Matrix Metalloproteinase 13 (MMP13), also known as Collagenase-3, is an enzyme. Its primary function is to break down collagen, a protein providing structural support to tissues. MMP13 is particularly efficient at degrading type II collagen, a component of cartilage. This molecule has a dual nature; its activity is necessary for normal bodily processes, but when unregulated, it can contribute to several diseases.
The Normal Role of MMP13 in the Body
Normally, MMP13 is produced in low amounts and participates in processes requiring tissue remodeling. During fetal development, for example, it is involved in forming and shaping the skeleton. The enzyme helps break down temporary structures to make way for more permanent bone tissue.
MMP13 is also involved in tissue maintenance and repair, such as in wound healing. When tissues are damaged, the body must clear away the old structural framework to build a new one. MMP13 assists in this cleanup by degrading damaged collagen, which allows for the replacement of old tissue with new.
MMP13’s Role in Joint Disease
The function of MMP13 is linked to the health of articular cartilage, the smooth tissue covering the ends of bones within joints. In healthy joints, MMP13 activity is tightly controlled to balance cartilage breakdown and synthesis, ensuring the joint surface remains intact.
In diseases like osteoarthritis, this balance is disrupted. Inflammatory signals cause cartilage cells (chondrocytes) to increase their production of MMP13. This overproduction leads to excessive degradation of the collagen network within the cartilage. The breakdown of this framework compromises the cartilage’s integrity, causing it to thin and wear away.
As cartilage deteriorates, it loses its ability to cushion the joint, leading to osteoarthritis symptoms like pain, stiffness, and reduced mobility. The degradation products can also trigger further inflammation, creating a cycle of damage. A similar process involving MMP13 occurs in rheumatoid arthritis, where chronic inflammation drives cartilage breakdown.
The Connection Between MMP13 and Cancer
MMP13’s role in cancer centers on its ability to remodel the environment surrounding cells. Tissues are held together by a network of proteins called the extracellular matrix (ECM), which acts as a physical scaffold and barrier.
Some cancer cells exploit MMP13 to aid their growth and spread. Tumors can produce high levels of this enzyme to degrade the surrounding ECM. Breaking down this barrier carves a path for the primary tumor to expand and invade adjacent healthy tissues.
This enzyme’s activity is also connected to metastasis, the spread of cancer to distant parts of the body. By degrading the ECM, MMP13 helps cancer cells penetrate blood or lymphatic vessel walls. Once inside these systems, cancer cells can travel to other organs and establish new tumors.
Targeting MMP13 for Treatment
The involvement of MMP13 in diseases like arthritis and cancer makes it a target for drug development. The therapeutic strategy involves creating molecules, known as MMP13 inhibitors, to block the enzyme’s destructive activity. The main challenge is achieving selectivity, as the body produces over 20 different MMP enzymes, many with beneficial functions.
Early attempts to develop MMP inhibitors in the 1990s were unsuccessful because the drugs were “broad-spectrum,” blocking a wide range of MMPs instead of just MMP13. This lack of specificity led to significant side effects, including musculoskeletal syndrome characterized by joint pain and inflammation. These side effects occurred because the drugs interfered with the normal tissue remodeling functions of other MMPs.
Current research focuses on designing highly selective inhibitors. The goal is to develop a drug that targets only MMP13, leaving other beneficial MMP enzymes to perform their normal functions. This precise approach is intended to maximize therapeutic benefit while minimizing the risk of adverse side effects.