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Overview
  • Collagen is a naturally occurring family of proteins
    • over 25 types of collagen have been described
  • Makes up the most abundant type of protein found in humans
    • ~25% of the whole-body protein content is composed of some type of collagen
    • found in multiple tissues like cartilage, tendon, bone, ligament, skin (see table below)
    • multiple different forms of collagen exist, each with different biomechanical properties suited to the environment in which that form is expressed
  • Collagen is made of elongated fibrils formed by fibroblast cells
    • synthesis of collagen is unique in that it occurs both inside and outside the cell
Biochemisty
  • Composition
    • collagen is composed of a triple helix of 
      • two alpha1 chains
      • one alpha2 chain 
    • several common amino acid sequences are found in collagen including 
      • Glycine-X-Hydroxyproline
      • Glycine-Proline-X 
  • Formation of collagen fibers 
    1. alpha chains
      • three alpha chains (two alpha1 and one alpha 2) are formed
    2. procollagen
      • two alpha1 and one alpha2 combine to form procollagen
    3. tropocollagen
      • procollagen is processed by extracellular protein modification into a tropocollagen molecule after being expressed from the golgi apparatus
    4. collagen fibril
      • aldehyde formation on tropocollagen lysine and hydroxylysine allow for covalent bonding between tropocollagen molecules forming the collagen fibril 
    5. collagen fiber
      • multiple collagen fibrils aggregate to form a collagen fiber
Types of Collagen
 
          Type            
Location
I
II
III
IV
V
VI
VII
VIII
IX
X
XI
Bone
o
                   
Ligament o                    
Tendon o                    
Meniscus o                    
Disc - Annulus o                    
Disc - Pulposus   o                  
Cartilage - Articular   o     o o     o    
Cartilage - Basement Membrane       o              
Cartilage - Deep calcified layer o                 o  
Cartilage - Reparative(fibrocartilage)  o  o                  
Skin o   o                
Blood Vessels     o                
Epithelial Basement Membrane             o o      
Collagen lattice                     o
 
  • Type I Collagen
    • accounts for more than 90% of the total collagen content in the body
    • found in
      • bone
      • ligament
      • tendon
      • meniscus
      • annulus of intervertebral disks
      • skin
      • healed cartilage
      • scar tissue
      • nerves s
    • related clinical conditions
      • osteogenesis imperfecta 
      • Ehlers-Danlos syndrome 
  • Type II Collagen  
    • is found
      • articular (hyaline) cartilage
      • nucleus pulposus of intervertebral disks
    • type II collagen has a very long half life
  • Type III Collagen
    • found in skin and blood vessels
    • related clinical conditions
      • Ehlers-Danlos syndrome 
      • Dupuytren's contracture 
  • Type IV Collagen
    • found in basement membranes
    • related clinical conditions
      • renal diseases like Goodpasture's and Alport syndromes
  • Type V, VI, IX Collagen
    • occur in small amounts in articular cartilage
    • type IX collagen gene deletion linked to development of OA in women and in knockout mice
    • mutations in COL9A1, COL9A2, COL9A3 linked to multiple epiphyseal dysplasia (MED)
      • however 70% of MED is associated with COMP
      • fragmented ossific centers
      • coxa vara hips  
      • genu valgum   
      • shortened, stunted metacarpals  
  • Type VII and VIII Collagen
    • basement membrane (epithelial)
  • Type X Collagen
    • is found in the deep calcified layer of cartilage
    • produced only by hypertrophic chondrocytes during enchondral ossification (growth plate, fracture callus, heterotopic ossification) 
      • associated with calcification of cartilage in the deep zone of articular cartilage
    • increased in early arthritis
    • related clinical conditions
      • Schmid metaphyseal chondrodysplasia 
  • Type XI Collagen
    • an adhesive with the function of holding the collagen lattice together in cartilage
 

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