Collagenases in Health and Disease

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Collagenases in Health and Disease

• Bone Remodeling
• Wound Healing
• Resorption of uterine lining
• Cancer
• The first three are essential for maintaining
  normal health

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Hyaluronic Acid
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COLLAGEN TRIPLE HELIX
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Fibrous Proteins-Collagen

• INSOLUBLE
• STABLE
• LONG BIOLOGICAL HALF-LIFE
• HIGH TENSILE STRENGTH OR CONTRACTIBILITY

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Localization of macromolecules associated with
calcification in mammals
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Ground Substance Organization
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Synthesis and Processing of collagens
DNA
mRNA
PreProcollagen
Procollagen polypeptide
Hydroxylation of Prolines and Lysines
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Synthesis of Collagen-continued
Hydroxylated prolines and lysines
ProCollagens
Prolyl Hydroxylases and Lysyl Hydroxylase
Cofactor Vitamin C and Molecular O2 is
essential Two Prolyl Hydroxylases ( hydroxylating
3 and 4 positions of prolines and one lysyl
Hydroxylase In Sequence --GlyXY-- Y residue
is the one that is hydroxylated
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Hydroxylated ProCollagens
Glycosylated ProCollagens Selected OH-lysine and
Asn (asparagine) residues are Glycosylated
Add N- and C-Terminal extension containing many
CYS
Formation of Triple Helix in the cell
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Intracellular
Triple Helix of Procollagen
Extracellular
Procollagen Bundles
Procollagen Peptidase
Collagen Fiber
Lysyl Oxidase O2, Cu
Formation of Cross-links
Mature Cross-linked Collagen Fiber
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Oxidation and Cross-Linking of Lysines and
Hydroxylysines
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Classification of Collagens
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Classification Continued
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Regulation of osteoblast function by hormones and
growth factors

• Growth hormone, growth factors and 24,25 (OH)2 D3
  Promote synthesis and secretion of
• type I collagen
• GLA proteins
• Alkaline phosphatase
• Factors that promote maturation of preosteoblasts
• TGF-beta
• Estrogen and calcitonin appear to inhibit
  maturation of osteoclasts

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Bone resorbing actions of PTH, 1,25 (OH)2D3 and
Cytokines

• PTH
• Probably induces factors in osteoblasts which
  increase the maturation of osteoclasts
• Increases production of collagenase IV in
  osteoclasts
• 1,25 (OH)2 D3
• stimulates collagenase and inhibits collagen
  production in osteoblasts
• Cytokines
• Promote collagenase production and inhibit
  collagen production by osteoblasts

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Clinical testing of increased collagenase 8
(interstitial collagenase) in GCF strips is
indicator of periodontal disease
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