Matrix Metalloproteinases (MMPs)
and the Extracellular Matrix (ECM)

Body tissues are made of cells and extracellular matrix (ECM).  The ECM is a general term referring to structural compenents of tissues and occurring more abundantly in cartilage, the fibrous sheaths of muscles, tendons and ligaments, the dermal layer of the skin and bones, etc.  The ECM is composed of a complex network of proteins such as collagen or elastin linked with polysaccharides such as glycosaminoglycans (in the case of bones, minerals are added). As its names implies the ECM is secreted by cells (that is why it is called “extracellular”) (Alberts et al, 1994).

  All of these ECM components are in constant renewal, or turnover, a process based on equilibrium of breakdown and rebuilding. Breakdown (catabolism) is the result of catabolic enzymes such as proteinases, while rebuilding (anabolism) is the work of numerous anabolic enzymes that synthesize the macromolecular components of the ECM.  When there is an overabundance of catabolic activity relative to synthesis the imbalance can lead to the deterioration of the ECM which is linked to conditions as varied as arthritis, muscle pain or psoriasis.

Catabolism is the work of catabolic enzymes known as collagenases or matrix metalloproteinases (MMPs), which cleave the fibrous proteins of the ECM (Parks and Mecham, 1998).

In addition to their role in breaking down cartilage, muscles, tendons, skin and other tissues, MMPs have also been shown to be involved in angiogenesis, or new blood vessel formation (Moses, 1992). Like MMPs, angiogenesis itself has been linked with numberous diseases and conditions (Folkman, 1995). For a new blood vessel to form, endothelial cells from an existing blood vessel must proliferate, cross the basement membrane and migrate into surrounding tissues.  In order to do this, endothelial cells must product MMPs.  Therefore, the inhibition of MMP activity has been identified as a means of inhibiting blood vessel formation or angiogenesis.

With aging and in various conditions, the metabolic activity of cells such as chondrocytes and fibroblasts may become disturbed.  Such a disturbance may affect the equilibrium between production and breakdown of extracellular matrix (ECM) (Murphy and Reynolds, 1993).  In these conditions, the balance between MMPs and inhibitors of MMPs is not longer respected so that, in most cases, the enzymatic activity of MMPs predominates.

Aging, long-term sunlight exposure and mechanical stressing of joints are all factors associated with an increased enzymatic activity of MMPs (Fisher, 1997).  This activity eventually leads to the degradation of the collagen fiber meshwork.  Because of its involvement in the angiogenic process, increased activity of MMPs may also contribute to uncontrolled angiogenesis.

Nutritional supplementation with MMP inhibitors may reestablish the enzymatic equilibrium. Cartilade supports healthy connective tissues and joints by its profile of natural macromolecules, glycosaminoglycans, chondroitin, and Type II collagen. Cartilade also contains the most potent MMP inhibition of cartilage powders and other joint health ingredients as tested by in vitro assays.

REFERENCES

Murphy G and Reynolds JJ: Extracellular matrix degradation. In: Connective tissues and its heritable disorders; 1993:287-316, Wiley-Liss, New York, NY.

Fisher GJ et al.; Pathophysiology of premature skin aging induced by ultraviolet light. N Engl J Med 1997:337: 1419-1428.

Alterts B, Bray D, Lewis J, Raff M, Roberts K, and Watson JD: Molecular biology of the cell, 3rd ed. 1994; Garland Publishing, New York, NY

Parks WC and Mecham RP: Matrix metalloproteinases. 1998: Academic Press, San Diego, California

Moses MA and Langer R: Metalloproteinase inhibition a a mechanism for the inhibition of angiogenesis.  In: Angiogenesis: Key Principles; Steiner R, Weisz RB, Langer R, eds, 1992 Birkhauser Verlag, Basel, Switzerland.

Folkman, J: Clinical applications of research on angiogenesis.  New Engl J Med 1995;333(26): 1757-1763.