201 L5 Flashcards
Tissues under load
Tissues designed to cope with mechanical forces are specialised ——— tissue.
Connective
What are some tissues that have specialised connective tissue to cope with mechanical forces?
Tendons
Ligaments
Cartilage
Bone
What is the feature of tissues that makes them different from each other?
Composition of the ECM
What are the predominant components of the ECM that determines the tissues mechanical properties?
Collagen Proteoglycans Glycoproteins Hydroxyapitite (for bone) Water
Connective tissue will ——— if the mechanical environment changes.
Remodel
What are the components of connective tissue?
Cells
ECM
What are the main cells of the connective tissue?
Chondrocytes
Fibroblasts
Bone cells
What is the function of the cells in the connective tissue?
Maintain and produce the ECM
What is the function of the ECM collagen fibres?
Resist tension (pulling of fibres)
What is the function of the ECM proteoglycans?
Resist compression
What component of the ECM is incompressible?
Water
Name the types of collagen, their function, location and what cells produce them?
Type 1 - Most abundant, bundled, found in skin, bone, ligaments/tendons produced by fibroblasts and osteoblasts.
Type 2 - cartilage, fibres, produced by chondrocytes
Type 3 - reticular fibres, found in skin, blood vessels, new bone
Type 4 - Basal lamina, form a porous mesh layer in the epthelieum.
Collagen type 1 formation:
- Synthesis of — —- — containing __-__-__ repeats.
Production of —— chains in the —— ——- ——.
The typical type 1 fibre has a ——– and two other —- —-, then it repeats.
Common — —– are —— and —–.
There is the addition of ——- groups when it goes to the golgi. This helps to tightly —– the —–. - self ——— of —– __-__ chains.
- ————- triple helix formation followed by secretion into the ——-.
- Cleavage of ———-.
The ———- stop the ———- molecule from self ——- with other pro —— molecules. Therefore preventing ——— of the cell. - self assembly into ——–
- Aggregation of —– —- to form a —– —–.
- Synthesis of pro alpha chain containing Gly-X-Y repeats.
Production of alpha chains in the rough endoplasmic reticulum.
The typical type 1 fibre has a glycine and two other amino acids, then it repeats.
Common amino acids are proline and lysine.
There is the addition of hydroxy groups when it goes to the golgi. This helps to tightly bind the coil. - Self assembly of 3 pro-alpha chains.
- Procollagen triple helix formation followed by secretion into the ECM.
- Cleavage of propeptides.
The propeptides stop the procollagen molecule from self assembly with other pro-collagen molecules. Therefore preventing apoptosis of the cell. - self assembly into fibrils
- Aggregation of collagen fibrils to form a collagen fibre.
What contributes to the mechanical strength at the molecular level?
Small glycine in the middle of helix - tight coiling
Hydroxylation - bonding of the helix
Covalent bonding at the fibril level
What are two disease associated with collagen production?
Scruvy - vitamin C deficiency = no collagen coiled structure formed
Osteogenesis imperfecta - Mutations in two genes that encode for collagen type 1.
What is a proteoglycan?
A core protein + 1 or more covalently attached GAG chains.
Features of GAGs
Long, linear ——- ———-
——— charged due to the occurence of ——- and —- – groups (attract water)
Chains consist of repeating ——– units.
Big —– components of tissue - resistance of — and ——.
Number and type of GAG chains determines ——— of the ——–.
Long, linear carbohydrate polymers.
Negatively charged due to the occurence of sulphate and uronic acid groups (attract water)
Chains consist of repeating dissacharide units.
Big water components of tissue - resistance of load and compression.
Number and type of GAG chains determines properties of the proteoglycan.
What are three proteoglycans that have multiple GAG chains?
Agreccan
versican
perlecan
What proteoglycal has 1 GAG chain?
Decorin
Hyaluronic acid is the only GAG that is —- ——–.
It is ——– expressed in the body and has several different —— depending on how many HA molecules bind together.
Hyaluronic acid is the only GAG that is not sulphated.
It is ubquitously expressed in the body and has several different functions depending on how many HA molecules bind together.
Why is hyaluronan important for tissue?
It binds large amounts of water and is therefore important for tissue hydration, joint lubrication
and diffusion of molecules.
In cartilage name the predominant proteoglycan, GAGs, relative abundance and its function.
Agrecan
Chondroitin sulphate and keratin sulphate
High
Compression
In bone name the predominant proteoglycan, relative abundance and its function.
Decorin
Low
Controls the diameter of the collagen fibre - allows more or less fibrils
In the tendon name the predominant proteoglycan, relative abundance and its function.
Decorin
Very Low
Controls the diameter of the collagen fibre - allows more or less fibrils
In intervertebral discs name the predominant proteoglycan, GAGs, relative abundance and its function.
Agrecan
Chondroitin sulphate and keratin sulphate
High in the centre (nucleus pulposas)
Low in the annulus fibrosus (outer layer of collagen)
Compression
What happens in mucopolysaccharidosis?
What are the effects?
Name 2 diseases?
The accumulation of proteoglycans in the cell due to inactivity of lysosomal enzymes
Some of the proteoglycans can fragment and drive the disease making it more
inflammatory.
Hurler’s syndrome
Hunter’s syndrome
What happens to agrecan if there are problems with link proteins of hyaluronan?
The structure weakens
Name 3 other molecules and their functions that are in the ECM?
Link proteins - join proteoglycans to hyaluronic acid in cartilage.
Fibronectin - connects cells to collagen through integrins.
Elastin - resilience
Elastin is a molecule that —- up to form the ——- —— via —— bonding.
Elastin is a molecule that builds up to form the elastic fibres via covalent bonding.
