Cartilage Flashcards
(23 cards)
Osteoarthritis (OA) is a joint disease with effects on both cartilage and bone. Mechanical wear, the cell response and inflammation play a role in the progression of the disease.
What are two main early pathological tissue changes observable in CARTILAGE? What changes to the tissue cause each to occur? How does each change contribute to the progression of OA?
- Softening: Loss of GAG and to a lesser extent damage to the collagen network. Loading will create higher magnitude strains in the tissue causing further damage to PG and collagen network and/or collagen network restructuring.
- Fibrillation and fissures: Damage to the collagen network either in the STZ. Complete destructuring of the MZ/DZ. Breakage of collagen fibrillar cross-links. Structural damage to collagen network allows for loss of GAGs, which then softens the tissue (see above).
STZ= superficial tangential zone
Osteoarthritis (OA) is a joint disease with effects on both cartilage and bone. Mechanical wear, the cell response and inflammation play a role in the progression of the disease.
What are two main pathological tissue changes that can be found in BONE? What changes to the tissue cause each to occur? How does each change contribute to the progression of OA?
- Sclerosis: Thickening of the subchondral bone plate or increased density of the subchondral bone. This results in stiffer subchondral bone underlying the cartilage, increasing the peak transient reactive stresses/strains in cartilage under fast loading which may cause damage to cartilage.
- Advancing tidemark: Further advancement of endochondral ossification in the DZ. This causes thinning of cartilage, which increases the strain under similar deformations.
- Osteophytes (=bone spurs): Response of bone to increase the joint surface area stimulated by increased stresses/strains in subchondral bone. At the extreme ROM, these can cause impingements (‘inklemming’) causing further damage or joint destabilization.
Corticosteroids inhibit inflammation but also inhibit processes associated with wound healing. They are sometimes administered (injection) in OA joints. Whether this is beneficial depends on the cause of OA. Do you think corticosteroid injection would be useful to treat OA that originates from mechanical overloading? Explain your answer in a few lines.
Yes, it could be because tissue damage elicits an inflammatory response which can cause further degradation of the tissue and corticosteroids would reduce this.
No, early in the disease, attempts to repair the damage cause by mechanical overloading would be blocked by corticosteroids.
Important would be to see first if a chronic inflammatory process is present, e.g. joint effusion, redness, warmth, etc.
There are several surgical techniques to treat focal cartilage lesions in the knee. The most frequently used one is micro-fracturing. Mention 3 other techniques (excluding microfracturing and corticosteroid injections) and provide for each of them an advantage and a disadvantage, compared to micro-fracturing.
OATS: immediate load bearing/rapid recovery, donor site morbidity.
ACI: hyaline cartilage regeneration, two operations.
Synthetic implants: cheap, possible damage to opposing cartilage.
In an experiment, an osteochondral explant is placed in an unconfined compression setup, i.e. between two rigid impermeable flat parallel plattens with surface area much greater than the cross section of the osteochondral cylinder, all bathed in an aqueous bath. During this experiment, several biochemical and mechanical conditions are applied to the construct.
Q1: Under one of these conditions, the size of the cartilage increases slowly in all directions (x, y and z), until an equilibrium was reached. Which condition was changed, and how was it changed (i.e. higher/lower etc.), compared to the condition that prevailed before?
A1: External bath had lower osmotic pressure, i.e. lower saline concentration.
In an experiment, an osteochondral explant is placed in an unconfined compression setup, i.e. between two rigid impermeable flat parallel plattens with surface area much greater than the cross section of the osteochondral cylinder, all bathed in an aqueous bath. During this experiment, several biochemical and mechanical conditions are applied to the construct.
Under another condition, the size instantly decreases in z-direction but increases in x- and y–direction, as measured halfway between the bone and the surface of the cartilage. After this condition was applied, the size of the sample in z-direction was not allowed to change anymore.
Q1: Which condition was changed, compared to the condition that prevailed before?
Q2: What is the name of such experiment/test-condition?
Q3: Describe the shape of the cartilage at the external radial surface going from the bone cartilage interface to the articular surface under this condition (or make a clear drawing). Please explain what tissue morphology/mechanism is responsible for this shape.
A1: A step unconfined compression was applied to the cartilage surface, i.e. mechanical compression.
A2: Relaxation test.
A3:
- Superficial layer: medium radial expansion –> Due to the orientation of the fibers in the superficial zone, the sideways expansion of the surface is limited more than in the intermediate/middle zone.
- Middle zone: largest radial expansion.
- Attachment to bone/ deep zone: no radial expansion –> In the deep zone, cartilage is attached to bone and cannot expand.
In an experiment, an osteochondral explant is placed in an unconfined compression setup, i.e. between two rigid impermeable flat parallel plattens with surface area much greater than the cross section of the osteochondral cylinder, all bathed in an aqueous bath. During this experiment, several biochemical and mechanical conditions are applied to the construct.
Interestingly, immediately after this condition was applied, it was measured that the increase in x-direction was larger than the increase in y-direction.
Q1: What may have caused such difference?
Q2: What additional experimental technique could you use to prove that your suspicion (above answer) is correct?
A1: Collagen fiber orientation in the superficial plane was oriented and not random, i.e. split-lines.
A2: Split line patterns or histology with polarized light and compare histology in different directions, or observe fiber orientation with SEM.
In an experiment, an osteochondral explant is placed in an unconfined compression setup, i.e. between two rigid impermeable flat parallel plattens with surface area much greater than the cross section of the osteochondral cylinder, all bathed in an aqueous bath. During this experiment, several biochemical and mechanical conditions are applied to the construct.
Under another condition, the size instantly decreases in z-direction but increases in x- and y–direction, as measured halfway between the bone and the surface of the cartilage. After this condition was applied, the size of the sample in z-direction was not allowed to change anymore.
After this condition was maintained for a full hour, what do you think happened to the following measures, compared to the moment that the condition was just applied? Explain your answer.
Q1: The size of the cartilage in x- and y-direction.
Q2: The osmotic pressure in the cartilage.
Q3: The stress in the solid matrix of the cartilage.
A1: Decreases: fluid flows out and total sample size decreases while z-size does not change.
A2: Increases: water flows out increasing FCD and therefore osmotic pressure.
Q3: Increase: Immediately after compression, there is a fluid pressure that drives fluid out of the cartilage. Thus, load is carried by fluid pressure, swelling pressure and solid stress. At equilibrium, there is no-longer fluid flow and fluid pressure is zero. Thus, the external load is carried by swelling pressure and stress in the deformed solid. The division of this is unknown, but because there is less of a Poisson’s effect in the x and y directions, stress in the z direction will be higher.
In an experiment, an osteochondral explant is placed in an unconfined compression setup, i.e. between two rigid impermeable flat parallel plattens with surface area much greater than the cross section of the osteochondral cylinder, all bathed in an aqueous bath. During this experiment, several biochemical and mechanical conditions are applied to the construct.
The exact experiment was repeated with another sample. All applied conditions resulted in qualitatively similar changes in the shape of the cartilage. However, for the first sample, all changes reached equilibrium in one hour but for the second sample, equilibrium was reached only after 2 hours.
Q1: Which mechanical parameter is responsible for this difference?
Q2: If the second sample was 2x thicker than the first sample, how is it quantitatively different to the first sample? Explain your answer mathematically.
A1: Permeability, k.
A2:
2t1 = t2. As t = h2/kHa, 2h12/k1Ha = h22/k2Ha. If h2 = 2h1, then 2h12/k1 = 4h12/k2 or 1/k1 = 2/k2 or k2 = 2k1.
- load support in AC & IVD?
A. Elasticity/viscosity/porosity
B. Swelling/restriction/distribution
C. Solid deformation/fluid flow/entropy
B
gel made of proteoglycans has swelling
potential when placed in a normal saline bath.
This swelling potential is called its osmotic
pressure. When fully swollen what is its osmotic
pressure?
A. 0
B. low
C. high
A + B
When a gel made of proteoglycans is
restricted from swelling, it has a nonzero
osmotic pressure. What is this balanced by?
A. The tensile forces in the restricting element.
B. The hydraulic pressure in the fluid.
C. Both.
C
Muscle contraction is necessary for joint formation in the embryo. By what mechanism is this stress/strain transduced into the separation necessary for joint formation?
A. Direct pulling apart of cells which have lost cell attachments.
B. Cell migration away from high strain locations.
C. Apoptosis of cells via high strain.
D. Stimulating the production of hyaluronic acid.
C?
Apoptosis of few cells in cavity àconnection between cells is lost
HA synthesis in cavitation àswelling àcells separate if not connected
HA synthesis enhanced by strain
Increase in tissue volume in the physesis due to? A. Cell proliferation. B. Cell hypertrophy. C. Matrix production. D. Swelling.
What else is necessary?
B
Matrix degradation
What is the major PG in AC & IVD(NP)? A. perlecan. B. decorin. C. biglycan. D. aggrecan.
D
What is the main sGAGin aggrecan? A. dermatinsulfate. B. chondroitin sulfate. C. keratan sulfate. D. hyaluronic acid.
B
What are the main collagens in AC? A. Type I. B. Type II. C. Type VI. D. Type IX. E. Type XI.
- Type II (2) –> 85-90% of collagen in AC
- Type IX(9) –> outside type II, XI (11) –> inside type II. Restrict lateral growth of collagen II. Attachment between collagen & PG or cells.
- Type VI (6) –> form their own network in the environment of the chondrocytes.
- Type I –> the most #collagen in other tissues
There is a strong bond between calcified cartilage and the underlying subchondral bone. What is the main element for this strength? A. Collagen-II B. Collagen-I C. Mechanical interlocking D. hydroxy-appatitecrystals
A
When articular cartilage is compressed, the way the collagen fibers bend is dependent on the magnitude of compression. How do they bend under small compressive loads?
A. Many small buckling crimps creating a wavy
pattern.
B. One large buckling crimp.
A
If after equilibrium is reached, a further compression is applied. Is the relaxation of reactive force:
A. faster
B. slower
C. same
B and C both possible.
More compressive strain –>smaller pores –> less permeable (lower k).
Relaxation is influenced by:
1. Permeability (influenced by strain)
2. stiffness ( not so much influenced by strain)
A computer model of cartilage is developed where it’s described as: biphasic, reinforced with viscoelastic non-linear fibers exhibiting swelling properties through Donan osmosis.
The model does not include strain-dependent permeability, thermal expansion, & water partitioning into fibers and cells.
Name 2 parameters of this model that determine the time-dependent behavior of the tissue. A. Swelling B. Poroelasticity C. Aggregate modulus D. Fiber viscoelasticity E. B & D
E
Swelling and aggregate modulus describe equilibrium characteristics. Characteristics that describe time-dependent parameters are usually related to phenomena with energy/work loss, e.g. viscous fluid flowing through pores and molecules and fibers sliding past each other.
You compare the model simulations to experimental data and observe that the model response is correct for small compressive strains but it’s too quick for experiments under larger strains.
What do you need to add to the model and why? A. Thermal expansion B. Viscoelastic ground substance C. Strain dependent permeability D. Intrafibillar water E. None of the above
C
Larger strains decrease pore size –> creating more resistance to fluid flow –> lower permeability.
