Tendon and Ageing

Question 1

How can we test the mechanical properties of tendon?

Answer 1

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)

Question 2

What might you be able to check with a load-extension graph?

Answer 2

Check how much load can be applied before failure - for the entire structure and the material

Stiffness of structure

Elastic modulus of material/tissue

Question 3

What are the different regions of a tendon load-extension graph?

Answer 3

Toe region
Elastic
Plastic
Failure

Question 4

Who is more at risk for tendon injury?

Answer 4

older people

Question 5

Define ultimate strain

Answer 5

the strain at the point of failure, where strain= x/L

Question 6

Define Ultimate force

Answer 6

Max force which can be applied to a material before permanent deformation

Question 7

Define Ultimate stress

Answer 7

the stress at the point of failure, where stress=F/A

Also more commonly called ultimate tensile strength

Question 8

Define elastic modulus

Answer 8

the ratio of the force exerted upon a substance or body to the resultant deformation. (Stress/Strain) - shows stiffness of material

Question 9

Define stiffness

Answer 9

Elastic modulus without taking cross-sectional area into account.

Question 10

What mechanical properties do not change in tendons with age?

Answer 10

Ultimate stress
Ultimate strain
Elastic modulus

In human cohorts some studies showed an increase and others decreases

Question 11

What are different possible mechanisms of ageing?

Answer 11

Genomic instablity
Telomere attrition
epigenetic alteration
Loss of proteostasis
Deregulated nutrient sensing
Mitochondrial dysfunction
cellular scenescence
Stem cell exhaustion
Altered intercellular communication

Question 12

How long do collagen an other matrix proteins “live”?

Answer 12

Long-lived

Question 13

Over time what happens to collagen and other matrix proteins?

Answer 13

They are modified and fluoresce

Question 14

Describe racemization

Answer 14

All amino acids start as their L-isomer but over time they convert into their D-isomer

Question 15

How can we use the fluorescence in older tendon to study ageing?

Answer 15

graph tendon tissue fluorescence against age

We can check the ration of amino acid racimers and work out the half-life

Question 16

What happens to tendon tissue with age?

Answer 16

Turnover decreases with age

Question 17

What happens to tendon collagen half-life with age?

Answer 17

Increases

Question 18

How do we test tendon cell activity?

Answer 18

Extract mRNA of matrix proteins/ matrix degrading proteins and use PCR

Question 19

What have tests shown us about tendon cell activity?

Answer 19

Ageing is not due to decreased matrix synthesis or the enzymes that degrade the matrix

Question 20

What happens to long-lived proteins?

Answer 20

Glycation

Question 21

What is formed due to glycation of long-lived proteins?

Answer 21

Advanced glycation end products (AGE)

These fluoresce

Question 22

What are two common AGEs?

Answer 22

Pentosidine and glucosepane

Question 23

What happens to pentosidine levels with time?

Answer 23

Increase

Question 24

What are the advantages and disadvantages of using pentosidine to study tendon glycation?

Answer 24

Disadvantages: It is in relatively low concentrations

Advantages: Fluorescent and resistant to acid hydrolysis

Question 25

What is the problem with using glucosepane to study glycation?

Answer 25

More difficult to measure (bc they are acid labile and don’t fluoresce)

Question 26

Glucosepane may have more of an impact on ageing tendon than pentosidine

TRUE or FALSE

Answer 26

TRUE

forms crosslinkes just like pentosidine

Question 27

How do AGEs form?

Answer 27

Collagen + glucose –> fructose lysine –> collagen is bound to arginine

–> glucosepane
or
–> oxidation + ribose –> pentosidine

Question 28

What effect might glycation have on the tendon?

Answer 28

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

Question 29

What does 1CTP stand for?

Answer 29

Cross-linked carboxyterminal telopeptide of type I collagen

Question 30

What does 1CTP give an indication of?

Answer 30

How much collagen is broken down

Question 31

What happens to 1CTP with age?

Answer 31

It decreases

Question 32

What is a risk factor for tendon injury?

Answer 32

exercise (athletes and recreational)

Question 33

How can we measure the effect of exercise on tendons?

Answer 33

Check:

Tendon size (hypertrophy)
Change in material property (structure /composition)
Change in ways cells function

Question 34

What is the effect of exercise on tendon hypertrophy?

Answer 34

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

Question 35

What is the effect of exercise on tendon composition and organisation?

Answer 35

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

Question 36

What effect does exercise have on cell metabolism?

Answer 36

Blood flow: Acute exercise increases blood flow

Collagen turnover: Increases after acute exercise

Collagen synthesis: Increases after exercise