What controls collagen resorption in vivo?

The local control of collagen degradation in mammals in vivo is currently considered to depend primarily on variations on the level of activity of specific collagenases. Such variations are believed to depend on three factors: a) the rate of active collagenase synthesis and/or of activation of inactive enzyme precursors; b) the action of serum and/or tissue collagenase inhibitors; and c) different combinations of both mechanisms. We suggest that another element contributing to the regulation of collagen degradation in vivo is the susceptibility of the substrate. Support for this suggestion is derived from two sources: 1) experimental data, indicating that the rate of collagen degradation depends on the genetic type of substrate, on its state of aggregation (including degree of cross-linking), and on the nature and amount of other macromolecules associated with collagen in vivo. Other experimental findings supporting our hypothesis are the universal presence of collagen-bound collagenase, the apparent greater affinity of the enzyme for the more recently synthetized substrate molecules, and the increased amounts of intact collagen that may be solubilized from some tissues undergoing massive collagen degradation, 2) analogy with currently accepted views on intracellular protein catabolism, which cannot be rejected a priori as irrelevant to the problem.