S3: Fibrous Extracellular Matrix Proteins: Tendons, Ligaments and Beyond

Question 1

What is the origin of connective tissue?

Answer 1

Mesodermal embryological origin

Question 2

What are the 3 dense forms connective tissue can have?

Answer 2

• Tough physical support in the dermis of the skin. - Capsules of organs - liver and spleen - Great tensile strength - ligament/tendons

Question 3

Describe extracellular matrix (ECM)

Answer 3

• Matrix of organic material embedded in a variety of fibres. - A dynamic and physiologically active component of all living tissues. - ECM largely determines the function and appearance of the tissues and all tissues have some level of ECM.

Question 4

What is in ECM?

Answer 4

• Ground substance - Fibrous proteins - collagen and elastin - Water - Minerals

Question 5

Describe ground substance found in ECM content

Answer 5

• Ground subsance is made of fibres and glycosaminoglycans (GAGs) which are part of tissues and linked with proteins. - GAGs and proteins form proteoglycans (mucoprotein). - Structural glycoproteins are the third constituent of the ECM mediate the interaction of cells with the other constituents. - Hyaluronic acid is the predominant GAG in loose supporting tissues and is the only one without sulphate side groups. It gives function and shape of tissues. - GAG is not flexible enough to form globular aggregates (unlike many proteins) so they remain in expanded form and take up huge volume for relatively small mass. - GAG is extremely hydrophilic thus attracting a large volume of water and positive ions (mainly Na+ which constitutes of ECF). The ECF imparts the characteristic turgor of connective tissue.

Question 6

List the fibrous proteins in ECM

Answer 6

• Collagen - Elastin

Question 7

What are fibroblasts?

Answer 7

They are fibre making cells. that make collagen and elastin - especially during inflammatory processes.

Question 8

Describe collagen in ECM

Answer 8

• Main type of fibre found in connective tissue and it is the most abundant protein in the human body. - Its most notable function is the provision of tensile strength. - Collagen is secreted into the extracellular matrix in the form of tropocollagen (3 polypeptide alpha chains). - ECM tropocollagen molecules polymerise to form collagen. - Collagen fibrils provide the ‘framework’ of connective tissue

Question 9

How many types of collagen are there and how are they delineated?

Answer 9

There are at least 16 types of collagen. They are delineated on the basis of morphology, physical properties and amino acid compositions.

Question 10

Give examples on how the 3D organisation of collagen fibrils determines mechanical properties of tissue

Answer 10

• Connective tissue: framework - Tendon/ligaments : parallel bundles - Bone: Spirals - Cartilage: Meshwork

Question 11

Three disorders due to mutations in collagen genes

Answer 11

Osteogenesis imperfecta is a type I collagen mutation. Achondrogenesis is a type II collagen mutation. Ehlers-danlos syndromes is a type III or V collagen mutation.

Question 12

Symptoms of ehlers-danlos sydrome

Answer 12

• Joint hyper-mobility - Skin hyperextensibility - Rupture of blood vessels - Generalized tissue fragility

Question 13

Describe elastin in ECM

Answer 13

• Elastin is a rubber like material which is arranged as fibres and/or discontinuous sheets in the ECM. - Particularly of skin, lung and blood vessels where it confers the properties of stretching and elastic recoil. - Elastin is synthesised by fibroblasts in a precursor form known as tropo-elastin which undergoes polymerisation in the extracellular tissues. - Deposition of elastin in the form of fibres requires presence of microgibrils composed of glycoproteins known as fibrillin. These microfibrils are essential for the integrity of elastic fibres.

Question 14

What two things influence elastin degradation?

Answer 14

• Elastase - Alpha-1-anti-trypsin (inhibits elastase)

Question 15

How is collagen and elastin affected in hypertension?

Answer 15

· In hypertension, there is increased synthesis and deposition of elastin and collagen in vessel walls (because of inflammation). Vessels are thickened so diameter of vessels are reduced. It is difficult to treat/recover because turnover of elastin and collagen is slow.

Question 16

What is pulmonary emphysema?

Answer 16

• Loss of elastin = reduced elasticity of the lungs - Sometimes due to deficiency of α1-anti-trypsin - α1-anti-trypsin normally inhibits elastase - Too much elastase = excessive degradation of elastin

Question 17

What is marfan syndrome?

Answer 17

• Mutation in elastin fibres associated gene - fibrillin gene - Affects the cardiovascular, ocular and skeletal system with aortic root dilation/dissection - Ectopia lentis and bone overgrowth - Like Marfan syndrome, Ehlers-Danlos syndrome is caused by a defect in the body’s connective tissue.