Collagen Abnormalities

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Collagen Abnormalities

  1. 1. Collagen Abnormalities Congenital, Metabolic & Age-related phenomena
  2. 2. Congenital Osteogenesis imperfecta
  3. 4. The biochemical basis of OI
  4. 5. Metabolic & Age-related alterations to collagen <ul><li>Why is collagen vulnerable? </li></ul><ul><li>long lived protein </li></ul><ul><li>Susceptible to modification </li></ul><ul><li>Turnover/renewal and function of tissues are compromised </li></ul><ul><li>Diabetes will result in collagen changes </li></ul>
  5. 6. Diabetes & collagen changes <ul><li>Glycation – modified amino acids </li></ul><ul><li>– e.g., pentosidine, N-carboxymethylarginine </li></ul><ul><li>Lipid peroxidation </li></ul><ul><li>Malondialdehyde, product of FA oxidation, also reacts with some collagen cross-links (Slatter et al. 1999) </li></ul><ul><li>Collectively they alter the material properties (e.g., stiffness) and proteolytic susceptibility. </li></ul>
  6. 7. N-Carboxymethylarginine
  7. 8. Metabolic bone diseases
  8. 9. What are the changes? <ul><li>Bone collagen accumulation </li></ul><ul><li>Raised bone collagen turnover </li></ul><ul><li>Very large increases in PICP </li></ul><ul><li>Large increases in catabolic enzymes </li></ul><ul><li>Hypomineralised collagen </li></ul><ul><li>Cartilage splitting, cartilage loss </li></ul>
  9. 10. Osteoporosis
  10. 11. Paget’s Disease

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