What Has Eight Legs, But Can Maintain Two More?
January 27, 2015
If spiders gross you out, this may be a little creepy. The answer to the riddle is everyone’s favorite large hairy spider, the tarantula, but that’s not the whole story. Those two legs the tarantulas can maintain are human legs. Our legs.
This is according to new research from Duke University orthopedist Farshid Guilak who found a specific protein in tarantula venom can actually prevent human cartilage cells from dying off after severe injury. Guilak and his colleagues published their research in Proceedings of the National Academy of Sciences.
Cartilage cells – also called chondrocytes – are important for the human body’s ability to get around. They are present in the most highly mobile joints in the human body (elbow, knee, wrist, fingers, hips, etc.) and are responsible for maintaining the fluids that keep those joints running smoothly.
The trouble with the cartilage in these joints – called articular cartilage – is that they are not connected to the bloodstream in any way. So when cartilage is damaged, as athletes and people with osteoarthritis will tell you, it repairs slowly, if it repairs at all. Therefore, preserving articular cartilage is important for maintaining mobility throughout life.
Articular cartilage responds like most moving systems. When you use it for a while, it starts to wear down. It is sort of similar to motor oil. After some hard work lubricating an engine, motor oil will pick up dirt and sludge and will need replacement. Stretching and compressing cartilage will slowly wear it down. Luckily, as Guilak found in a previous study, routine movement activates a protein that changes the oil for us by making new cartilage cells.
Our bodies respond well to routine, low-stress damage to our cartilage, but in this study Guilak wanted to study what happens when the cartilage gets pummeled. Falls and other physical accidents can put huge stress on our joints and quickly kill off large numbers of cartilage cells. Other habits, such as running or chopping wood, also stress the joints, and though they don’t damage cartilage as seriously as a fall might, they can chip away at our joints more quickly than we can regrow cartilage cells.
Guilak and his colleagues wanted to determine what caused this damage on a molecular level, so they stressed cartilage cells with a special type of microscope that essentially pokes the subject with a tiny probe, and watched what the cells did.
They found that two proteins involved in movement detection throughout the body, Piezo1 and Piezo2, would both activate under stress and kill the cartilage cell. Further, Piezo1 and Piezo2 only activated under very high stress, explaining why falling off a ladder is far worse for your cartilage than walking to the kitchen for a banana. The impact from the fall is much greater, and therefore can activate more Piezo1 and Piezo2.
Here is where the tarantulas come in. Guilak and his colleagues naturally wanted to see if blocking Piezo1 and Piezo2 could slow down the cell death. One of the researchers, Frederick Sachs, found a few years ago that a small molecule in tarantula venom, called GsMTx4, effectively shuts down Piezo1.
Thankfully, the researchers were able to make GsMTx4 in the lab and tarantula bites will not become the new method to protect cartilage. They found their synthetic GsMTx4 blocked both channels and prevented cells in a petri dish from dying after compressing them.
Guilak and his colleagues are currently undertaking more projects to learn exactly how Piezo1 and Piezo2 work in cartilage cells, and how they might be harnessed for treating osteoarthritis and other cartilage-related conditions.
Some problems they might face are whether GsMTx4 will help cartilage after a major injury, as this study covers its use as a preventative measure. Also, the Piezo channels are found throughout the body, so before GsMTx4 could potentially be used to treat cartilage damage, researchers would need to determine what effects GsMTx4 has on the rest of the body. After all, GsMTx4 may not be the main culprit, but tarantulas include it in their venom for a reason.
But even if GsMTx4 does not end up rebuilding our joints and tarantulas are not secretly providing the key to pain relief, identifying the role of the Piezo channels in cartilage provides a concrete direction for future research that could help the millions of people who deal with osteoarthritis.
— Daniel Lane
Daniel Lane covers science, engineering, medicine and the environment in North Carolina.
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