Ramsha Khalid

M.Phil./Ph.D.
Biochemistry
 CARTILAGE

Cartilage is a supporting connective tissue

together with the bone, forms the framework supporting the body as a
whole.
There are many distinct types of cartilage
Among them, articular cartilage is the best known and the most studied
type.
Articular cartilage is the thin layer of connective tissue
covers the articulating ends of bones in synovial (diarthrodial) joints.

It provides a smooth surface for joint movement and acts as a load-bearing

medium that protects the bone and distributes stress.
 CARTILAGE
Stands up to both tension (stretching) and compression
Qualities intermediate between dense connective tissue (very flexible) and
bone
Tough but flexible, providing a resilient rigidity to the structures it supports

Lacks nerve fibers and is avascular

Receives its nutrients by diffusion from blood vessels located in the connective
tissue membrane (perichondrium) surrounding it

Ground substance contains large amounts of:

GAGs: glycosaminoglycans (Chrondroitin sulfate, Hyaluronic
acid):Intertwine and trap water, forming a substance that varies from
a fluid to a viscous gel
Contains firmly bound collagen fibers and in some cases elastic fibers
Matrix contains an exceptional amount of tissue fluid (up to 80% water)
Movement of tissue fluid in its matrix enables cartilage to rebound after being
compressed and also helps to nourish the cartilage cells
 Because cartilage is avascular and aging
cartilage cells lose their ability to divide,
cartilages heal slowly when injured
 During later life, cartilages tend to calcify or
even ossify (become bony)
 In such cases, the chondrocytes are poorly nourished
and die
 Elastic cartilage is found where strength and
exceptional stretchability are needed, such as the
external ear
 More elastin fibers
 Found where strength and exceptional stretchability
are needed
 Fibrocartilage is found where strong support
and the ability to withstand heavy pressure
are required, such as the intervertebral disks
 Often found where hyaline cartilage meets a true
ligament or a tendon
 Perfect intermediate between hyaline cartilage and
dense regular connective tissues
 Found where strong support and the ability to
withstand heavy pressure are required
 Cartilage Defects

 acute trauma

 Osteochondritis dissecans

 Osteonecrosis

 Osteoarthritis
 PRINCIPLES OF GENE THERAPY
Gene therapy is based on the principle that
proteins *therapeutic candidates
Gene therapy is simply the insertion of a gene into a cell so
that the cell now manufactures (through transcription and
then translation) the desired protein.

The concept of using gene transfer strategies for cartilage

repair originates from the idea of transferring genes
encoding therapeutic factors into the repair tissue, resulting
in a temporarily and spatially defined delivery of therapeutic
molecules to sites of cartilage damage
In Vivo
SELECTION OF GENES FOR GENE THERAPY
Insulin-like growth factor I (IGF-I)
Stimulates synthesis by chondrocytes of the two major building blocks of
articular cartilage: aggrecan and type II collagen

stimulatory effect on chondrocyte proliferation and inhibits chondrocyte

degradation of its surrounding matrix

Fibroblast growth factor 2 (FGF-2)

Transforming Growth Factor (TGF-b) TGF-β1 and TGF-β2
bone morphogenetic proteins (BMPs) BMP-2, BMP-7,
growth/differentiation factor 5 (GDF-5)
parathyroid hormone–related protein (PTHrP)
Cartilage derived morphogenetic proteins (CDMP)
SELECTION OF GENES FOR GENE THERAPY

Transcription factors
 SOX9

 Cbfa-1/Runx-2,68 Cart-1

Cytokines

 interleukin-1 (IL-1), IL-17

 Tumor necrosis factor (TNF)
 REGENERATION

Regeneration of a normal structural and functional cartilage

might be achieved by the following:
Transfected Xenogenic Cells for Cartilage Repair

Horses are widely used as large animal preclinical models for

cartilage repair studies

synovial fluid-derived mesenchymal stem cells (SFMSCs)

bone marrow-derived MSCs (BMMSCs)