-L
• these bind to monocyte and cause differentiation to macrophages
• RANK-L on osteoblast then makes contact with RANK on macrophage/osteoprecurson 
• fuse to form resting osteoclast 

Intramembranous Osteogenesis

• bone tissue is formed directly in primative connect tissue
• uses mesenchyme cells that differentiate to osteoblasts

Endochondral Osteogenesis

• bone tissue replaces a hyaline cartilage template
• first cartilage made from inside out by chondrocytes
• chondrocytes then give off calcium that calcifies the cartilage matrix in development (turns black in slides)
• calcium starves chondrocytes that then give off VIG-F before dying
• this brings in vasculature
• Perichondrium becomes periosteum
• undifferentiated chondrocytes become growth plate
• osteoclasts chew upp calcified cartilage and it is replaced with trobecular bone

Growth Plate

• resting zone
• proliferation zone
• hypotrophic zone
• calcified zone
• ossification zone

Indian Hedge Hog (IHH)

• produced by proliferating chondrocytes
• stimulates parathyroid hormone relating protein(PTH-RP)
• this stimulates chondrocyte proliferation and inhibits differentiation into hypertrophic condrocytes
• hypertrophic chondrocytes secrete typeX collagen, marker of terminal differentiation and vascular endothelial growth factor (VEGF)
• inducer of vacular invasion^

Fracture Repair

• inflamation(10%)->reparative(40%)->remodeling(50%)
• stimulates intermembrous and endochondral bone growth at same time(forms callous)
• osteoclasts then come in and remodel

Osteopetrosis

• increase in bone mass
• defective bone reabsorption
• failure in development of bone marrow
• osteoclasts dont work well
• splenomegally 
• platelet formation
• kids dont usually last long

Cleidocranial Dysplasia

• autosomal dominant skeletal 
• cause by mutation in CBFA-1(RUNX2) on chromosome 6
• osteoclast specific
• defective development of cranial bones and complete or partial absence of collar bones 
• cartilage only in KO animals(no bone)
• scoliosis also possibility

Fibrodysplasia Ossificans Progressve (FOP)

• rare autosomal dominant genetic disorder
• sporadic cases
• gene unknown
• progressive endochondral ossification in skeletal muscle, tendon, and ligament
• small trauma causes bone formation in places it shouldnt (like on muscle)