11/13: Chondrocytes & Cartilage Flashcards
- What is cartilage?
a. Specialized connective tissue
- What makes cartilage regeneration limited?
a. Its avascular nature
- What are the three types of cartilage?
- Hyaline cartilage
- Elastic cartilage
- Fibrocartilage
- What collagen types make up hyaline cartilage?
a. 2 and 10
- Is hyaline cartilage the most abundant type of cartilage found in the body?
a. Yes
- Where is hyaline cartilage found?
a. Growth plates
b. Skeleton precursor
c. Joint articular surfaces
d. Costal cartilages
e. Nose, ears, trachea, larynx
What collagen type is found in elastic cartilage?
a. Type 2 collagen
- Where is elastic cartilage found?
a. Pharyngotympanic tubes
b. Epiglottis
c. Ear lobes
- What collagen type makes up fibrocartilage?
a. Type 1 collagen and hyaline cartilage type 2
- Where is fibrocartilage found at?
(PIT)
a. Pubic symphysis
b. IV discs
c. TMJ
- What do all osteoblasts, chondrocytes, myoblasts, and adipocytes start as before they differentiate?
a. Mesenchymal progenitor
What are the different zones of bone growth?
Mnemonic: Real, People, May, Have, Career, Options
a. Zone of reserve cartilage
b. Zone of proliferation
c. Zone of maturation
d. Zone of hypertrophy
e. Zone of degeneration/calcification
f. Zone of ossification
What is the principal engine for longitudinal bone growth?
a. Proliferation of columnar chondrocytes and expansion of chondrocyte size
What is the main master transcription factor in chondrocyte differentiation?
SOX9
What does SOX9 do to mesenchymal cells?
a. Turns them into chondrocytes and flat columnar chondrocytes
What turns flat columnar chondrocytes into terminal hypertrophic chondrocytes?
a. RUNX2
b. OSX
- Does SOX9 drive differentiation down the chondrocyte pathway?
Yes
- What cells express SOX9?
a. Chondroprogenitors and proliferating chondrocytes
In order for prehypertrophic and hypertrophic chondrocytes to proliferate, what must be down regulated?
SOX9
Does SOX9 inhibit RUNX2?
Yes
If Runx2 is deleted, what happens to chondrocyte?
They fail to mature
What collagen type do hypertrophic chondrocytes express?
Type 10
What do the chondrocytes express in order to allow for mineralization?
Alkaline phosphatases
What do the chondrocytes express in order to allow for vascular invasion to occur?
MMP13 and VEGF
What are the two ligands chondrocytes bind to?
PTHrP
lHH
What are the receptors for PTHrP and IHH?
PTC1 and PTH1R
What do the ligands and their receptor binding regulate?
Chondrocyte proliferation/differentiation
Do the ligands and their receptors also determine when chondrocytes enter
hypertrophy?
Yes
What are the 6 steps used by IH/PTHrP in regulating chondrocyte differentiation?
- PTHrP produced early by chondrocytes near growth plate
- PTHrP activates when it binds to PTH1R later in growth stopping chondrocytes from proliferation
- Chondrocytes stopped become prehypertrophic and produce IHH
- IHH causes chondrocytes to proliferate
- IHH acts upon adjacent cells causing them to produce more PTHrP
- Mineralized bone collar forms
What does this loop ensure?
It ensures that there is always a constant supply of chondrocytes replacing dead chondrocytes
- Which fibroblast growth factors is important in chondrocyte growth?
FGF
- What is FGFR3 used as?
A regulatory step in the PTHrP and IHH cycle to ensure chondrocytes do not over proliferate
- Does FGFR3 inhibit IHH?
Yes
- What are the 3 key ECM proteins expressed in cartilage?
a. Type II collagen
b. Aggrecan
c. Type X collagen
- Is type II collagen a heterotrimer or homotrimer?
Homo
- What gene codes for type II collagen?
COL2A1
- What cartilage type expressed type X collagen?
Hypertrophic cartilage
- Is type X collagen a homotrimer or heterotrimer?
Homo
What genes code for type X collagen?
COL10A1
What is the first sugar residue in a GAG?
Amino sugar
i. Either usually N-acetylglucosamine or N-acetylgalactosamine
What is the second sugar residue in a GAG?
Uronic acid
What are the 4 main GAG types in cartilage?
- Hyaloruan
- Chondroitin sulfate/Dermatan sulfate
- Heparan sulfate/Heparin
- Keratan sulfate
What are most GAGs found covalently attached to?
Proteoglycans
What are the two major proteoglycans?
Aggrecan
Versican
What GAG types are found attached to aggrecan?
a. Keratan sulfate
b. Chondroitin sulfate
- What does aggrecan assemble with to form huge chains?
a. Hyaluronan
- What disease results from mutations that affect cartilage differentiation and function?
a. Chondrodysplasisa
- What does Chondrodysplasia cause?
a. Skeletal growth defects and deformities
- What is camplomelic dysplasia?
a. A disease caused by a loss of function mutation in SOX9
- Is Camplomelic Dysplasia life-threatening neonatally?
Yes
- What can happen if PTHrP signaling is affected?
a. Prehypertrophic chondrocytes will enter hypertrophy too early and cause premature growth plate maturation
- What can happen if IHH signaling is impaired?
a. Proliferating cells will not be replaced once they become hypertrophic
- What do both scenarios lead to?
a. Growth retardation
- What can GOF mutations in FGFR3 cause?
a. Achondroplasia
- What does achondroplasia cause?
a. Short stature
b. Short bones
- What are the 3 types of mutations linked to collagen type II and chondrodysplasia
a. Lethal
b. Severe
c. Mild
- What are the mild type II collagen chondroplasyia diseases?
a. Stickler syndrome
- What are the severe type II collagen chondroplasyia diseases?
a. Spondyloepiphyseal dysplasia
- What are the lethal type II collagen chondroplasyia diseases?
a. Achondrogenesis type II
- What do all mutations that lead to achondrogenesis type II have in common?
a. They are all caused by the replacement of glycine to a bulkier amino acid in the triple helical region
- What diseases are caused by COL10A1 gene mutations?
a. Schmid-Type Metaphyseal chondrodysplasia
- Is spondyloepimetaphyseal dysplasia an autosomal recessive disease?
Yes
- What causes spondyloepimetaphyseal dysplasia?
a. A mutation in aggrecan
