Collagen And Connective Tissue Flashcards
What are connective tissues?
Highly specialised tissues that provide mechanical support and assist in movement.
matrix around cells regulated their behaviour.
May contain blood vessels, nerves.
Arena for fighting infections.
Diverse structure and function but composed of the same building blocks.
Connective tissue - cartilage, bone, tendon, skin.
What are the components of connective tissue?
Cell - dynamically synthesise and break down the connective tissue - fibroblasts in skin, tendon an ligament, chondrocytes in cartilage, osteocytes, osteoblasts, osteoclasts in bone.
Extracellular matrix - structural components - ‘ground substance (mostly proteoglycans e.g aggrecan), elastic fibres, collagen fibres. Matricellular proteins - have regulatory, non-structural roles.
What are proteoglycans?
Important for mechanical properties of connective tissues.
Consist of protein core, decorated with sugar (called ‘glycans’ or ‘glycosamnioglycans’ or ‘GAGs’).
E.g aggrecan
Variable in size
Hold water in tissues, confer viscoelastic properties, interact with cells, cytokines and collagen.
What is aggrecan?
Forms huge multimeric aggregates in cartilage.
Link protein stabilises binding to hyaluronan (HA) ‘backbone’.
Huge complexes of sulfated chondoitin and keratin sulfate are highly hydrophilic - draws water into tissue and so enables cartilage to resist compression.
What is biochemistry of osteoarthritis?
Degradation of aggrecan and type II collagen impairs mechanical properties of cartilage.
In OA altered joint mechanics causes breakdown of aggrecan (sown here by red stain) and also collagen by proteolytic enzymes.
This impairs cartilage functions, causing pain in affected joints.
What are elastic fibres?
10 no microfibrils.
Consist of multiple components: elastin, fibrillin -1, -2, -3, fibulins (esp 4 and 5), matrix-associated glycoproteins.
Structural role - enable stretching of blood vessel walls, alveoli, bladder, tendons.
Regulatory role - regulate targeting and activation of growth factors (esp TGFb)
What is collagen?
There are 27 collagens made from 42 genes. Many roles and functions
Key one is fibril-for in collagens types I, II, III, V, XI, XXIV, XXVII. Have a triple helix structure = strength and stability.
Also fibril associated collagens types IX, XII, XIV, XIX, XX, XXI, XXII, XXVI.
What are collagen fibrils (type I, II, III)
Main structural component of connective tissues.
Very plentiful protein - around 15% of whole body protein content.
Collagen fibrils are made of many collagen molecules, with each molecule consisting of 3 “alpha” polypeptide chains arranged in triple helix. Each chain is a single gene product, either 3 identical alpha chains (homotrimer) or two or more different alpha chains (heterotrimer).
Very stable and slowly tuned over.
Structure of fibrillar collagen
Each molecule of fibrillar collagen is made of 3 intertwined (triple driver) polypeptides.
Unique amino acid composition of Gly-X-Y repeats (X = often proline, Y = often hydroxyproline).
Tight packing of triple helix depends on glycine (or alanine) being very third residue.
Proline and hydroxyproline provide rigidity and stability.
Stabilised by hydrogen bonds between chains.
what is proline and lysine hydroxylation dependent on?
Vitamin C (ascorbate)
Bc the reaction is catalysed by an enzyme which requires vitamin C.
How does vitamin C deficiency cause scurvy?
Reduces collagen hydroxylation.
Reduced hydroxylation of proline weakens collagen triple helix.
Weaker collagen fibrils leads to scurvy = bleeding gums, loss of teeth, skin lesions, bruises, poor wound healing, joint pain and weakness.
What is the composition and organisation of collagen in different connective tissues?
Skin = mainly type I, some type III, mesh work of fibres.
Tendon/ligament = mainly type I, some type II, parallel fibres.
Bone = mainly type I, some type V, sheets (lamellae).
Cartilage = mainly type II, meshwork.
What provides tensile strength (in tendons)?
Type I collagen fibres arranged in parallel bundles.
What is the composition and organisation of the matrix of enthesis?
Enthesis structure varies along its length.
What are the changes associated with tendonopathy?
Loss of collagen fibril organisation and reduced fibril diameter.
Changes in collagen content - increases type II collagen, increased turnover.
Vascular ad nerve infiltration (painful tendons only).
Failure to repair (mechanical damage that caused problem difficult to release).
