Collagenase, procollagenase and bone resorption. Effects of heparin, parathyroid hormone and calcitonin.
1. The addition of heparin to the culture fluid of mouse tibiae or calvaria did not cause any significant resorption of bone collagen or mineral. However, heparin (or analogue sulfated polyanions), enhanced greatly the amount of latent, trypsin-activatable collagenase (i.e. procollagenase) released by the bones in the medium without influencing that of directly active collagenase which was always very low. Heparin appeared to act by increasing the production of the enzyme which is immediately excreted. Procollagenase and collagenase are not stored in bone tissue, even under conditions where it is in active resorption. 2. Parathyroid hormone induced in the explants a resorption of both mineral and collagen that was inhibited by calcitonin. These hormones, however, had no influence on the release of procollagenase or collagenase either in the presence or in the absence of heparin. 3. Once activated, bone collagenase digested the collagen of the bone explants, and more extensively after their demineralization. Thus the latent collagenase that accumulates around non-resorbing bones has to be considered as a precursor, (and not as a residue), of active enzyme. 4. Active collagenase added to incipient cultures of bones disappeared with a half-life of 24 h. The lost enzyme could, however, not be reactivated by trypsin and thus was not transformed into latent procollagenase.
D000818:Animals; D001862:Bone Resorption / Q000187:drug effects*; D001842:Bone and Bones / Q000187:drug effects / Q000378:metabolism*; D002116:Calcitonin / Q000494:pharmacology*; D002478:Cells, Cultured; D003513:Cycloheximide / Q000494:pharmacology; D004789:Enzyme Activation; D004792:Enzyme Precursors / Q000378:metabolism*; D006025:Glycosaminoglycans / Q000494:pharmacology; D006493:Heparin / Q000494:pharmacology*; D007700:Kinetics; D051379:Mice; D003012:Microbial Collagenase / Q000378:metabolism*; D010281:Parathyroid Hormone / Q000494:pharmacology*; D014357:Trypsin / Q000378:metabolism
D004792:Enzyme Precursors; D006025:Glycosaminoglycans; D010281:Parathyroid Hormone; D006493:Heparin; D002116:Calcitonin; D003513:Cycloheximide; D014357:Trypsin; D003012:Microbial Collagenase