What is Cathepsin K?

Cathepsin K (CTSK) is a protein that is a type of protease, an enzyme that breaks down other proteins. It is also a member of the family of cathepsins. This particular cathepsin plays a role in breaking down the bone matrix as part of bone reabsorption and metabolism. The balance of bone breakdown and rebuilding can go awry, leading to osteoporosis. Cathepsin K inhibitors are being investigated as potential drugs to block this process and treat conditions such as osteoporosis.

Proteases are a large group of proteins that are divided into a variety of classes based on their substrates and the structure of their active site. CTSK is called a cysteine protease because it has the amino acid cysteine in its active site. Many proteases are produced in a larger inactive form known as a zymogen, and they do not damage surrounding tissue. The cathepsin family of proteases is produced in this form, and cathepsin K cleaves itself under acidic conditions, producing a smaller, active enzyme.

Most members of this protease family are found in lysosomes. These are cellular compartments that are highly acidic and full of enzymes that degrade cellular components. Cathepsin K was originally found in such compartments. The low pH of the lysosomes stimulates the enzyme to activate itself. CTSK can also be found extracellularly in the acidic environment where bone tissue is undergoing metabolism.

The bone matrix undergoes a constant process of being broken down by specialized cells known as osteoclasts and then is rebuilt by other types of cells. This process is generally in equilibrium, and the bones retain their strength. As women age, particularly after menopause, bone mass is frequently lost due to an excess of cathepsin K activity. This can result in the disease known as osteoporosis, in which bones are brittle and fracture easily. The disorder can be serious, and this tendency to fracture results in loss of mobility and sometimes early death.

There are currently drugs known as bisphosphonates used to treat osteoporosis. They can have serious side effects, and clinicians have been searching for alternative drugs. Cathepsin K inhibitors have been logical choices to target because of their role in blocking the breakdown of bone components.

The cathepsin K inhibitor odanacatib has proved promising in clinical trials in the United States, and is being developed by the pharmaceutical company Merck. This drug has passed the clinical trials for safety and and has shown promise in increasing bone density in postmenopausal women. Approval of this drug for use in the United States is contingent upon clinical testing showing that the drug is successful at ameliorating the symptoms of osteoporosis, such as increasing bone mass and limiting fractures.