CTB: Cartilage, Bone, Diffusion and Osmosis

thin frictionless tangentially produces lubricin perpendicularly, better tangential strength

Articular cartilage is very (thin or thick), require for (frictionless or friction) motion, 2 zones - Superficial Zone: collagen oriented (perpendicular or tangentially), produces L_. - Deep Zone: Collagen oriented (perpendicular or tangentially) for (better or worse) tangential strength

Inorganic Salts! Na+ mostly, b/c attracted to negative charge of proteoglycans. then water follows Na+ to proteoglycans.

Cartilage. what are specialized non-protein molecules that comprise of cartilage? (mostly what ion?) Why?

glycosylated GAG Aggrecan! large proteoglycan Core PROTEIN + (CS/KS side chains) Chondroitin Sulfate (CS) and Keratin Sulfate (KS) side chains - collection of aggrecans noncovalently attached via link protein to a Hyaluronic acid (HA) backbone

Cartilage: Proteoglycans Heavily (hydroxylated or glycosylated) with _ side chains. Many different type but A_ is most important. - What is a proteoglycan aggregate?

Sox9 Type II Cartilage gene product Sox 9 is nuclear transcription factor than up regulates synthesis Type II cartilage

Chondrogenesis _ gene required for Type _ Cartilage synthesis and differentiation

Mesoderm gives rise to Mesenchymal cells -> chondroid precursor cells-> chondroblasts->chondrocytes Less active!

Chondrogenesis M_ cells-> C_ (pre or post) cursor cells-> C_-> C_ Chondrocytes are more or less active than chondroblasts?

Mesenchymal BMPs

Chondrogenesis begins with compaction of loose _ cells, the growth factors _ are key to this.

mesoderm (which gives rise to MESENCHYMAL cells, which are multi potent) ectoderm

Chondrogenesis. origin M_= most chondrocytes in body, which give rise to _. and E_= chondrocytes in head region

majority Endochondral

Early fetal life, cartilage makes up (minority or majority) of skeleton and slowly replaced by (E_ bone formation)

Mesoderm Mesenchymal mutli many Chondrocytes Osteoblasts Muscle cells Fibroblasts Adipocytes

Osteoprogenitor Cell Differentiation. Mesenchymal stem cells originate from the M_ . M_ stem cells are (multi or toti) potent, which means they have to potential to differentiate into (one or many) different cell types. like C_cytes O_blasts M_ cells F_blasts A_cytes

many osteoblasts Core Binding Factor Alpha-1 CBFA1) and BMP!

Osteoprogenitor Cell Differentiation. potential to make (one or many) different cell types BUT driven toward (osteoblasts or chondrocytes) formation by C_ B_ F_ A_-(1 or 2) (CBFA1) and what other molecules? (hint, related to TGF beta) Other factors are RUNX2, RUNX3, Osterix, PPAR-gamma, WNT signaling pathway (beta catenin,sclerostin, DKK-1)

Osteoclasts

Patient on left present with increased bone density, shortened limbs, spontaneous fracture, and multiple deformities. A biopsy of patient on left is most likely to show an absence of which of the cell types which control bone formation and resorption?

recurrent nose auricular narrowing

Relapsing Polychondritis, rare autoimmune disease (unknown etiology) - characterized by (constant or recurrent) episodes of inflammation affecting the cartilage of 1) N_ cartilage 2) A_ cartilage (ear is floppy) 3) Tracheobronchial involvmenet. (widening or narrowing) of intrathoracic trachea

Sox9 (a nuclear transcription factor) Cartilage

Sox9 gene encodes _ and is critical in _ differentiation

early in Mesenchymal Cartilage

Sox9 gene expressed (early or late) in M_ cells and is critical in C_ differentiation

Hyaline, Elastic, Fibrocartilage

3 types of cartilage

Elastic Cartilage

Type of Cartilage has numerous elastic fibers as well as type II collagen

Elastic cartilage

Type of Cartilage. Found in wall of Eustachian tube, the ear, the epiglottis, and some laryngeal cartilages

Fibrocartilage (more)

Type of Cartilage. Has type I collagen in addition to type II (less or more tensile strength)

Fibrocartilage

Type of cartilage. Found in intervertebral disks, menisci of the knee and ligaments/tendons, pubic symphysis

Fibrocartilage

Type of cartilage. No Perichondrium

Fibrocartilage

Type of cartilage. less water than other cartilage

Osteoprogenitor Cells Osteoblasts Osteocytes Osteoclasts

What are the four bone cells? O_p_ cells, O_, O_, and O__

Osteoblasts, osteocytes, as well as osteoclasts.

What cell types are specific to bone?

- cell-matrix interactions - growth/differentiation factors - environmental factors

What controls chondrocyte and cartilage formation?

The contain blood vessels and nerves and are carrying them from the periosteal and endosteal regions to the Haversian canals

What do the Volkmann's (perforating) canals contain and what is their function?

Osteon

What is name of concentric lamellae of collagen fibers in an ossified matrix, with a circular profile at the center?

Haversian canal (osteonal canal) Blood vessels, normally small arterioles and venues, and nerves

What is the circular profile in the center of the osteon and what structures can be found there?

Chondrocytes

What is the name for less active cartilage cells where two or more cells occupy each lacuna of cartilage?

- hydroxyapatite Calcium, Phosphates, and hydroxyls groups together - Gives rigidity to bone and serves as a source of calcium and phosphate for the body

What key mineral is a method of obtaining a section of bone without de-mineralizing it preserving? - What is the role of this mineral when it is incorporated into bone?

Elastic cartilage contains elastic fibers (collagen) not seen in abundance in the other cell types

What type of cartilage forms the epiglottis? - Compare the properties of this cartilage type with the other types of cartilage. (what does it have an abundance of)

Hyaline Type II Aggrecan GAGs Glycoproteins

What type of cartilage is found in the trachea and what are its components? The trachea contains _ cartilage whose major feature is type (I or II) collagen fibrils and A_, its most important proteoglycan. But is also contains G_ (turgidity) and multi-adhesive G_

Hyaline cartilage

type of cartilage found on articular surfaces of bone at joints and in nose, larynx, trachea and bronchi

initial puberty

type of cartilage. Forms the (initial or final) model for subsequent development of most bone (allows for growth up to _)

Hyaline Cartilage

type of cartilage. Glassy and translucent (sulfated GAGs hide type II collagen)

COMP Cartilage Oligomeric Matrix

Cartilage. _ stabilizes collagen network

Lubricin

Cartilage. _-lubricates joints

organized vascularized appositional Osteocytes Osteoglasts Osteoblasts Hydroxyapatite

Bone Highly (organized or disorganized) (vascularized or avascularized) (appositional or interstitial) addition of cells, which are O_cyte, O_clasts, O_blasts and addition of ground substance (part of ECM) in growth Mineralization of its matrix, Calcum phosphate turns into -> H_ crystals.

osteoid. Canaliculi gap junctions

Bone Cells . Osteocytes Trapped in O_ Tiny extensions of cytoplasm extend through C_uli and form what type of cell to cell connection with other osteocytes?

osteoblasts osteocytes

Bone Cells. Bone ECM comprised a lot of Osteoid is secreted by (osteoblasts or osteocytes) and become (osteoblasts or osteocytes) when surrounded by ECM

Osteoid, Type I Glycosaminoglycans hydroxyapatite osteoid structure Osteoid osteocytes

Bone Cells. Osteoblasts - Synthesize components of O_, such as Type (I or II) collagen, G_s, and Osteoid structure promotes formation of _ crystals. - adhere to surface and secrete O_ in a polarized (appositional growth) manner - Some become surrounded by O_ and become trapped and transform into (osteocytes or osteoclasts)

breakdown actin acid V type H+ degradative phosphate Howship's Lacunae monocyte small multinucleate

Bone Cells. Osteoclasts. - Responsible for (breakdown or development) of bone matrix by forming tight pocket with bone surface (_ filament dependent), secrete (acid or bases) by V-type (H+ or OH-) pump, secrete (degradative or anabolic) enzymes, remove calcium and P_ (demineralize, put into blood), carve out pockets known as H_ship's Lacu_ - (B-cell or monocyte) lineage - (small or giant) (uni or multinucleate) cells

Osteoid Mineral Osteoid - 50% bone volume, 25% bone weight Type I collagen fibers unmineralized, proteoglycans Mineral - 50% of bone volume, 75% of bone weight

Bone Extracellular Matrix. Give the two components O_ and M_ - O_ (50 or 25%) of bone volume, (50 or 25%) of bone weight. 90-95% of type (I or II) collagen fibers (mineralized or unmineralized) proteins, carbohydrates, Proteo_, and Lipids - M_ (50 or 75%) of bone volume, (50 or 75% ) of bone weight

development of skeletal system Endochondrial Intramembraneous

Bone Formation. Modeling- (development or degradation) of skeletal system - What are two forms of modeling? E_ and I_ bone formation

Cartilage Periosteal Cartiage Diaphysis hyper Bone Marrow Cartilage Primary, Ossification Metaphysis Epiphysis avascular vascular Vascular Endothelial Growth Factor Matrix Metalloproteinases long hyper Periosteal Intramembranous 6. proximal 7. secondary, ossification, proximal epiphysis 8. distal, Epiphyseal Cartilage 9. proximal, disappears 10. proximal, disappears, cessation of growth.

Bone Formation. Modeling. Endochondral 1. C_ model laid down (hyaline surrounded by Perichondrium) 2. P_ collar of bone (calcify C_ matrix) forms around D_ (shaft ) by (Hypo or hyper) trophy of chondrocytes 3. Blood vessels and CT cells erode and invade leading to primitive B_ M_ cavity - C_ remains at bone ends - (primary or secondary) center of O_ develops - M_- spicules of bone surrounded by osteoblasts (bone at ends of developing marrow cavity) - E_= the end of the bone *Replacement of (vascular or avascular) bone by (avascular or vascular) bone via hormones VEGF and MMPs (write out names and their other functions) -- chondrocytes align in (long or short) rows along axis of the bone. --Chondrocytes (hyper or hypo) trophy and (die or live) --Osteoblasts follow 5. P_ bone continues to form as a result of I_ ossification 6. Blood vessels invade the (distal or proximal) epiphyseal cartilage 7. (primary or secondary) center of O_ established in (distal or proximal) (diaphysis or epiphysis) (around birth) 8. Similar epiphyseal ossification center forms at (proximal or distal) end of bone (known as E_ C_ (Growth Plate)) is formed between each epiphysis and diaphysis 9. (distal or proximal) epiphyseal cartilage (disappears or reappears) 10. (distal or proximal) epiphyseal cartilage (disappears or appears) with (proliferation or cessation of growth)

cartilage (hyaline surrounded by Perichondrium) precursor extremeties axial skeleton

Bone Formation. Modeling. Endochondrial formation meanest that (cartilage or epithelial) model which is (H_ surrounded by P_) serves as (pre or post) cursor/template. Endochondrial formation forms the (intermediaties or extremities) and weight bearing (axial or appendicular skeleton)

no cartilage precursor - flat face, skull, clavicle, mandible small condensed messenchymal trabiculae mesenchym trabiculae dense

Bone Formation. Modeling. Intramembranous (cartilage or no cartilage) precursor - (long or flat bones) of the F_, S_, C_ and M_ (jaw). - Durign Embyogenesis, flat bones begin as (large or small) foci of (scattered or condensed) (epithelial or mesenchymal) cells - When they are induced to grow, they form T_lae with intervening M_ (secondary or primary) spongy bone)) - T_lae fuse and form (loose or dense) cortical bone

PTHrP (parathryroid hormone related Protein) PTHrP-> premature differentiation -> leads to brachydactyly Indian Hedgehog Periarticular

Bone Formation. Modeling. Molecular Control. What hormone causes chondrocyte proliferation and (hyper or hypo) trophy? P_ - If you block this hormone (P_)-> (mature or premature) differentiation-> early closure, long bones shorter-> leads to B_ctyly - PTHrP is UPregulated by I_ H_ (ihh) - PTHrP is expressed in P_ region

continual PTH (parathryoid hormone) and Vitamin D

Bone Formation. Remodeling: lifelong, (intermittent or continual) process of skeletal refinement. What hormone and co-factor stimulates osteoblasts to secrete factors (M-CSF) that cause osteoclast formation?

support, protection caclium, phosphate regulate flux Bone marrow

Bone Function - Structural S_ and P_ - Storage site for C_ and _P (regulate or not regulate) flux of those ions in and out of blood. Homeostasis. - Houses B_ M_

dense bone compact layer outside just below periosteum

Bone Structure. (dense or loose) bone (compact) - (loose or compact) layer on the (inside or outside) of the bone (just above or below) periosteum

lacunae within bony matrix contain a bone cell (osteocyte)

Bone Structure. L_nae (within or outside) of bony matrix contain a bone cell (O_cyte) (in red)

mature Osteons Haversian osteonal long does! Volkman's adjacent parallel adjacent

Bone Structure. Osteons are - (mature or immature) bone composed of cylindrical units called O_ or H_ systems. - concentric lamellae of bone surrounding an O_ (Haversian) canal along (long or short) axis of the bone. (does or does not) contain nerve and vascular supply - V_ canals connect (distant or adjacent) osteonal canals - Collagen laid (parallel or perpendicular) in a given lamellae, each (adjacent or distant) lamellae has different direction (strength)

Periosteum dense osteoprogenitor less

Bone Structure. P_ coverts bone surface (except articular) Outer Layer: Sheath of (loose or dense) connective tissue Inner Layer: More cellular layer with (osteoprogenitor or osteoblasts) (more or less) defined in non-growing bone

Hematopoetic tissue fat yellow

Bone Structure. Within bones is the marrow cavity which contains marrow that is composed of H_ tissue, and becomes filled with (sugars or fat) in late life (yellow or green) marrow

Trabecular

Bone Structure. _ Bone is a Sponge-like meshwork of trabecular

RANK RANKL generation increased OPG osteoblasts osteoclasts

Bone cells. Osteoclast precursors have the R_K receptor which the R_K ligand (_) on stromal cells bind to resulting in (generation or degradation) of more osteoclasts, leading to (increased or decreased) bone reabsorption. BUT _ is a decoy receptor produced by (osteoblasts or osteoclasts), prevents (osteoblasts or osteoclast) differentiation.

Endosteum one osteoprogenitor gives rise to osteoblasts Periosteal

Bone structure. E_- lines compact bone facing marrow cavity and the trabeculae of spongy bone - (one or two) layer thick - (contains osteoclasts or osteoprogenitor) cells -> osteo(blasts or cyts) and bone lining cells called P_eal cells

Canaliculi

Bone structure. Small tunnels. Give Name C_i

insoluble, Type II 15% tensile strength (triple helix)

Cartilage Collagen: major (soluble or insoluble) fibrous protein in connective tissue. In collagen, type _. _ percent of cartilage volume. It's strong, rigid fibrils give it what?

Collagen, proteoglycans, Water, other specialized molecules

Cartilage Extracellular Matrix Components (give four)

Perichondrium Contains stem cells

Cartilage Growth Cartilage mass is surrounded by _ which contains what type of cells?

balance between cartilage synthesis and degradation

Cartilage Remodeling

MMPs (Matrix metalloproteinases) and (ADAMTs) aggrecanases

Cartilage Remodeling Degradation _ and _ (remove damaged cartilage)

cytokines control MMP production Growth Factors (TGFbeta) control TIMP production BREAKDOWN!

Cartilage Remodeling Regulation cytokines control Growth factors (TGFBeta) control if the amount of active MMP > TIMPs, the connective tissue (synthesis or breakdown) occurs

ECM production by Chondrocytes and tissue inhibitor of Matrix Metalloproteinases (TIMPs)

Cartilage Remodeling Synthesis ECM (production or degradation) by Chon_ and tissue inhibitors of what?

Not efficient (can repair but not effective) Chondrocytes do not migrate Cartilage is avascular, hampers repair effort. - full thickness, heal somewhat if tear extends to vascular supply, replaced cartilage resembles fibrocartilage

Cartilage Repair Efficient or not? Why? Give two reasons What is better, partial thickness cartilage tears or full thickness cartilage tears? Why?

Appositional Growth fibroblast, chondroid Perichondrium may contain

Cartilage _ Growth is when STEM cells differentiate into _ and _ precursor cells from where? The Perichondrium (may or may not) contain blood vessels

Interstitial Growth Lacunae NoT polarized can secrete in any direction

Cartilage _ Growth is when chondrocytes within L_ grow AND continue to produce ECM. (is this production polarized or not? What does this mean?

chondrocytes Lacunae limited Lacunae growth!! 5% Paucicellular 1.

Cartilage cells (C_) are imprisoned within L_ surrounded by ECM. There is (limited or unlimited) amount of cell proliferation in L_. This leads to Interstitial (growth or stagnation). _ percent of mature (P_) adult cartilage is cells. Typical _ # of chondrocyte(s) in a Lacunae but more than one can be there.

avascular (or neurons or lymph) flexible connective tissue of cells (chondrocytes) in Lacunae surrounded by ECM

Cartilage is (vascular or avascular) resilient, (flexible or inflexible) _ tissue of cells (C_) in L_ surrounded by _.

sulfate

Cartilage, proteoglycnas _ groups in CS (chondroitin sulfate) and KS (keratin sulfate) impart negative charge->water trapping

Link Protein

Cartilage. Other Specialized molecules. _ _ stabilizes aggrecan attachment to HA

60 to 80% negative charges on proteoglycans cause water INFLUX acts as CUSHION (compressive properties- spring effect)

Cartilage. Water _ percent of volume - Fixed (negative or positive) charge on Proteoglycans cause water influx - Acts as (rock or cushion) compressive properties (SPRING effect!)

Elastin

Cartilage. _ provides flexibility

Campomelic dysplasia (absence of cartilage in trachea) this is fatal. - skeletal dysplasias (prevent endochondrial bone formation, shott and bowed limbs, club feet)

Defect in Sox9 gene leads to what? C_ D_ (presence or absence of C_ in where?) Is this fatal? Defect in Sox9 gene also leads to what?

a) surface, integrins, tight B) acid, V-Type H+ pump, Carbonic anhydrase, H+, H+, HCO3 Cl-, HCO3- exchangers, opposite, HCO3- C) Cathrin, lysozyme, lysozomal

Describe how osteoclasts function in terms of the following: a) how they create an isolated niche for themselves b) How this niche is acidified c) How acid proteases are released into this space **a) Osteoclasts move along the (surface or inner) bone and settle down, sealing itself to the bone through I_ that bind to vitronectins on the bone surface. This creates a (loose or tight) seal between the osteoclasts plasma membrane and the mineralized matrix of the bone. **B) (base or acid) secretion is mediated by a _-type _ pump at the ruffled border membrane facing the lacuna. Carbonic A_ (CA) in the cytosol supplies the (H+ or HCO3-) to the _ pump and also produces (H+ or HCO3-) as a byproduct. _ exchangers, located in the membrane (opposite or same) to the ruffled border, remove this (H+ or HCO3-) **C) (Calvolin or CLathrin) coated (lysosomes or endoplasmic reticulums) fuse with the ruffled membrane and release the (lysosomal or ER) enzymes into this space.

Yes b/c bone is constantly remodeling through a balance between osteoblasts and osteoclasts.

Do you expect to find osteoclasts in mature bone? Why or Why not?

chondrocytes dispersed matrix metalloproteinases (MMP) chondrocytes

How are cartilage Lacunae formed? (first, what are they?) As newly divided (osteocytes or chondrocytes) produce matrix material, which surrounds them, they become (closed in or dispersed) They also secrete _(__) enzymes that degrade cartilage matrix, allowing the cells to expand and reposition themselves within the growing isogenous group. (chondrocytes or osteocytes) located in lacunae

RANK RANKL increased decreased decreased without increased increased

How could a RANKL mutation cause a presentation where abnormal (left) density of bone and increased stunted growth and spontaneous fractures? (RANK or RANKL) is expressed by osteoclast precursors. (RANK or RANKL) is expressed by osteoblasts and stromal cells. Binding of RANKL to RANK activates NF-kB signalizing, which leads to (increased or decreased) osteoclastogenesis. Mutated RANKL would lead to (increased or decreased) osteoclastogenesis, and (increased or decreased) bone remodeling and reabsorption; bone formation (with or without) ability to reabsorb or remodel would lead to (decreased or increased) density of bone and (decreased or increased) fragility of bone.

Endosteal Periosteal Volkmann's canal Haverisan Canals Osteocytes

How does a solute from the blood vessels reach the osteocytes? Starting with the vessels in the E_ and P_ region, blood flows through vessels in the _ canal to the _ canal and then to (osteocytes or osteoblasts)

Major difference bone is vascular while cartilage is avascular. Bone has continuous supply of blood that travels in small vessels from the endosteal and periosteal regions through the Volkmann's canals to the Haversian canals and then to the osteocytes located there. **THe significance is that bone can enlarge while cartilage is relatively stable in size and metabolically active.

How does the vascular supply of bone differ from that of cartilage? - what is the significance of this difference?

chondrocytes and chondroblasts.

Immediately surrounding the piece of cartilage is a specialized sheath of connective tissue, the P_. Within the perchondrium, notice cells close to the inner edge of the cartilage with large nuclei, these are stem cells. What cell types do these cell types the potential to become?

young apart chondrocytes less

In the periphery of cartilage, individual cells occupy lacunae. These cells can be either chondrocytes or chondroblasts. What is the role of chondroblasts? Chondroblasts are (old or young) cartilage cells that secrete cartilage matrix; they move progressively (closer or apart) as they deposit matrix. When they are completely surrounded by matrix, they are called (chondrocytes or chondroblasts) and are (more or less) active.

damage to articular cartilage. 75 reduction

Osteoarthritis damage to common arthritis affecting _ percent of those above 65. Osteoarthritis patiens suffer pain, (reduction or increase) in range of motion, and disability. Aging cartilage loses many of its properties over time (increase cartilage degradation factors)

ENDOCHONDREAL OSSIFICATION Chondrocytes chondrocytes hyper darker empty death, degeneration of chondrocytes spicules numerous type I eosinophilic has not osteoprogenitor cells (oseteoblast secreting matrix and osteoclasts becoming ensconced in it) osteoclasts MONOCYTES (which are from hematopoietic stem cells) - completely

Steps of bone formation from cartilage! (endochondreal or intermembraneous ossification) 1) (Chondrocyte or osteoblasts) align in long rows (parallel or perpendicular) to the length of the bone 2) (Chondrocytes or osteoblasts) become enlarged and (hypo or hyper) trophy and a (lighter or darker) matrix surrounds them 3) (filled or empty) spaces, due to (proliferation or death, degeneration of chondrocytes) appear between S_ of cartilage matrix 4) (few or numerous) blood vessels penetrate into the developing bone. The young bone matrix (type I or II collagen) is very (basophilic or eosinophilic) because is (has or has not) calcified. 5) Proliferation of (chondroprogenitor or osteoprogenitor0 cells and deposition of bone matrix continues. 6) Simultaenously (osteoblasts or osteoclasts) derived from the (monocytes or basophils) escaping from the blood vessels, degrade the remaining cartilage spicules, which are eventually (somewhat or completely) eliminated.

motion capsule synovial Hyaline Collagen give it its toughness

Synovial Joints are associated with (standing or motion) - They have a joint C_ filled with _ fluid - they contain what type of cartilage? Why is cartilage here tough?

Intima (lining of tissue) Intimal Macrophages Intimael Fibroblasts (produce HA) and lubricine

Synovial Joints. the Synovia I_ is the lining tissue of joint cartilage and has two type of cells. Intimal _ (provide immune response) Intimal _ - produce Hyauloronic Acid (HA) and Lubricin

HA (Hyaluronic Acid) and Lubricin HA protects (viscostity) Lubricin lubricates both provide nutrients to avascular cartilage - comes from interstitial fluid filtered from blood plasma from fenestrated micro vessels located in synovium. YES!

Synovial fluid in synovial joint capsules composed of _ and _ What is the purpose of each? Where does synovial fluid come from? Does synovial fluid provide nutrients and remove waste from avascular cartilage (expedited by mechanical compression)

type II collagen proteoglycans chondrocytes

The extracellular matrix of cartilage is made of type _ _ and P_. They are secreted by C_. ECM also has water, and other specialized molecules

blood vessels and bone marrow reticular cells future blood cells

The spaces between the developing bone spicules are occupied by what? Give two . The numerous cells in the B_M_ are either _ cells or future _ cells.

Osteoprogenitor cells (smaller) and osteoblasts (larger cells)

What type of cells would you expect to find around the trabecular? (two) **What is the role of these cells? What is unique about their growth pattern? Produce (osteoclasts or osteoblasts) which in turn lay down C_ and G_ S_ to initiate bone formation. **They eventually surround themselves with (collagen or bone) matrix and, themselves form part of the trabecular. The blood vessels ar the periphery of the trabecular or pushed (back or forward) and eventually are completely surrounded by O_.

outside, avascular avascular diffusion extra does!

Where are blood vessels supplying nutrients and oxygen to the cartilage located? - Blood vessels are located (inside or outside) of the cartilage matrix, since cartilage is (vascular or avascular) - What is the significance of the location of blood vessels? *Cartilave is (vascular or avascular) and depends on (uptake or diffusion) of material from the (inner or extra) cartilage blood vessels into the cartilage itself. This (does or does not) limit the cartilage size.

Lacunae Caniculi

Where are osteocytes found in the osteon? In the osteon, osteocytes are found in spaces, called _, which confom to the shape of the cell. The extend processes through _ to contact other (osteocytes or osteoblasts)

MONOCYTES, which come from (Hematapoietic stem cells). They are multinucleate cells - fusion of mono nuclear hematopoeitic osteoblasts inhibited, OPG, decoy RECEPTOR inhibitor

Which cells give rise to the osteoclasts? How are osteoclasts stimulated? How are they inactivated? - Osteoclasts are derived from (fusion or separation) of (multi or mono) nuclear (hematopoeitic or mesenchymal) progenitor cells ** Osteoclasts are stimulated by signals from (osteocytes or osteoblasts), namely via the RANK-RANKL signaling system. Theis can be (inhibited or stimulate) by osteoprotegerin (_), which acts as a decoy (receptor or ligand) for RANKL. Lack of available ligand affects the RANK-RANKL signaling pathway and acts as a potent (stimulator or inhibitor) of osteoclasts formation. Most other substances that affect bone growth and resorpton act through the RANK/OPG pathways

NONE!

Which of the following does cartilage contain? blood vessels, nerves, lymphatics (lymph)

Allow processes of osteocytes to contact each other and provide signaling to each other.

Why are caniculi important?

no limiting basement membrane - Subintima lies beneath intima and contains collagen, proteolgycans (PGs) and highly vascularized with fenestrated vessels

Within synovial joints is there a limiting basement membrane? Where does the synovial Subintima lie? What does it contain?

Sox9 gene

_ gene is critical in chondrocyte differentiation