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.