Extended time in space weakens the bones of astronauts, so scientists are working to better understand how bones sense and deal with the normal forces exerted on them by the purpose of their bones. to keep strong.
The ability of the skeleton to adapt to mechanical loading – the forces exerted on both bone by gravity and muscle in response to movement – is critical to bone health, and conditions such as spaceflight or spinal injuries can hinder added, says Dr. Meghan E. McGee-Lawrence, a biochemical engineer in the Department of Cellular Biology and Anatomy at Georgia College of Medicine.
“It’s been a problem for the astronauts on the International Space Station for a long time, and it’s going to be a problem for the endeavor to send astronauts to Mars in the end,” he said. McGee-Lawrence says.It’s also a problem here on Earth after a spinal injury, a long bedtime and for an inactive population of any age.
McGee-Lawrence just received a $ 750,000 grant from NASA to help her better understand how lack of gravity and other causes of abuse affect normal skeletal dynamics, and ways to build healthy dynamics on it. back when normal options such as more physical activity and weight lifting are not workable.
“If we can find a way to make bone more sensitive to mechanical loading, we would be able to increase bone size with less effort. That is a long – term goal,” she says.
Its focus is the natural sensors of mechanical loading on the bone called osteocytes. They are the most common cell in the bone, and the McGee-Lawrence Laboratory was the first to report that tears, known as plasma membrane disorders, occur in osteocytes with mechanical loading, and, when all goes well, the result is healing of tears and bone building.
They have shown that plasma breakdown occurs in healthy osteocytes within a minute in response to loading and initiates immediate changes such as the release of more calcium, which in turn alters the feeling of molecules that regulate the activity of bone-forming osteoblasts and bone-loss osteoclasts.
Calcium found in abundance in the extracellular stream around osteocytes runs through the new opening where the mineral, best known for building strong bones and teeth, instead acts as a call for action for these cells.
When there are few tears and little mechanical loading, the message to osteoblasts is that there is no need for denser bone and the osteoclasts replace some of the bone matrix. On the other hand, when osteocytes feel a lot of loading and tearing, they instruct osteoblasts to go up bone density and osteoclasts to cut back on resorption.
Her lab has shown that just moving around in cages produces a few tears in the long bones of mice, which, like the ones in our legs, support our weight and ‘allow us to move. That baseline suggests that these tears are part of the normal response to a daily gravitational pull, she said, and one of the reasons astronauts struggle with bone loss in space.
So they look directly at what happens to the formation and repair of plasma membrane disorder in osteocytes in response to misuse. They are also looking for ways to normalize this essential process in maintaining healthy bone against abuse that occurs in space as well as on Earth.
“Our hope is to find out how misuse affects this membrane rupture mechanism and whether it contributes to the bone loss caused by malnutrition. abuse and, if so, can we do anything to reverse these processes, “she says.” Can we do something for the osteocytes to make them more likely to experience it? tears or more likely to repair those tears and then, accordingly, do so so that there is less bone loss in use. “
She and her colleagues have some evidence that no less tears are good and want to further explore what happens to the stage of repair with abuse. They also want to know what level of healing is best: Does slow repair increase osteocyte survival, or does survival improve with quick repair? It is certain that if the tears do not heal, osteocytes will not survive.
“The good news is that we can dial in all directions,” she says. But they say faster repairs don’t have to be better because they suspect that calcium levels are into a relationship to the cell’s response to tears.
“Think of a membrane rupture as a door into the cell. If you slam the door too fast, there is not enough time for the cell to feel it rupture and begin to respond to the signals,” she says.
Because they already have a good knowledge of the molecular mechanism that helps heal tears, they already have some genetic and pharmacological methods to alter both the propensity of osteocyte rupture and the extent to which tears occur. as soon as it repairs. She believes that proteins involved in tear repair of organs, such as PRKD1, which reside in the cell membrane and reach early to the site of tears, are logical targets for both .
“The ultimate goal is whether we can create a method, whether it is a drug therapy or a different type of regimen that will make these processes work better in astronauts and humans on earth that are also being abused. , “she says.
Despite side effects such as resistance training, astronauts are known to lose 1-1.5% of their bone mineral density in stressful places, such as bumps and knees, every month, she says, and the planned seven-month trip to Mars is likely to mean all astronauts develop osteopenia, a weakening of bone mass that usually occurs with age, and 80% will develop osteoporosis. “That’s a real problem. Not only are they actively losing bones while in space, at some point they have to come back to gravity … and then what will happen? ” she says. Studies suggest that it is a long road to getting over bones for astronauts despite being physically healthy when they leave.
So she and her research team are also debating what happens to tearing and repairing with resume use and how that links to bone strength in their animal model. Adhering to what astronauts are finding, they have evidence that while resuming exercise may help, osteocytes are less likely to repair tears and survive after a long period of use.
There are effective treatments, such as bisphosphonates, that help with age-related bone loss, but they have not been proven to be effective when misused as a major driver. “That’s why we need to create better, more effective targets, to try to prevent the loss of abused bone,” she says.
McGee-Lawrence has worked with retired MCG cell biologist Dr. Paul McNeil, an expert in plasma membrane repair, who has recorded calcium within a cell when tears occur in several cell types, including muscle cells. Tears and muscle cell membrane repair are crucial in how muscles grow in response to weight lifting.
While it has long been clear that mechanical loads also translate to stronger bones, just as remains a question, she says. Like the McNeil studies with muscle, she suspects plasma membrane tears are important.
“We believe the formation of these tears is important for how the bone cells know they are exposed to that level of loading,” she says, especially of high-impact loading that comes from running and jumping. ”Cells need a way to know what’s going on outside their cell membrane. Here is one way to do that. “
Each star-shaped osteocyte has 50 to 60 arm-like processes, resembling zero cell dendrites, which allow it to sense its surroundings, communicate with other osteocytes in addition to the osteoblasts and osteoclasts. Like many cell types, osteocyte numbers decline with age along with the ability of your bone to respond to the weight, or lack of load, put on.
Osteoporosis is called a silent disease because it usually has no symptoms until a bone fractures or vertebrae collapse, according to the National Osteoporosis and Allied Bone Diseases Resource Center of the National Institutes of Health. It affects all sexes and all racial and ethnic groups and can occur at any age, although risk increases with age. Inactivity and smoking also increase risk and some medications, such as corticosteroids, can too.
NASA has plans to put a woman and a man on the Moon for further study by 2024 and to establish a permanent human presence there within ten years. What NASA is learning from these extended space missions and from their rover explorations on Mars – a new rover called Perseverance today, Feb. 18 – will help better prepare for sending astronauts to Mars, the fourth planet from the sun.
Source:
Georgia Medical College at Augusta University