Matrix metalloproteinases and lysosomal cysteine proteases in osteoclasts contribute to bone resorption through distinct modes of action

Biochem Biophys Res Commun. 1999 Apr 29;258(1):173-8. doi: 10.1006/bbrc.1999.0473.


The effects of inhibitors of matrix metalloproteinases (MMPs) and lysosomal cysteine proteases on osteoclastic pit formation in dentine slices were investigated. A nonspecific cysteine protease inhibitor, E-64, inhibited pit formation on naked slices in a concentration-dependent manner, and at 10 microM E-64 reduced the pit volume by 70%. However, up to 10 microM of the MMP inhibitor, BB-94, did not show any inhibition of pit formation. On the other hand, on slices coated with reconstituted basement membrane, both BB-94 and E-64 at 10 microM showed a marked decrease in pit volume by 73% and 68%, respectively. By a combination of treatment with both BB-94 and E-64, pit formation could be completely suppressed. These results suggest that MMPs are necessary for the migration of precursor and/or immature osteoclasts to bone surface through basement membranes, while cysteine proteases are essential for the osteoclastic degradation of bone collagen.

MeSH terms

  • Animals
  • Base Sequence
  • Bone Resorption*
  • Cysteine Endopeptidases / metabolism*
  • DNA Primers
  • Leucine / analogs & derivatives
  • Leucine / pharmacology
  • Lysosomes / enzymology*
  • Metalloendopeptidases / antagonists & inhibitors
  • Metalloendopeptidases / metabolism*
  • Osteoblasts / cytology
  • Osteoblasts / drug effects
  • Osteoblasts / enzymology
  • Phenylalanine / analogs & derivatives
  • Phenylalanine / pharmacology
  • Protease Inhibitors / pharmacology
  • Rabbits
  • Reverse Transcriptase Polymerase Chain Reaction
  • Thiophenes / pharmacology


  • DNA Primers
  • Protease Inhibitors
  • Thiophenes
  • Phenylalanine
  • batimastat
  • Cysteine Endopeptidases
  • Metalloendopeptidases
  • Leucine
  • E 64