Cartilage Flashcards
Cartilage Properties
- Special class of _____ deposited by chondrocyte cells.
- _____.
- Permeable (conducts nutrients and water).
- Flexible but weight-bearing (resistant to compression).
- Elastic and resilient.
- Resistant to shear forces.
- Slippery (low friction at articular joints).
- Poor _____.
- Can be calcified (functionally or pathologically).
- Evolutionarily _____ skeletal element.
connective tissue
avascular
regenerative capacity
old
Cartilage Properties
avascular > impt for the nutrition of the tissue > diffusion is via _____ within the chondrocytes
flexible > _____
resistant to compression > via _____
chondrocytes = _____ > cannot divide (poor regenerative capacity)
calcification of cart > pathological > depends on the diffusion of _____ > will be impeded by the calcification > degeneration of cartilage and loss of functionality
can be a _____ > shark skeleton; can be calcified to strengthen the skeletal element (very different from how bones are mineralized) (calcification v mineraliziation)
simple diffusion fibrillar collagen (type II) proteoglycans post-mitotic nutrients skeletal element
Composition of Cartilage
• Cells
– Chondrocyte.
• Fibers – Hyaline: • Type \_\_\_\_\_ Collagen – Elastic: • Type \_\_\_\_\_ Collagen • Elastic Fibers – Fibrocartilage: • Type \_\_\_\_\_ Collagen
- ECM:
- GAGs
- Proteoglycans
I
II
I
Cartilage Cells: Chondroblast
- Progenitor of _____.
- Lines border between _____ and matrix.
- Secretes type _____ collagen and other ECM components
chondroblasts capable of _____ (within the perichondrium)
chondrocytes
perichondrium
II
mitosis/division
Cartilage Cells: Chondrocyte
• \_\_\_\_\_ cartilage cell. • Reside in a space called the \_\_\_\_\_. • Clear areas = lipid droplets. • Chondrocytes completely fill their lacunae. • Prominent \_\_\_\_\_. • Synthetically \_\_\_\_\_, secrete matrix.
mature
lacuna
endoplasmic reticulum
active
Cartilage Cells: Chondrocyte
cannot divide more than _____ times at most; essentially they are terminal (fully differentiated)
embedded in the ECM that is deposited by the cells
lacuna = _____
2-3
lake
Cartilage Cells: Chondrocyte
cells have white masses within > chondrocytes are known to store _____ as their source of energy
the lipids are removed during the preparation of the tissue (it used to be lcoated within the white region)
can also accumulate _____; _____ is the most important source of energy
very _____ in terms of secretion > make different types of ECM (territorial/interterritorial matrices)
lipids
glycogen
adipose
active
Cartilage Collagen Fibrils
• Type II Collagen:
• Major fibril-forming collagen in _____.
• Forms fibrils similar to Type I in CT, with lower
_____.
- Type XI Collagen:
- _____ fibril-forming collagen.
- Associated to the surface of type _____ collagen fibrils:
- The ratio of types II and XI determines the _____.
- Type IX Collagen:
- _____ collagen on the fibril surface
- Allows interaction with other _____ components (e.g. chondroitin sulfate)
cartilage
diameter
minor
II
fibril diameter
fibril-associated
ECM
Cartilage of Collagen Fibrils
cartilage is _____ > you can find multiple types of collagen
type XI > always found on surface of collagen fibril > determines the diameter of the fibril (high? > the fibril is very _____, if it is low? > the fibril is very _____)
type IX > contains a region that doesn’t form _____ > but is very flexible > introduces a _____ in the molecule > free to interact with other molecules, like proteoglycans
heterotypic
thin
thick
triple helix
kink
Cartilage ECM Composition • Ground Substance: – Proteoglycans: • \_\_\_\_\_ (most abundant PG). • Perlecan.
– Non-collagenous Proteins:
• Cartilage Oligomeric Matrix Protein (COMP).
• Matrilins
– Growth Factors.
Aggrecan
Cartilage Proteoglycans (PGs)
• \_\_\_\_\_ PGs: complexes with \_\_\_\_\_: – Hyaluronic acid (HA) core. – \_\_\_\_\_: • Core Protein. • \_\_\_\_\_ Sulfate • \_\_\_\_\_ Sulfate – Link Protein.
Aggregating HA aggrecan chondroitin keratin
Cartilage Proteoglycans (PG)
two types of PG in cartilage: aggregating PG’s and non-aggregating PG’s
mostly PTM by chondroiton sulfate CS and KS ???
LOOK UP NOTES
Cartilage Proteoglycans (PGs)
Cartilage Proteoglycans (PGs)
• Non-Aggregating PGs: interact with _____ fibrils:
– _____ (contains Dermatan Sulfate [DS]).
– Biglycan (DS).
– Fibromodulin (KS).
– Lumican (KS).
• Perlecan (a HS PG usually present in _____).
IX has a kink and free _____ domain can interact with PG’s
very _____, _____, high affinity for water due to the presence of high GAG
decorin basement membranes N terminal polar acidic
Cartilage Organization
cartilage is surrounded by double layer of cells known as the _____ (two sub-layers)
large proportion is due to the presence of ECM > some regions are more _____ > in close proximity to lacunae (highly stained) > _____ matrices
as you move from the lacunae, the density _____ and it is now known as the _____ matrix
difference bt the two types: territorial is richer in _____ and it doesn’t contain as many _____; interterritorial is the opposite
perichondrium
dense
territorial
drops
inter-territorial
collagen fibrils
PGs
Territorial and Interterritorial Matrices
two chondrocytes sharing the same lacuna; when two+ cells share the same lacuna, that means they are all derived from _____ (a clone of that cell, they’re now _____ cells) > group of cells is known as an _____
_____ is apparent > a lot of secretion is occuring
ancestral chondroblast
sister
isogenous group
RER
Cartilage Development and Chondrocyte Differentiation
1/2; bc the lab experiments occur during the day
condensation of _____ cell (_____) > in condensed _____ > still _____ and mesenchymal cells
the aggregation of TF > differentiation of prechondrcytes to _____; the chondrocytes/blasts are stained in blue (alcium blue)
mesenchymal
pluripotent
prechondrocyte
fibroblasts
chondrocytes
Cartilage Organization: Perichondrium
• Surrounds most cartilages. • Two layers: – Outer \_\_\_\_\_ (or fibrogenic) layer: • Spindly, fibrogenic cells, \_\_\_\_\_ between CT and cartilage. • Contains \_\_\_\_\_.
– Inner _____ layer:
• Produces _____.
fibrous
transitional
blood vessels
chondrogenic
chondroblast precursors
Cartilage Organization: Perichondrium
fibrous later is stained _____ > cells are more non-specialized fibroblasts > transitional bt reg conn tissue and cartilage > capable of _____; provide the precursors to the _____ layer
chondrogenic > mostly formed by _____; derived from the division of cells from the _____ layer; these chondroblasts are capable of further _____
two daughter cells from chondroblast > one cell stays in the _____ layer (and can divide further later); the other cell will move to the growing cartilage and _____ into chondroblast (like TAC)
pink
division
chondrogenic
chondroblasts
fibrous
division
chondrogenic
terminally differentiate
Cartilage Growth: Appositional vs. Interstitial
appositional growth: mediated by the _____; growth that takes place through the division of cells in perichondrium (chondroblasts) > providing more and more cells to the cartilage; the tissue is growing in the _____ direction
_____ days into development perichondrium is located in middle; then it migrates to where it is; grows wider and wider; more cells, more ECM; in a 3D way, all the cartilage is surrounded by perichondrium
interstitial growth: limited mitosis that takes place _____ the tissue (chondrocytes divide several times > isogenous groups: 2-4-8 cells sharing the same lacuna) > produce more matrix > provide more matrix…..?
appositional growtth in dimensional is by appositional growth
perichondrium
upward
two/three
within
Appositional Growth
Appositional growth: New layers of cells and ECM are added to the _____ of the cartilage.
- Overall size of cartilage _____.
- E.g. increase in size of embryonic cartilage template (_____) of skeleton.
- Surrounding CT.
- Perichondrium (fibrous layer):
Spindly, fibrogenic cells, transitional
between CT and cartilage. 3. Perichondrium (chondrogenic layer):
Cells differentiate into chondroblasts, which secrete and assemble Type _____ collagen.
_____ > regulates the transcription of several important genes of cartilage biology
surface
increase
anlagen
II
Sox9
Campomelic Dysplasia
• Sox9: transcription factor that controls the expression of _____ collagen and _____ genes.
• Sox9 gene mutated in campomelic* dysplasia, with _____ inheritance
• Defective _____ cells remain in the perichondrium and do not differentiate into _____.
• Phenotype: • \_\_\_\_\_ and angulation of long bones. • Hypoplasia of the pelvic and scapular bones. • Abnormalities of the \_\_\_\_\_. • Decrease in the number of \_\_\_\_\_. • Craniofacial abnormalities.
type II aggrecan autosomal dominant chondrogenic cells chondrocytes
bowing
vertebral column
ribs
Interstitial Growth
formation of _____; division of chondrocytes (1-3 times of division)
really important in the formation of bone > _____ ossification
isogenous groups
endochondral
Hyaline Cartilage
• _____.
• Surrounded by perichondrium (except in
_____ cartilage).
• Chondrocytes show _____ and
_____ matrices.
• ECM fibers of _____ collagen (invisible with
light microscopy by having the same _____ as the matrix).
• Locations: • temporary \_\_\_\_\_. • articular cartilage. • \_\_\_\_\_ (nose, larynx, trachea, and bronchi). • intercostal cartilages.
avasular articular territorial inter-territorial type II refractive index
embryonic skeleton
respiratory tract
Hyaline Cartilage: Basophilic matrix
The basophilia (redly stain) in the matrix is due to the high density of _____ charges in the GAG subunits, which attract the _____ charged dye, hematoxylin.
negative
position
Tracheal Hyaline Cartilage
rings are formed by _____ cartilage; surrounded by perichondrium in _____ directions
you can see the presence of _____ groups here
hyaline
both
isogenous
Specialized Hyaline Cartilage: Articular Cartilage
• Functions:
– Smooth surface: reduces _____.
– Resists _____ forces.
• No _____:
– Pain-free motion of joints.
– Non-perception of injury.
• No _____:
– No bruising.
– Nutrition and hydration from _____.
– No _____: repair is impaired.
No _____
_____ prevents the touching of two bones and acts as a lubricant
friction
compressive
nerves
blood vessels
synovial fluid
connective tissue
perichondrium
synovial fluid
Specialized Hyaline Cartilage: Articular Cartilage
• Structure: – Hyaline cartilage without \_\_\_\_\_. • Superficial tangential zone: collagen- \_\_\_\_\_, \_\_\_\_\_ motion. • Middle (or transitional) zone. • Deeper (or radial) PG-\_\_\_\_\_ zone: resistance to \_\_\_\_\_.
• May calcify in the _____ of the bone.
perichondrium rich frictionless rich compression vicinity
Specialized Hyaline Cartilage: Articular Cartilage
STZ: the collagen is deposited in a _____ fashion to the surface of artciulation
middle zone: most of _____ is located here; more randomly deposited but still mostly parallel organization; also less rich in collagen, not as _____
deep zone (radial): collagen fibers are deposited _____ to the tissue; very rich in _____ > most resistant to compression forces
at the connecting area bt cartilage and bone > may _____ > forming a _____ connection bt cartilage and bone
parallel
tissue
dense
perpendicular
PG
calcify
mineral
Specialized Hyaline Cartilage: Articular Cartilage
• Nutrition and Compression:
– Resting:
• PGs are hydrophilic: _____.
• PG swelling = collagen _____.
– Compression:
• Water is displaced.
• PG concentration _____.
– Relaxation:
• _____ drawn back to restore equilibrium.
• Nutrients are imported with the _____.
if something happens to synovial fluid; inflammation or destruction of syn membrane cells (pathologic cells: _____) > nutrition of cartilage will be comprimised; _____; decay and there will be direct contact of _____ contact
swelling
resistance
increases
water
water
rhematoid arthritis
starve
bone-to-bone
Elastic Cartilage • \_\_\_\_\_. • Surrounded by \_\_\_\_\_. • Chondrocytes show \_\_\_\_\_ and \_\_\_\_\_ matrices. • ECM fibers of Type \_\_\_\_\_ collagen and \_\_\_\_\_. • Functions: Resiliency and pliability. • Locations: • \_\_\_\_\_ ear • Epiglottis • \_\_\_\_\_ • Bridge of nose
avascular perichondrium territorial interterritorial II elastin external auditory tube
Fibrocartilage • \_\_\_\_\_. • Lacks a \_\_\_\_\_. • \_\_\_\_\_ and \_\_\_\_\_ aligned along stress lines.
• ECM fibers: dense bundles of Type _____ collagen.
- Functions:
- Resistance to compression and shear forces.
- Considered intermediate between _____ and _____.
- Locations:
- _____ of the intervertebral disks
- Articular disks of the knee
- _____
- Sternoclavicular joints
- _____ symphysis
the matrix that the cells deposit will be deposited along those lines make them more _____ to mechanical forces
avascular
perichondrium
chondrocytes
fibroblasts
I
hyaline cartilage
dense CT
annulus fibrosus
mandible
pubic
resistant
Fibrocartilage: The Intervertebral Disks
• Intervertebral Disks: – Nucleus Pulposus: \_\_\_\_\_. – Annulus Fibrosus: \_\_\_\_\_. • PGs induce tissue \_\_\_\_\_. • Collagen and weight resist expansion. •Long bed stays or \_\_\_\_\_ (space travel): disk expansion.
• Herniation:
– Increased swelling of the _____ with weakened _____.
– Nerve root _____ (e.g._____).
hyaline cartilage
fibrocartilage
expansion
microgravity
nucelus
annulus
entrapment
sciatica
Fibrocartilage: The Intervertebral Disks
force is perpindicular to the screen, falling along the body of the IVD
hyaline cart in NP > rich in _____ > take up water, and expand the tissue
fibrocartilage in AF > tries to balance the expansion of the hyaline cartilage by having plenty of _____
NP may go awry, may absorb too much water > swelling of the NP (hyaline cartilage) whcih induces the expansion of the AF > the organization is now off > resulting in a _____; the fibrocartilage can protude so far it can pinch a _____
only way to solve > _____; ultimately results in a contraction of the NP; allowing the AF to return to its original form (chymopapain does not damage _____)
PG
collagen
herniated disk
nerve
chemonucleolysis
collagen fibrils
Cartilage Changes with Age
• PGs in older individuals are _____ with shorter _____ chains than in younger individuals.
• Chondrocytes less efficient in renewing the ECM, thus reducing _____ content.
• Reduced _____ content in the ECM: cartilage less able to resist compressive
forces.
• Results: ECM more vulnerable to injuries in _____; inflammatory
response to injury would cause painful symptoms of _____.
smaller chondroitin sulfate PG water weight-bearing arthritis
Cartilage repair
• Very limited capacity for repair (avascular):
– Blood clot formation:
• Abrasion or drilling of _____ bone.
– Cell implantation:
• Chondrocytes/marrow stem cells.
• Artificial matrix for support.
– Tissue transplantation:
• _____ grafts.
• _____ grafts.
– Limitations:
• _____ availability – stem cells/allografts.
• _____ stability – growth factors.
• _____ integration.
subchondral
osteochondral
periosteal
cell/tissue
phenotype
chondral
Drill of subchondral bone for cartilage repair
subchondral > just below the articular cartilage (in the epiphysis) > so the bone leaves and there are _____ will repair the bone; in the cartilage area they will differentiate into _____ in the appropriate area
osteoprogenitor cells
cartilage cells
Chondrodysplasias: Genetic diseases of cartilage
_____ main groups of chrondrodysplasias; due to genetic defects in proteins that form the _____, and in proteins that regulate the _____ of the chondrocyte or the deposition of the _____
on left: mutations in types of _____
on right: FGFR3 (_____)
LOOK UP THIS TABLE AND KNOW IT
two
ECM
life
matrix
collagen
dominant negative
Chondrodysplasias: Genetic diseases of cartilage
Defects in _____ macromolecules: COL2A1
Defects in _____ macromolecules: FGFR3, SOX9
matrix
cellular
Chondrodysplasias: Genetic diseases of cartilage
COL2A1:
- Achondrogenesis type II
- _____
- Spondyloepiphyseal dysplasia
- _____
- Stickler dysplasia
- _____
FGFR3:
- _____
- _____
- Thanatophoric dysplasia type I
- Thanatophoric dysplasia type II
SOX9:
-_____
hypochondrogenesis
kniest dysplasia
familial osteoarthritis
achondroplasia
hypochondroplasia
campomelic dysplasia
