Tendon and Ageing Flashcards
How can we test the mechanical properties of tendon?
In vitro: eg. with hydrolic materials testing machine (clamps pull the tendon, can measure the force applied and the displacement of clamps to make a load-extension graph)
What might you be able to check with a load-extension graph?
Check how much load can be applied before failure - for the entire structure and the material
Stiffness of structure
Elastic modulus of material/tissue
What are the different regions of a tendon load-extension graph?
Toe region
Elastic
Plastic
Failure
Who is more at risk for tendon injury?
older people
Define ultimate strain
the strain at the point of failure, where strain= x/L
Define Ultimate force
Max force which can be applied to a material before permanent deformation
Define Ultimate stress
the stress at the point of failure, where stress=F/A
Also more commonly called ultimate tensile strength
Define elastic modulus
the ratio of the force exerted upon a substance or body to the resultant deformation. (Stress/Strain) - shows stiffness of material
Define stiffness
Elastic modulus without taking cross-sectional area into account.
What mechanical properties do not change in tendons with age?
Ultimate stress
Ultimate strain
Elastic modulus
In human cohorts some studies showed an increase and others decreases
What are different possible mechanisms of ageing?
Genomic instablity Telomere attrition epigenetic alteration Loss of proteostasis Deregulated nutrient sensing Mitochondrial dysfunction cellular scenescence Stem cell exhaustion Altered intercellular communication
How long do collagen an other matrix proteins “live”?
Long-lived
Over time what happens to collagen and other matrix proteins?
They are modified and fluoresce
Describe racemization
All amino acids start as their L-isomer but over time they convert into their D-isomer
How can we use the fluorescence in older tendon to study ageing?
graph tendon tissue fluorescence against age
We can check the ration of amino acid racimers and work out the half-life
What happens to tendon tissue with age?
Turnover decreases with age
What happens to tendon collagen half-life with age?
Increases
How do we test tendon cell activity?
Extract mRNA of matrix proteins/ matrix degrading proteins and use PCR
What have tests shown us about tendon cell activity?
Ageing is not due to decreased matrix synthesis or the enzymes that degrade the matrix
What happens to long-lived proteins?
Glycation
What is formed due to glycation of long-lived proteins?
Advanced glycation end products (AGE)
These fluoresce
What are two common AGEs?
Pentosidine and glucosepane
What happens to pentosidine levels with time?
Increase
What are the advantages and disadvantages of using pentosidine to study tendon glycation?
Disadvantages: It is in relatively low concentrations
Advantages: Fluorescent and resistant to acid hydrolysis
What is the problem with using glucosepane to study glycation?
More difficult to measure (bc they are acid labile and don’t fluoresce)
Glucosepane may have more of an impact on ageing tendon than pentosidine
TRUE or FALSE
TRUE
forms crosslinkes just like pentosidine
How do AGEs form?
Collagen + glucose –> fructose lysine –> collagen is bound to arginine
–> glucosepane
or
–> oxidation + ribose –> pentosidine
What effect might glycation have on the tendon?
May affect the ability of enzymes to degrade collagen
May also impact mechanical properties at collagen molecule and fibril level, interaction of collagen with other matrix proteins and cells
What does 1CTP stand for?
Cross-linked carboxyterminal telopeptide of type I collagen
What does 1CTP give an indication of?
How much collagen is broken down
What happens to 1CTP with age?
It decreases
What is a risk factor for tendon injury?
exercise (athletes and recreational)
How can we measure the effect of exercise on tendons?
Check:
Tendon size (hypertrophy) Change in material property (structure /composition) Change in ways cells function
What is the effect of exercise on tendon hypertrophy?
In athletes Achilies tendons were bigger than non-athletes but training didn’t seem to change their size
Older horses didn’t get larger tendons from exercise but younger ones did
Conclusion: Different tendon types may respond differently and there may be a window of opportunity during maturation
What is the effect of exercise on tendon composition and organisation?
Water content sometimes decreases (depending on tendon type)
Cellularity doesn’t change
Collagen content stays the same but fibril diameter decreases
Exercise decreases GAG levels
What effect does exercise have on cell metabolism?
Blood flow: Acute exercise increases blood flow
Collagen turnover: Increases after acute exercise
Collagen synthesis: Increases after exercise
