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BIOCHEMISTRY OF CARTILAGE

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BIOCHEMISTRY OF CARTILAGE Structure of proteoglycans The GAGs extend perpendicular from the core protein in a bottlebrush- like structure. The linkage of GAGs to ... – PowerPoint PPT presentation

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Title: 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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