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Programmed Death of Tendon Cells May Explain Tendinopathy

In 1998, researchers received the Nobel Prize in medicine for their discovery of a molecule called nitric oxide. This molecule is made up of one nitrogen (N) and one oxygen (O) atom. It is present in all mammals, including humans. It is NOT the same as nitrous oxide (N2O), the laughing gas used by dentists.

Nitric oxide does many, many things in the body. For example, it acts like teflon in the blood vessels. It keeps the blood moving smoothly and prevents plaque build-up that causes atherosclerosis. It helps with long-term memory, sexual function, nerve transmission, and boosts the immune system function. Scientists have since discovered that it also plays a role in wound healing for fractures and tendon damage.

Now in a startling turn around, researchers from England have discovered nitric oxide may have a negative part to play in the development of tendinopathy. Their focus was on the Achilles tendon of the foot. The Achilles is at the end of the gastrocnemius (calf) muscle and inserts or attaches into the calcaneus (heel) bone of the foot. Tendinopathy refers to a degenerative process in the tissues without inflammation.

As it turns out, nitric oxide causes apoptosis or cell death. This is a programmed or predetermined cell death. That's all part of the natural body function that gets rid of old cells to make way for new, healthier cells.

When apoptosis occurs, the dying cell doesn't dump any of its contents, which is what would happen if there was damage to tendon cells from trauma as a result of injury or overuse. It's those released enzymes in injured cells that signal inflammation and a repair sequence.In the case of apoptosis, the old cell orchestrates its own death without release of its contents.

Now how does all this fit with Achilles tendon problems? Well, with trauma and especially overuse injuries, the body releases more nitric oxide than usual. While a certain amount of nitric oxide is good, like anything else, too much of a good thing (i.e., nitric oxide) can go south. Overproduction of nitric oxide becomes toxic to the tendon tissue and sets up excessive apoptosis.

The result? Achilles tendinopathy. The incidence of these injuries in more and more adults is suggested to be the result of more people engaging in sports and recreational activities. But biomechanical factors and training errors also contribute to the problem.

And to add to the data collected, it appears that nitric oxide-induced apoptosis leading to achilles tendinopathy affects more than just the aging or overzealous athlete -- it seems that folks with diabetes, hypertension, or obesity are also at risk for tendinopathy.

Just exactly what is the effect of nitric oxide on the tendon tissue? To find out, scientists studied samples of tissue taken from 14 patients with Achilles tendinopathy. They compared these samples with tissue collected from normal, healthy Achilles tendons in the same patients.

The samples were sent to the lab where they were examined and analyzed. Three separate types of cells were measured. These included caspase-3 cells, TUNEL cells, and inducible nitric oxide synthase (iNOS) -- all three cell types are released at the time of cell death (apoptosis).

They found a significant increase in all three cell types in the tendon with tendinopathy. These results suggest that a larger number of cells in the diseased tendon were undergoing apoptosis. The natural conclusion is that apoptosis is a part of the reason why Achilles tendinopathy occurs.

Since many studies have proven there are no inflammatory cells present in chronically painful tendons, there must be some other mechanism to explain what's going on. That's where this idea that nitric oxide-induced apoptosis may be the pathway by which tendinopathies develop.

If scientists can solve the mystery of what's happening at the cellular level, then it might be possible to find faster and more effective ways to treat tendon problems. Other studies have shown excessive apoptosis in tendons just before they ruptured, so maybe there will even be a way to prevent tendon injuries with this new knowledge.

There still remain many unanswered questions and conflicting information about nitric oxide, how it works, and what effects it has on tissues. For now, the results of this study add a bit more information. Too much nitric oxide from high-strain mechanical loading on a tendon may be harmful to the tendon healing process.

The authors conclude that the release of excess nitric oxide might be the reason tendinopathy occurs when there's no obvious inflammation. Hopefully, future studies will continue to unravel and solve the complete mystery so we can get on with the business of finding ways to prevent (or treat) tendon problems.


Christopher J. Pearce, FRCS(Tr&Orth), MFSEM(UK), et al. Is Apoptosis the Cause of Noninsertional Achilles Tendinopathy? In The American Journal of Sports Medicine. December 2009. Vol. 37. No. 12. Pp. 2440-2444.

12/10/2009

*Disclaimer:* The information contained herein is compiled from a variety of sources. It may not be complete or timely. It does not cover all diseases, physical conditions, ailments or treatments. The information should NOT be used in place of visit with your healthcare provider, nor should you disregard the advice of your health care provider because of any information you read in this topic.
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