Collagenolysis

Collagenolysis is the enzymatic breakdown of collagen, the main structural protein of the extracellular matrix. The process enables remodeling of connective tissues and is carried out by collagenases, proteases capable of cleaving the native collagen triple helix at a defined site. In humans, the principal collagenases are matrix metalloproteinases MMP-1 (collagenase-1), MMP-8 (collagenase-2), and MMP-13 (collagenase-3). These enzymes are secreted as inactive zymogens and require proteolytic activation and the presence of zinc and calcium ions for activity. Their action yields two collagen fragments that are subsequently degraded by other proteases. Collagenolysis is tightly regulated by tissue inhibitors of metalloproteinases (TIMPs) and by transcriptional control, signaling pathways, and localization within the extracellular matrix.

In physiological contexts, collagenolysis participates in normal development, wound healing, tissue remodeling, bone turnover, and angiogenesis. In pathology, excessive or mislocalized collagenolysis contributes to inflammatory diseases such as rheumatoid arthritis and osteoarthritis, to fibrosis, and to cancer invasion and metastasis by enabling tumor cells to move through extracellular matrix barriers. Bacterial collagenases also exist, notably from Clostridium species, and are used in medical and industrial applications because of their ability to degrade collagen.

Measuring collagenolysis involves assessing MMP activity or the production of collagen fragments, and therapeutic strategies often aim to modulate MMP activity or the balance of TIMPs. Clinical modulation remains complex due to the broad roles of collagenases in normal physiology and disease.