Collagen Metabolism

Robert F. Diegelmann, PhD, From the Medical College of Virginia, Virginia Commonwealth University, Richmond, Virginia

Wounds. 2001;13(5) 

In This Article

Collagen Degradation

Of equal importance in the total picture of collagen metabolism is the complex process of collagen degradation. Normally, the collagen in our connective tissues turns over at a very slow and controlled rate. However, during rapid growth and in disease states, such as arthritis, cancer, and chronic nonhealing ulcers, the extent of collagen degradation can be quite extensive. In normal healthy tissues where the collagen is fully hydroxylated and in a triple helical structure (Figure 1), the molecule is resistant to attack by most proteases. Under these normal healthy conditions, only specialized enzymes called collagenases can attack the collagen molecule.[27] The group of collagenases belong to a family of enzymes called matrix metalloproteinases or MMPs.

Many cells in our bodies can synthesize and release collagenase including fibroblasts, macrophages, neutrophils, osteoclasts, and tumor cells. One of the reasons that some neoplastic cells can be so invasive is because they release potent collagenases and can break down the collagen around them. Then they can break down the basement membranes of blood vessels and spread throughout the body. In chronic pressure ulcers, there is a massive invasion of neutrophils, and they release a very potent collagenase called MMP-8 that is responsible for connective tissue breakdown.[28] Some exciting new research suggests that members of the tetracycline family of antibiotics, such as doxycycline, when given systemically, may be useful to treat pressure ulcers, because at low doses, they inhibit MMP-8.[29]