BIOCHEMISTRY OF CARTILAGE

BIOCHEMISTRY OF CARTILAGE

DEFINITION Specialized form of connective tissueconnective tissue

with firm consistency of extra-cellular matrixfirm consistency of extra-cellular matrix, allow the tissue to bear mechanical stressesbear mechanical stresses without permanent distortion and Support soft tissues .Support soft tissues .

Sliding areas for joints to facilitate movement Sliding areas for joints to facilitate movement Provides a model for the formation of most of model for the formation of most of

the bones in the bodythe bones in the body..

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

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.

Epithelial cells

extra-cellularmatrix

Underlying cells

The extracellular matrix is composed of an interlocking meshwork of heteropolysaccharides and fibrous proteins.

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

• 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.

• 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).

Structure of Glycosaminoglycans

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

CHONDROCYTES

Cells that synthesizesynthesize and secrete Extracellular

Matrix

The cells are located in matrix cavity called Lacunae

CHONDROCYTES

EXTRACELLULAR MATRIX (25%)(25%)

FibersFibersCollagen (II)Collagen (II)Elastin Elastin fibrillin fibrillin

Ground substances Ground substances Proteoglycan (Aggregan)Proteoglycan (Aggregan)Glycoprotein Glycoprotein

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.

FIBRES CREATES A FRAMEWORK THAT HOUSES THE OTHER COMPONENTS OF CARTILAGE

COLLAGEN (15%)Majority (90-98%) is Type II collagen.

Provides cartilage with its tensile strength

Compressiveproperties

Fluid flow

GROUNDSUBSTANCE

Highly hydrated complexhydrated complex of mixture of proteoglycans and glycoproteins

Proteoglycans are linear polysaccharideslinear polysaccharides of repeating disacchariderepeating disaccharide units composed of hexosamine & uronic acidGlucosamine/GalactosamineGlucoronic acid/Iduronic acid

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).

PROTEOGLYCAN: PROTEIN WITH BOUND SIDE CHAINS (GLYCOSAMINOGLYCANS

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

Hyaluronic acid (D-glucuronate + GlcNAc)

2) Chondroitin sulfate(D-glucuronate + GalNAc sulfate)It is the most abundant GAG. cartilage, tendon, ligament, and walls of the aorta

Dermatan sulfate (L-iduronate + GlcNAc sulfate)

Occurence : skin, blood vessels, heart valves

Heparin - natural anticoagulant made in mast cells bind antithrombin, then bind and inhibit thrombin

Keratan sulfate ( Gal + GlcNAc sulfate) Occurence : cornea, bone, cartilage ; Keratan sulfates are often aggregated with chondroitin sulfates.

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.

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

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!

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)

• 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)

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

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