2. CARTILAGE & BONE
• Cartilage & bone are examples of specialized
connective tissue
• Both originate from mesoderm and
mesenchyme
• The major difference is that cartilage is
avascular while bone is vascularized
• Cartilage contains an antiangiogenesis factor
that prevents invasion of the tissue by blood
vessels
3. CARTILAGE
• Like all connective tissue, cartilage is composed of
cells, intercellular space called ground substance or
intercellular matrix and fibers – (collagen)
• The cells of cartilage are chondrocytes
• Chondrocytes originate from stellate shaped
mesenchymal cells.
• Mesenchymal cells round up and differentiate into
chondroblasts
• Chondroblasts synthesize the intercellular matrix
4. CARTILAGE
• When chondroblasts surround themselves
with the intercellular matrix, they become less
active and are called chondrocytes
• In fact, when the chondroblasts become
entrapped in small areas of the intercellular
matrix called lacunae – literally small lakes
5. Appearance Of Cartilage
Consists of round cells suspended in an
extracellular matrix
When fixed, round cells shrink and pull away
from matrix
Resultant “empty” space is called a lacuna,
appearing as a halo or crescent around the
remnants of the cell
Avascular
6.
7. Cartilage Types
•Cartilage is classified by the components of the matrix
•Hyaline (very smooth like a lake)
• no apparent fibers in the matrix
•eg. articular cartilages
•Elastic
•presence of elastic fibers in the matrix
•eg. pinna of ear
•Fibrous
presence of an abundance of type I collagen
bundles
eg. intervertebral discs
8. Cartilage Matrix
•Contains:
•hyaluronic acid
•chondroitin sulfate
•keratan sulfate –
•elastin in elastic cartilage
•type II collagen
•type 1 collagen in fibrocartilage
9. CARTILAGE MATRIX
• The extracellular matrix consists of fibers and
an amorphous ground substance
• Fibers are collagen Type II, elastic and reticular
• Ground Substance is composed of GAGs of the
proteoglycans
• Hyaluronic Acid
• Chondroitin sulfate **
• Keratan sulfate
10. Cartilage Growth & Formation
Interstitial
Chondrocytes divide
secrete matrix, and
are pushed apart by the matrix
A positional
catilage surrounded by perichondrium
innermost layer of cells = chondroblasts
secrete matrix materials which are added
on to edge of existent cartilage
11.
12.
13. GROWTH OF CARTILAGE
• Interstitial Growth – literally from within –
chondrocytes undergo mitosis within the
lacunae. There are long rows of chondrocytes
formed called isogenous clusters. Growth in
length of a piece of cartilage is by interstitial
growth
• Appositional Growth – New cartilage cells and
interstitial matrix are added onto the surface
of a piece of cartilage
14. GROWTH OF CARTILAGE
• Appositional Growth continued –
• Cartilage is covered by a connective tissue investment called
the perichondrium
• The perichondrium consists of two layers, a cellular layer
immediately adjacent to the piece of cartilage & a fibrous
layer located more superficially
• The inner cellular layer contains undifferentiated
mesenchymal cells that continue to differentiate into
chondroblasts and slowly add themselves and the matrix that
they produce to the surface of the piece of cartilage
• Blood vessels contained within the perichondruim represent
the source of nutrients that diffuse through the ground
substance to maintain the chondrocytes
15. CARTILAGE MATRIX
• The highest concentration of newly synthesized
GAGs is in the matrix immediately surrounding the
chondroblast or chondrocyte
• Bound Water – Chondroblasts and chondrocytes
receive their nutrients by diffusion through the
water component & if this life line is compromised,
the cells will die
• Because cartilage can do quite well in an avascular
environment, when a piece breaks off, it has no
trouble surviving and can live for years. It has to be
removed surgically
24. CALCIFICATION OF CARTILAGE
• As we shall see in a later lecture, a normal
process called endochondral ossification in
hyaline cartilage models of the long bones in a
fetus and in an area of bone called the
epiphyseal growth plate is a mechanism of
bone formation.
• For now, we shall just look at bone and
compare it to cartilage
25. TERMS
Macroscopic
Compact - solid chunk of bone
Trabecular = Spongy = Cancellous
meshwork of bony spicules
Microscopic
Immature = Woven – all bone starts out as immature
irregular arrangement of fibers in matrix
Mature = Lamellar
layered arrangement of fibers in matrix – tree trunk
26.
27.
28.
29. BONE
• Again like all connective tissue, bone consists
of cells, fibers and intercellular matrix
• Bone like cartilage is invested with a
connective tissue covering called the
periosteum.
• The periosteum contains an outer fibrous
layer and an inner cellular layer
30. BONE
• Within the inner cellular layer, there are small spindle-shaped
cells (mesenchymal cells). These are the osteoprogenitor cells.
• Within the inner aspect of the fibrous layer, there are
osteoprogenitor cells.
• Osteoprogenitor cells and osteoblasts occupy this layer and
it is called the osteogenic layer.
• There are also osteoclasts present in the osteogenic layer.
• Osteoprogenitor cells can undergo malignant transformation.
This disease is osteogenic sarcoma.
31. BONE CELLS
• Osteoblasts – differentiate from the mesenchymal
cells but UNLIKE the chondroblasts, osteoblasts
retain their stellate shape and are found on the
surface of a developing spicule of bone
• Osteoblasts make collagen Type I fibers and ground
substance
• Ground Substance contains GAGs, glycoproteins and
osteonectin which anchors mineral components to
collagen fibers & osteocalcin, a calcium-binding
protein
32. BONE CELLS
• Immature bone (before it is calcified) is called osteoid and
consists of collagen fibers and ground substance
• Mineralization involves deposition of many different minerals
to hydroxyapatite crystals Ca 10(PO4) 6(OH) 3
• Vitamin C is necessary for the osteoblast to synthesize
osteoid, i.e. make collagen and is also necessary for fracture
repair
• Vitamin D is necessary for proper intestinal absorption of
calcium, defect results in rickets in children and osteomalacia
in adults. Excess causes bone resorption
• Vitamin A deficiency inhibits bone formation and growth
while excess causes a faster rate of ossification of the
epiphyseal growth plates. Both deficiency and excess cause
small stature
33. Mineralization of bone
Incresed concentrations of Ca and PO ions in the
local matrix are brought about by:
binding of Ca by osteocalcin increases local
concentration
osteoblasts stimulated to secrete alkaline
phosphatase
alkaline phosphatase => increased Ca
accumulation
34.
35. BONE CELLS
Osteocytes – As osteoblasts make and secrete
osteoid around themselves, they get trapped
& surrounded by matrix (like falling into
cement with arms and legs extended). Since
they retain their stellate shape,the matrix
hardens around the cytoplasmic processes
forming tiny tunnels called caniculi where the
cell processes remain
36. BONE CELLS
• Once the cells are trapped in their lacunae, they are called osteocytes
• The cytoplasmic processes of osteocytes communicate with each other
within the caniculi via gap junctions
• The osteocyte is quite metabolically inactive although some activity does
occur
• Osteocytes occupy the most but not the entire lacuna
• They have densely stained small irregular nuclei
• Osteocytes in their lacunae are surrounded by extracellular fluid called
“bone fluid”
• May be different composition from extracellular fluid of other tissues
perhaps due to surface osteocytes & osteoblasts forming some type of
“membrane” or barrier that separated bone fluid from other tissue fluids
37. BONE CELLS – HORMONAL INFLUENCES
• Hormonal control of Calcium Homeostasis
• In times of low plasma Calcium, parathyroid hormone is released from the
parathyroid glands
• Parathyroid hormone interacts with receptors on osteoclasts and
osteocytes to cause calcium to be released from bone – done through
mediation of osteoclast-stimulating factor. Excess PTH resulte in bone
being more susceptible to fracture
• Calcitonin- produced by parafollicular cells of thyroid - when blood levels
of calcium are normal or high, calcitonin is released from the thyroid gland
causing calcium to be absorbed and deposited into bone – does so by
eliminating the ruffled border of the osteoclasts
• Pituitary Growth Hormone – stimulates overall growth – epiphyseal plates.
Overproduction results in gigantism and deficiency in dwarfism
38. BONE CELLS
• Osteoclasts – these are derived from the peripheral blood monocyte and as such
are part of the monocyte phagocyte system
• Large, multinucleated,giant cells formed by the fusion of several monocytes
• Major resorbers of bone matrix
• Found in depressions on the bone surface called Howship’s lacunae
• Contain a ruffled border on the resorptive surface, many mitochindria, Golgi
bodies, vesicles & RER
• Clear Zone surrounds the ruffeled border and contains microfilaments which help
osteoclasts maintain contact with the bony surface and also isolates the
osteoclastic activity
• Vesicular Zone – exocytotic vesicles that transfer the lysosomal enzymes to the
Howship’s Lacula & endocytotic vesicles that transfer degraded bone products
from Howship Lacula to the ingerof the cell
• Basal Area- located on the side of the cell opposite the ruffled border – contains
most of the organelles
Non-dividing but DNA synthesis does occur
39. Cells of bone
Osteoprogenitor cells
derived from stem cells of mesenchyme
triggered to become osteoblast
Osteoblasts
appears as a single layer of cuboidal cells lying
on surface of developing bone
exocytose alkaline phosphatase rich, membrane
bound matrix vesicles that are involved in
mineralization of the matrix
40. Cells of bone (continued)
Osteocytes
mature bone cell trapped in lacunae in matrix
processes contact those of other osteocytes and
osteoblasts, joined by gap junctions
Osteoclasts
large, multinucleated cells found in depressions
on the surface of the bone
cells release hydrolytic enzymes that degrade
the bone matrix
41. BONE RESORPTION
• Osteoclasts secrete acid – decalcifies surface
layer of bone
• Acid hydrolases, collagenases degrade the
organic portion of bone
• Osteoclasts resorb the organic and inorganic
residues of the bone matrix and release them
into connective tissue capillaries.
42.
43.
44.
45.
46.
47.
48. Lamellae
Circumferential
lining or circling the marrow or outer
surface of the bone respectively
Concentric
arranged in concentric circles around the
Haversion canal
Interstitial
short arcs in spaces between Haversion
systems
49. COMPACT BONE
• Outer & Inner circumferential lamellae are produced
by the periosteum and endosteum and encircle the
outer and inner aspects of the bone
• Haversian lamellae are found between the outer and
inner circumferential lamellae
• Haversian lamellae form concentric rings around a
small canal containing blood vessels and nerves – the
canal is called the Haversian Canal and represents
the vascular system of the bone
50. COMPACT BONE
• One Haversian system is also known as an osteon
and is separated from other Haversian systems by a
cement line
• Each lamella is connected to another by the
canaliculi and ultimately with the periosteum and
endosteum
• In this manner the innermost osteocytes maintain a
connection with the circulatory system. If the system
breaks down, the osteocytes die and so does that
portion of bone
51.
52. SPONGY BONE
• This is also mature bone
• Unlike compact bone, spongy bone is merely
spicules covered by endosteum
• Bone marrow is present between spicules
• Found in flat bones of skull
Jelly like and a foam like. Blood is window to whats going on in bodyHigh oxiproline in urine means what.Low RBC – anemiaClinical… bone level too high too low.
Cartilage is avascular.
Chondo = cartlageBlast is undifferetaited cell that has capacity to divide and doa bunch of stuff. Too much blast cells is not a good thing
Making intercellular matrix. In connective tissue, cells were scattered. But here as they push apart they get trapped in a depression – lacunae, very distinct to indetify. Once in here they become chondrocytes.
A is extra cellualr tissueB is thelacunaue… holes are lacunaueShrunken dot in the middle is the chondrocyte. Look at the 3 in a row.. Area wherchondrocytes are dividing. Interstitial growth
Cartilage = HEFEar is flexible so elasticFibrous where you need resistance to stress… main place is intersdiscs
Sulfate highly charged and they hold water.. Therefor very flexible bc has high water content.
Even though pushed apart your going to see lines of cells. Interstitial. Outer layer in fibrousInner is undif cells and chondroblasts. Push outwards.. That’s how they grow
Ch is lacunea, bottom is fibrous layer, cells has big nucleus,, its making intercellualr matrix and push furhter and further away from each other. notice the 3 chondrocytes lined up.. Interstitial growth is the division of the chondrocytes… Bottom bottom is fibroblasts which come from mesenchyme. P for perichondorium
Perichondrium is the bottom p.. White area is where new chondroblasts are becoming chondrocytes… deeper stain is chondrocytes… rows are called isogenis clusters. Never see isogenis clusters in bone. Only in cartilage
Mitotic division within lacunaeGrowth in width appositional.. Growth in length interstitial
Things diffuse through watery intercelleluar matrix
Nuetrophils move into damaged area and gobble things up as well as macrophages. Macrophage come from blood cells. Cart is avascular. So if you break chunk of cartilage these cells arent coming in there to clean it or attack.. Must be removed surgically if bad cartilage infected. Cartilage avascular
This is cartilage. Spread apart cells in lacunae. Dot is shrunken chondrcytes.No fibers so its hyaline - smooth lake
Hs fibers… so its fibrous cartilage.. Def not a smooth lake
Elastic cartilageStains blueish? Notice the dark distinct elastic bands
Cartilage - fibrous
Isogenis clusters so its cartilage. Has fibers.. Fibrous cartilage.. Again. it doesn’t look like a smooth lake
Fibrous cartilage.. Isogenis clusters chondrocytes.Type 1 collagen fibers, lots of it
Zoomed in.. Lots of collagen
Bone is little more complex
Now were going to compare bone to cartilage. Compact and trabceluar are mature bone.
Shaft is long part and is compact… all is mature bone… ends are trabecular and spongy
Compact is outside… right side is trabecular.. Very easy to see. Inside eeventualy develops into mature bone
Outside is compact
Osteum = boneInner layer will have osteoblast . Made from primitive mesenchyme…. Pushed out. Trapped in lacuna..
Mesen . Osteoprogenitro. Osteoblast. And osteoclast= final product and is a macrophage.
Type 1 forms a meshwork. Holes. Bone is vascularHoles is where calcification takes place.Vesicles occupy the holes in the spongy bones. Contain chemicals to aattract calcium phosphate and GAG. Very hard so no diffusion. Not wateryOsteoblast make matrix type 1 collagen fibers. cell retain shape. So osteocyte remains stellate shapePeriosteum (bottom layer) will have lots of vascules. But osteocytes need nutrients. One communicates with other via gap junction within a deep lacunaeOsteoide – immature bone not yet calcified. Need vitamin c for effective cross linking of callogen , if not then you will have deformed bone. Sailors had bone defects after cruise. Cure was limes
Osteocyte.. When trappe din lacuna.Chondrocyte.. When trapped in lacuna
Osteocyte are metabolically active
Bone – major storage of calciumWhen calcium gets too high, c cells turn off parathyroid hormone and put calcium back into bone. C cell – calcium homeostasis. C for calcitonin
Osteoclast. Like cleaners.ruffles like octopuses. Attach to bony surface. Contain lysosomal enzymes and degrade the bone.
Stem cells – osteoblast – osteocytesKnow vitamins A D and C and causes of definciency.
Know this cartoon.. Mitochondria.. Needs a lot of energy. Ruffle border.. Right side is the bone. With enough calium in bone it stops the mobilzation of calcium (also on the right)
Know this.
Arrow is pointing to osteoclasts.
Forget this. skipped
Mature bone.. No pattern .. Lighter area is decalcified. Circular thing on top is a lamella araranged around a abversino canal … circle is lamellar bone
Bone when it is not decalcified… osteocytes appear dark.. Canaliculi are the lines coming out of them and they are used in communication with each other. Compact bone
Structures that bear weight of entire building = same principal of the bone.
Picture same as 5 slides back. Blood vesel enters the bone and hits the hoversioncanals.from top view hoversion systems travel through entire length of the bone.
immature bone.
Capilaries inside hoversion canal. Dark dots are ostecytes in lacuna. Hoversion system is the entire citcle. Osteocytes all communicate with each other and ultimaltely the hoversion canal. (ges closer and closer)… then eventuauly down the canal to the peristeum. When osteocytes die the bone dies
Osteon = one hoversion system
Canaliculie for communication
Osteon in decalcified … cant stain a bone, cant get dye in
This is not the for picture …Immature bone = woven bone
Bone is very light but very strong. Compact bone along the shaft of the bone.
Fracture repair . Area of fracture has a clot. Will see a small black and blue..First – blood clot bc disrupted ciculation in hoversion system and osteocytes will die. And that portion of bone will die.. Still have periosteum. Fibroblast from periosteum invade clot and make grandulation tissue (that’s why u line up bone ) to bridge where the clot is. Hemorage is site of blood clot. Callous becomes cartilage and later replaced by bone. Need calcification (to harden it). Get spongy bone and then eventualy compact bone. Will only happen once patient starts walking (stress on the area)
Bone formation. Cartilage model in the embryo… bottom left is how we are born .First blue area on top are blood vessels and creat beginning of the shaft. Bone grows from the blue lines (growth plate) . Maintained from embryonic state up until the end of puberty. Next few slides on growth plates. shaft will be compact lamellar bone. Notice the artery and vein
This is Whats going on at growth plate. This is still cartilage . Pushes ends apart (interstitialy)Noticeisogenis clusters. (interstitial growth) area of proliferation. Then mitosis stops.. Cells get larger in the lacuna(hypertrophy). Chondrocytes will be starved of nutrients (will die) and be replaced by osteoblasts (which will make these bony spicules. Osteoblast and clasts lining at bottom