Biochemistry of Connective Tissue

Question 1

Connective Tissue

Answer 1

• Supports and physically connects other tissues and cells together to form the organs of the body

Loose connective tissue -hold organs in place, attaches epithelia to adjacent tissues.

Dense connective tissue -tendons and ligaments, made up mostly of collagen fibres

Specialised connective tissues - adipose tissue, cartilage, bone, blood, and lymph.

Question 2

Resident Cells

Answer 2

• Synthetise the ECM
• Large amount of rough ER and Golgi apparatus to cope with the metabolic demands
• Fibroblasts
• Chondroblasts (cartilage)
• Osteoblasts (bone)
• Odontoblasts (tooth)
• Mast cells and macrophages: aggregate around blood vessels and critical to immune response

Question 3

Protein of ECM

Answer 3

Collagen - Most abundant, 30% of body protein content

Elastin - associated with other proteins. In arteries, lung, bladder, skin

Laminin - vital for the maintenance and survival of tissues. Binds to collagen. Defects lead to muscular dystrophy and epidermolysis bullosa

Fibronectin protein dimer, soluble and insoluble. Insoluble in ECM

Question 4

Collagen

Answer 4

• For firmness
• Composed mostly of glycine linked to proline or lysine or alanine
• Contains the modified amino acids 4-hydroxyproline and 5-hydroxylysine. Without them collagen would melt at body temperature

Question 5

Glycoproteins

Answer 5

Protein with carbohydrates attached
- Attachment of cells to extracellular matrix
- Organization of the compounds of extracellular matrix
- Ensure specific interactions between cells and molecules of extracellular matrix.

Question 6

Elastin

Answer 6

• helps tissues return to their original shape after stretching
• it is made as a pro-protein and is processed into fibres outside the cell

Question 7

Proteoglycans

Answer 7

Carbohydrates with protein attached
- 95% Glycosaminoglycans (GAG)
- GAG is synthesized first and the peptide attached to it
- Linear Polymers
- Sulphated GAGs form in Golgi app
- Non-sulphated GAGs form in plasma membrane

Question 8

Hyaluronic Acid (GAG)

Answer 8

• Non sulphated GAG
• Major component of the cartilage in articulations, synovial fluid, skin
• Contributes to tissue hydrodynamics, movement, proliferation and skin healing

Question 9

Chondroitin Sulphate

Answer 9

• Variable chain length and sulphation patterns
• Found as dietary supplement but not readily absorbed by gut

Question 10

HEPARAN/KERATAN SULPHATE

Answer 10

HS:
- Found in all animal tissues, binds to many extracellular proteins
KS:
- Biomechanical role in shock absorption
- In cartilages, bones, cornea and CNS

Question 11

GLYCOSAMINOGLYCAN DEGRADATION

Answer 11

• In lysosomes
• Enzymes breakdown to sulphated oligosaccharides
• Followed by exohydrolase activity to produce monosaccharides and inorganic sulfate
• Any defect in the sequence of degradation leads to incurable diseases, caused by the accumulation of intermediates

Question 12

Collagen Structure Formation

Answer 12

Inside Cell:
1) Transcription
2) Pre-pro-peptide to pro-peptide transition
3) Addition of oligosaccharides in the Golgi.

Outside Cell:
1) Collagen peptidases remove the N and C-termini from the procollagen = Tropocollagen
2) Lysine residues are activated and allow for assembly of collagen fibrils
3) Collagen fibrils are then linked into fibres

Question 13

Bone

Answer 13

• Mineralised connective tissue
• Supports and protects the body and internal organs
• Bone is a metabolically active tissue, continuously remodelled
• Buffers blood pH
• Stores and exchanges key biochemically relevant ions

Osteonectin => glycoprotein secreted by osteoblasts, Binds to collagen and promotes its mineralisation
Over expression in many cancers

Question 14

Bone Cells

Answer 14

Question 15

Bone + Calcium Homeostasis

Answer 15

Controlled by parathyroid hormone (PTH) and calcitriol
- PTH causes net bone loss (resorption) when administered continuously by increasing osteoclast activity
- PTH causes net bone formation (deposition) when administered intermittently by stimulating osteoblasts

Question 16

Inherited Diseases

Answer 16

Ehlers-Danlos syndromes: fragile and stretchy skin, joint hypermobility, problems with internal organs included fragile blood vessels

Marfan syndrome: exceptionally flexible joints, curved spine, problems with heart, blood vessels, eyes inc. blue sclera, lungs, bones

Autoimmune - Excessive collagen

Question 17

Osteomalacia

Answer 17

• Soft bones resulting from calcium absorption problems
• Mostly due to Vitamin D deficiency and imbalance of calcium and phosphorus
• Leading to fractures and muscle weakness

Question 18

LOOSE AND DENSE CONNECTIVE TISSUES AGING

Answer 18

Intrinsic aging - due to the progressive slow down of the production of these molecules
Extrinsic aging - caused by sun and environmental damage
- Loss of collagen, elastin and GAGs leads to less supported skin, tendons and ligaments
- The tissues become loose and brittle. They harden and shorten
- Higher risks for infection, smaller range of movements

Question 19

Osteoarthritis

Answer 19

Irreversible loss of collagen lining the joints from biochemical degradation of collagen and proteoglycans

Caused by:
- aging, weak muscles, joint injury,

Question 20

Osteoporosis

Answer 20

Porous bones
- bone mass decreases
- Decreased mineral density
- Deterioration of the bone matrix by increased resorption

Question 21

Causes of osteoporosis

Answer 21

• Decrease of oestrogens
• hyperthyroidism, hyperparathyroidism

Question 22

BONE, CARTILAGE AND THYROID HORMONES

Answer 22

Bone remodelling cycle (by osteoclasts and osteoblasts) is regulated by T3 and T4 thyroid hormones