The force gravity and physical activity put on our bones causes tiny tears in the membranes of the tiny cells that enable us to make or break down bone, scientists say.

While that may sound bad, it’s actually a key piece of how the force we put on our bones helps keep them strong, they reported in the Journal of Orthopaedic Research.

“The bone has to constantly adapt and make sure that is has the right design to withstand the loads you are going to put it through,” said Dr. Meghan E. McGee-Lawrence, biomedical engineer in the Department of Cellular Biology and Anatomy at the Medical College of Georgia at Augusta University.

McGee-Lawrence and MCG cell biologist Dr. Paul McNeil are the first to find the small tears in response to force exacted by walking up the stairs or lifting weights.

Not only do the cells experience membrane tears but it’s the highest number McNeil, an expert in cell membrane repair, has seen in a variety of cell types. “It’s remarkable,” said the study coauthor. And, the heavier the mechanical load, the more tears; for example the mice walking on a treadmill versus just moving about in their cage.

Better understanding the specific mechanism by which these cells sense then respond to mechanical load should enable identification of logical targets for improving the strength and health of aging bones as well as bones challenged by diseases like diabetes, says McGee-Lawrence the study’s corresponding author.

Osteocytes are plentiful in bone and each has hundreds of tiny processes reaching out in every direction that help secure them to the bone matrix. McGee-Lawrence likens their look to a sweetgum ball. She and McNeil have early evidence the diminutive cells and their projections are both very vulnerable to tearing and that vulnerability appears to make them a natural for responding to mechanical load.

Once tears happen to cell membranes, more calcium rushes inside the cells. This mineral closely associated with bone health and present outside the cell at concentrations 10,000 times higher than inside the cell, was known to be an initiating signal, McNeil says. His work has shown how in many cell types including now osteocytes, the load causes the tears which allows calcium to rush in to both rapidly heal tears and to set in motion inside a host of actions that, in this case, remodels bone.

In cell cultures, they watched as increased calcium levels inside osteocytes triggered an increase in the production of the protein c-fos. The protein also is well-studied and known to be involved in the signaling pathways that lead to stronger bones in response to exercise, but c-fos’ connection with membrane tearing was another unknown.

Osteocytes use their micron-thin tentacles to communicate with each other and the scientists also learned that when one osteocyte gets tears, it appears to communicate its load to neighboring osteocytes so the calcium level goes up in those as well even without a tear. The message the torn osteocyte shares it to tell osteoblasts to make the bones stronger and the osteoclasts to quit breaking bone down.

The idea of further shoring up bone is likely to be better prepared for whatever mechanical load comes next, McGee-Lawrence said.

Part of what the researchers are doing with the new grant includes looking at mice with a genetic deficiency in cell membrane repair. They want to see if the 50-year-old drug poloxamer 188, which was designed to reduce the thickness of blood, is found in products like toothpaste and has been shown to repair other cell membranes, might help osteocytes remain proficient at responding to mechanical load. Like many of our senses that dull with age, aging osteocytes don’t sense critical mechanical loads as well.

No drug on the market for osteoporosis is known to enhance osteocyte sensitivity.