L11 Flashcards
what is cartilage
a specialized connective tissue
what are the types of cartilage
hyaline: ribs, nose, larynx, trachea, articular joints
fibro: joint capsules, ligaments
elastic: ear, epiglottis, larynx
what is the only type of cells found in cartilage
chondrocytes
what are the two key components found in articular cartilage
Collagen (type II) and aggrecan
what are Collagen (type II) and aggrecan important for
strength and support
what happens in Ehlers Danlos syndrome
defective deposition of collagen causing
hyperextensible joints
PG are highly charged therefore attract water and form a hydrated gel. what does this do
provides resistance to compression
results in swelling pressure (turgor)
provides strength and support
what are the features of chondrocyte
only 5-10% of ECM volume
large and mature,
in groups of 2-8 cells
rich in RER and Golgi
secrete high amounts of type II collagen and aggrecan
in which ECM are chondrocytes found
avascular (hypoxic)
alymphatic
aneuronal
when do Chondrocytes differentiate
during embryonic development
what cells do Chondrocytes differentiate from
mesenchymal stem cells MSC
cells that make cartilage can change their matrix to make bones
TRUE
what are the features of MSC that differentiate into chondrocytes
expression of Sox-9 (HMG-box DNA binding
transcription factor) leads to Col2A expression
chondrocyte proliferation and ECM synthesis
requires:
- TGF-b, fibroblast growth factor (FGF),
- insulin-like growth factor (IGF-1)
- parathyroid hormone-related protein
(PTHrP)
As a result of “spatial” chondrocyte proliferation and ECM synthesis, the “cartilage model” forms during embryonic development
what is ossification
bone formation
what is Intramembranous/Endochondrial Ossification
“cartilage model” is replaced by bone during fetal development. e.g. long bones
what initiates Endochondrial Ossification
differentiation of MSC into osteoblasts, chondrocytes die and cavities (lacunae) form
what cells are present in bones
osteoblasts
what are morphogens
secreted signaling molecules that orchestrate Spatial patterning (location) of chondrocytes
during bone formation
how does Spatial patterning (location) of chondrocytes happen during bone formation
via inductive signaling
what does inductive signaling mean
cells away from other cells become different in a spatial way
what does inductive signaling require
morphogens passing between cells through the developing ECM
what members of the Hedgehog family of proteins are involved in inductive signaling
Sonic (SHH), Desert (DHH), Indian IHH)
what does inducive signaling control
the production of the key skeletal morphogen PTHrP.
how do IHH and PTHrP interact
positive feedback loops that maintain spatial chondrocyte proliferation
what does hedgehog interact with in drosophila, and what does this result in
with Patched and Smoothened,
keeps proteolytic processing of Cubitus interruptus (Ci) turned off, so it can move to nucleus and activate gene expression
what is Ci in vertebrates
GL11-13
what does hedgehog do
activates smoothened
repressor is cleaved
leading to transcription of hedgehog target genes
what happens when PTHrP binds to a G-protein coupled receptor (GPCR)
+ve feedback
what does osteoid ECM contain
hydroxyapatite and collagen
what happens to osteoid ECM when cartilage is catabolized
it becomes calcified, trapping osteoblasts
How does the morphogen IHH induce hyaline cartilage polarization within the long bones
it regulates Chondrocyte Proliferation and Hypertrophy
IHH induces the expression of PTHrP in the resting zone.
PTHrP acts on proliferative and prehypertrophic chondrocytes to delay their hypertrophic differentiation.
This creates a negative feedback loop:
- IHH promotes PTHrP production.
- PTHrP inhibits hypertrophic differentiation, maintaining a balance between proliferation and maturation.
This feedback ensures the proper spatial arrangement and polarization of chondrocytes within the growth plate.
