MMP1 Biology and Biochemistry

Interstitial collagenase is one of four collagenases able to degrade the interstitial collagens types I, II, and III at neutral pH (Table 4.1). MMP-8 (neutrophil collagenase),28 MMP-13 (collagenase-3),29 and MT1-MMP (membrane-type 1- MMP), a membrane bound form of the MMPs,30 are also members of the collagenase subfamily able to degrade collagen (Table 4.1), and their roles are described in chapter 1. The interstitial collagens (types I, II and III) are the most abundant proteins in the body,...

Inhibition of MMP1 Transcription

Because of the therapeutic implications, inhibiting MMP-1 has been a major focus of research. Reducing MMP-1 levels could prevent the irreversible degradation of cartilage, tendon, and bone in arthritis and impede the process of tumor migration and invasion in cancer. Considerable attention has, therefore, been directed at the inhibition of collagenase activity, with either naturally occurring protein inhibitors (the TIMPs) or with synthetic compounds. Alternatively, inhibition of MMP-1 can...

Collagen Degradation

A direct involvement of collagenases in type II collagen degradation was recently demonstrated in human articular cartilage.41 Antibodies were developed that recognize the carboxy-terminal and the amino-terminal neoepitopes generated by cleavage of native human type II collagen by the three collagenases 1, 2, and 3. When the antibodies were used to immunoassay cartilage extracts, significantly more neoepitope was present in OA cartilage compared to nonOA cartilages. The neoepitope reflecting...

Stephen M Krane and Weiguang Zhao MMPs with Collagenase Activity

In the process of remodeling of bone and other connective tissues, components of the extracellular matrix (ECM) such as collagens and proteoglycans are degraded and removed and new components are synthesized and deposited. The extent and intensity of remodeling is regulated by specific cells in each tissue that respond to signals from other cells and the matrix itself.1 Three main classes of enzymes have been implicated in the degradation of collagen, the most abundant component of the ECM. The...

References

The role of extracellular matrix metalloproteinases in connective tissue remodeling. In Fitzpatrick TB, Eisen AZ, Wolff K etal.,eds. Dermatology in General Medicine. 4th ed. New York McGraw-Hill, Inc. 1993 315-328. 2. Cawston TE. Metalloproteinase inhibitors and the prevention of connective tissue breakdown. Pharmacol Ther 1996 3 163-182. 3. Henderson B, Blake S. In Davies ME, Dingle JT, eds. Immunopharmacology of joints and connective tissue. London Academic Press...

Familiar Drugs in Novel Applications

Pharmaceutical agents that are recognized for efficacy in one clinical application occasionally find new life in another. One well known example is aspirin which, originally used for its analgesic, antipyretic and anti-inflammatory actions, now also plays a major role in management of vaso-occlusive diseases due to its antithrombotic actions. A similar set of discoveries has occurred for several commonly used drugs whose anti-collagenase properties have only recently been explored. A...

Pathological Significance of Human Collagenase3

To date, human collagenase-3 expression has been associated with two pressing pathological conditions cancer and arthritic diseases. In fact, collagenase-3 was originally identified as an enzyme produced by mammary carcinomas,1 but further studies have extended its participation to other tumor processes distinct from breast cancer. In addition, the relevance of collagenase-3 as a degradative enzyme in joint diseases has been the focus of notable interest, with a number of papers examining...

Summary and Conclusion

Cell-type and species-specific mechanisms regulate transcription of MMP-1. This regulation depends not only on the array of cis-acting sequences and their juxtaposition in the promoters of MMP-1 from different species, but also on the assortment of transcription factors found in these species and cell types. This concept is becoming increasingly apparent as MMP-1 gene expression is studied in a variety of cell types. The previous contributions made by investigators studying the crucial role of...