Osteopetrotic (grey-lethal) bone produces collagenase and TIMP in organ culture: regulation by vitamin A

Biochem Biophys Res Commun. 1990 May 16;168(3):1171-6. doi: 10.1016/0006-291x(90)91152-i.


Evidence has recently accumulated suggesting that osteoblasts play a direct role in bone resorption by producing collagenase. In this paper we describe studies carried out with explants of bone from osteopetrotic grey lethal (gl/gl) mice and show that despite the lack of osteoclastic activity the production of both active and latent collagenase and its specific inhibitor TIMP (tissue inhibitor of metalloproteinases) is similar to that of normal bones. Synthesis of collagenase was stimulated by the bone resorptive agent vitamin A (retinol); concomitantly, TIMP levels fell to zero and active enzyme was detected in the culture medium. This work supports the view that bone collagenase is produced by cells other than osteoclasts, since the response of the osteoblastic population to resorptive signals appears normal.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bone Resorption / metabolism
  • Bone and Bones / drug effects
  • Bone and Bones / metabolism*
  • Calcium / metabolism
  • Chromatography, Gel
  • Culture Techniques
  • Glycoproteins / biosynthesis*
  • Mice
  • Mice, Mutant Strains
  • Microbial Collagenase / biosynthesis*
  • Osteopetrosis / metabolism*
  • Tissue Inhibitor of Metalloproteinases
  • Vitamin A / pharmacology*


  • Glycoproteins
  • Tissue Inhibitor of Metalloproteinases
  • Vitamin A
  • Microbial Collagenase
  • Calcium