Collagen Biochem and Matrix Disease Flashcards
how much of the ECM makes up our body composition?
80%
what is the ECM?
cellular component of tissues
what does the ECM do?
-provides a scaffold for tissue development
-provides mechanical basis for cell attachment and movement
-transmits force
-withstand compression in cartilage and IVD
-provides survival signals to cells
-reservoir for growth factors
what makes up the ECM?
-water (50%)
-proteins
-glycoproteins
-proteoglycans
-GAG’s
what is the structure of collagen?
-30% of protein mass
-major component of connective tissue
-Gly-X-Y repeat
-triple helical structure
-tesnile forces
what do most common collagen disease mutate?
glycine
what is the function of facit collagen?
regulate fibril diameter, modify fibril interactions
what is the function of network forming collagen?
molecular sieves, planar support for cells
what is the function of transmembrane collagen?
cell matrix interactions, planar support for cells
what is the function of endostatin producing collagen?
produce regulators of cell migration and signalling
what is the function of anchoring fibril collagen?
cell matrix interactions
what is the function of bead forming collagen?
elasticity, long range connectivity
what is the structure of a collagen triple helix?
-3 poly peptide chains
-each chain Is a polypro line helix
-three chains fold into a triple helix
-each chain has a repeating glycine-X-Y residue triplet
what is the process of the collagen maturation?
-pro alpha chains come together in the ER
-proline residues get modified becoming hydroxylated
-this helps protein fold
-lysines are also hydroxylated, becoming a substrate for sugar molecules to attach to
-once triple helix is formed, amino acid no longer available and get secreted
what enzymes cleave the end C/N pro peptides?
C-proteinase
Bmp1 (tolloid family)
N-proteinase
ADAMTS family members
(a disinterring and metalloproteinase with thrombospondin repeats)
what is the half life of collagen?
120 years
where is there collagen turnover?
some turnover on the peripheral edges of tendons ect but in the central core there is none
how does type I OI present?
-less severe
-asymptomatic at birth
-early onset, few fractures
-null mutations, mutations that prevent or stop collagen being produced, not enough to make fibrils
-reduced collagen levels, no issues with quality
what kind of mutations can cause mild OI?
stop codons - lead to premature stop codon, don’t have enough protein produced
promoter mutations - affecting amount of collagen being produced
mRNA instability - so it is degraded and not translated
what is recessive OI?
-enzyme mutation stops collagen secretion
-prevents aggregation of collagen inside
what are some more severe mutations that are present with OI?
-triple helix formation is stopped, continues becoming more modified which affects protein binding
-reduced quality
-therefor not only you have a mutant collagen, less collagen also
what is FACIT collagen?
a type of collagen and also a proteoglycan that have two or more triple-helical domains that connect to collagen fibrils and share protein domains with non-collagen matrix molecules
what is the structure of pro-collagen?
still unwound at the ends, ends need to be modified
which amino acids mainly make up collagen?
-glycine found at almost every 3rd residue
-proline makes up about 17% of collagen
what is the main type of collagen present in articular cartilage?
type 2
what is the main type of collagen present in a normal tendon?
type 1
what kind of cells are in a tendon?
tenoblasts
tenocytes
chondrocytes
synovial cells
vascular cells
what are tenoblasts?
immature tendon cells, initially they are different in size and shape but as they age they become elongated and spindle shapes to form into tenocytes
what are tenocytes?
mature tendoblasts, responsible for turnover and maintenance of the ECM. respond to mechanical load of the tendon and make adaptations.
how are tenocytes arranged?
arranged in longitudinal rows and have extensive communication with adjacent cells usually via gap junctions
what connects tendons to bone?
sharpey fibres
