BIOCHEMISTRY OF CARTILAGE

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BIOCHEMISTRY OF CARTILAGE
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• DEFINITION
• Specialized form of
  connective tissue with firm consistency of
  extra-cellular matrix, allow the tissue to bear
  mechanical stresses without permanent distortion
  and Support soft tissues .
• Sliding areas for joints to facilitate
  movement Provides a model for the formation of
  most of the bones in the body.

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TYPES OF CARTILAGES

• HUMAN BODY HAS THREE TYPES OF CARTILAGES
• Hyaline Cartilage
• articular cartilage
• larynx
• rib and costal cartilage
• nasal septum
• Elastic Cartilage
• epiglottis
• Fibrocartilage
• Intervertebral disk
• meniscus

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• The extracellular space in animal tissues is
  filled with a gel-like material, the
  extracellular matrix, also called ground
  substance,
• which holds the cells of a tissue together and
  provides a porous pathway for the diffusion of
  nutrients and oxygen to individual cells.

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Epithelial cells
extra-cellularmatrix
Underlying cells
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• The extracellular matrix is composed of an
  interlocking meshwork of heteropolysaccharides
  and fibrous proteins.

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• Heteropolysaccharides in the body are the
  glycosaminoglycans (GAGs). These molecules are
  long unbranched polysaccharides containing a
  repeating disaccharide unit.

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• The disaccharide units contain either of two
  modified sugars, called amino sugars
  N-acetylgalactosamine (GalNAc) or
  N-acetylglucosamine (GlcNAc),
• and an acidic sugar uronic acid such as
  glucuronic acid or iduronic acid.

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• GAGs are highly negatively charged molecules,
  with extended conformation that imparts high
  viscosity to the solution.
• GAGs are located primarily on the surface of
  cells or in the extracellular matrix (ECM).

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Structure of Glycosaminoglycans

• GAGs in the body are linked to core proteins (
  except hyaluronic acid), forming proteoglycans
  (also called mucopolysaccharides).

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CHONDROCYTES

• Cells that synthesize and secrete
  Extracellular
• Matrix
• The cells are located in matrix cavity
  called
• Lacunae

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CHONDROCYTES
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EXTRACELLULAR MATRIX (25)

• Fibers
• Collagen (II)
• Elastin
• fibrillin
• Ground substances
• Proteoglycan (Aggregan)
• Glycoprotein
•  

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• The chains are linear (unbranched)
• They are linked to the protein core via a
  serine or threonine (O-linked) (except HA)
  forming Proteoglycan.
• Negative charge due to OH, COOH, and SO4, PG
  are hydrophillic and act as polyanion attract
  ions (K and Na)
• Highly solvated and viscous.

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FIBRES CREATES A FRAMEWORK THAT HOUSES THE OTHER
COMPONENTS OF CARTILAGE
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GROUNDSUBSTANCE

• Highly hydrated complex of mixture of
  proteoglycans and glycoproteins
•  Proteoglycans are linear polysaccharides of
  repeating disaccharide units composed of
  hexosamine uronic acid
• Glucosamine/Galactosamine
• Glucoronic acid/Iduronic acid

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Linkage

• The linkage of GAGs to the protein core involves
  a specific trisaccharide composed of two
  galactose residues and a xylose residue
  (Gal-Gal-Xyl-O-CH2-protein).

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PROTEOGLYCAN PROTEIN WITH BOUND SIDE CHAINS
(GLYCOSAMINOGLYCANS
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HETERO POLYSACCHARIDES (GAG) OF THE
EXTRA-CELLULAR MATRIX

• Hyaluronic acid - glassy and translucent
• lubricants in joints, cartilage, and tendons
• hyaluronidase in pathogenic bacteria and sperm

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Hyaluronic acid (D-glucuronate GlcNAc)
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2) Chondroitin sulfate(D-glucuronate GalNAc
sulfate)It is the most abundant GAG.
cartilage, tendon, ligament, and walls of the
aorta
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Dermatan sulfate (L-iduronate GlcNAc sulfate)
Occurence skin, blood vessels, heart valves
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Heparin - natural anticoagulant made in mast
cells bind antithrombin, then bind and inhibit
thrombin
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Keratan sulfate ( Gal GlcNAc sulfate)
Occurence cornea, bone, cartilage Keratan
sulfates are often aggregated with chondroitin
sulfates.
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• Structure of proteoglycans
• The GAGs extend perpendicular from the core
  protein in a bottlebrush- like structure.
• The linkage of GAGs to the protein core
  involves a specific trisaccharide .The protein
  cores of proteoglycans are rich in Ser and Thr
  residues which allows multiple GAG attachment.

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• Much of the compressive strength of cartilage is
  derived from the glycosaminoglycan molecules in
  the extracellular matrix.
• These molecules have abundant carboxyl and
  sulfate groups that are negatively charged under
  physiologic conditions

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PROTEOGLYCAN FUNCTIONS

• Modulation of cell growth processes
• Binding of growth factor proteins by
  proteoglycans in the glycocalyx provides a
  reservoir of growth factors at the cell surface.
• Cushioning in joints
• Cartilage matrix proteoglycans absorb large
  amounts of water. During joint movement,
  cartilage is compressed, expelling water!

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• Some Functions of Glycosaminoglycans and
  Proteoglycans
• Act as structural components of the ECM Have
  specific interactions with collagen, elastin,
  fibronectin, laminin, and other proteins such as
  growth factors
• As polyanions, bind polycations and cations
• Contribute to the characteristic turgor of
  various tissues
• Act as sieves in the ECM Facilitate cell
  migration (HA)

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• Have role in compressibility of cartilage in
  weight-bearing (HA, CS)
• Play role in corneal transparency (KS I and DS)
• Have structural role in sclera (DS)
• Act as anticoagulant (heparin)
• Are components of plasma membranes, where they
  may act as receptors and participate in cell
  adhesion and cell-cell interactions (eg, HS)
• Determine charge-selectiveness of renal
  glomerulus (HS)
• Are components of synaptic and other vesicles
  (eg, HS)

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• When glycosaminoglycans are lost from the
  cartilage matrix, as occurs in trauma or
  osteoarthritis, the mechanical stiffness of the
  tissue is dramatically reduced, and the
  functional integrity of the cartilage is
  compromised.
• .

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• Maintaining and restoring glycosaminoglycans in
  adequate concentrations in the extracellular
  matrix are therefore important targets for
  therapeutic interventions.
• Understanding the loss and replenishment of
  glycosaminoglycans is potentially important in
  determining the correct diagnosis early,
  monitoring the disease, and selecting treatments

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