Tears in tiny bone cells called osteocytes appear an important step to better bones

August 29, 2017
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. Pictured are Drs. Meghan E. McGee-Lawrence and Paul McNeil. Credit: Phil Jones, Senior Photographer, Augusta University

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 report 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," says Dr. Meghan E. McGee-Lawrence, biomedical engineer in the Department of Cellular Biology and Anatomy at the Medical College of Georgia at Augusta University.

Osteocytes manage the osteoblasts that make bone as well as the osteoclasts that break bone down and were known to sense mechanical loading, but just how they sensed load was unknown.

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," says 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 . 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 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 says.

Conversely, the lack of loading and subsequent tearing may be why astronauts' bone and muscle weaken in zero gravity, McNeil says.

McGee-Lawrence is principal investigator on a new $450,000 National Science Foundation grant that will help them further parse this important puzzle and the potential for enabling better bone health with age and disease.

"We are wondering if with aging is due to osteocytes becoming more fragile or less able to repair as we age," say McNeil, co-investigator on the ongoing studies. "If they do, you would lose them over time and, in fact, we know you do lose them."

Part of what they 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.

"It's a way you can influence membrane repair rates so if we speed up how fast that tear repairs, is that going to influence the osteocytes?" McGee-Lawrence says. They'll also look at the impact of slowing repair down.

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

"We are starting to understand why calcium signaling gets initiated in wounded cells and then that gives us a mechanism we can target to try to influence how well bone detects mechanical loading," McGee-Lawrence says.

Disease may also complicate the common action of cell membrane tear and repair. For example, McNeil has shown diabetes, which is associated with bone loss, can lead to problems with membrane repair of other . Now the MCG scientists are looking at whether it similarly affects osteocytes.

Bone and muscle health are inextricably connected and McNeil has done pioneering work that shows one way we keep our muscles strong and even increase their size is through this process of tear and repair in the membrane of muscle cells.

"If you go to the gym and exercise your muscles, they are going to get bigger and stronger and at the same time if you sit around all day your muscles are going to get weaker," McGee-Lawrence says. "Bone does the same thing." McNeil notes the difference between the right and left hands and arms of a right-handed tennis player.

"This bone is full of . Some are building new bone, some are breaking down bone and it is constantly being remodeled," McNeil adds, holding up a large muskox bone.

People hit their peak bone mass in the late 20s or early 30s. After that, the percentage of osteoblasts to osteoclasts starts to shift so that you are slowly losing rather than building bones. Active youth, they note, tend to build a better bone mass that should comfortably see them into old age, particularly if they remain active.

Failure of rapid membrane repair is associated with weaker muscles even muscle disease, they note, and the scientists expect the same also holds true in . Future studies include exploring whether repair failure contributes to common problems like osteoporosis.

Explore further: Research identifies how master regulator, bone-building protein can be used for therapy

Related Stories

Research identifies how master regulator, bone-building protein can be used for therapy

June 21, 2017
The WNT1 ligand has previously been identified in bone disease, but its role in bone homeostasis, its cellular source and targets in bone have only just recently been identified. The research, led by Dr. Brendan Lee at Baylor ...

Estrogen regulates pathological changes of bones via bone lining cells

July 28, 2017
The female sex hormone estrogen plays an important role in the structural stability of bones. To date, however, it had been unclear exactly which cells were involved in the hormone's protective function in preventing changes ...

Study offers new hope for treatment of osteoporosis

March 22, 2016
An international study by The University of Western Australia may lead to a new treatment for osteoporosis caused by age-related bone loss in elderly women.

It's never too soon to safeguard your bones

August 9, 2017
(HealthDay)—Bone health is literally something you build on throughout your life, not just as a child. And the efforts you put in now will keep bones strong and help prevent the bone-thinning disease osteoporosis later ...

Osteoporosis drugs appear to impede cell membrane repair

April 14, 2014
A class of drugs widely used to treat osteoporosis appears to impede a cell's ability to repair a protective outer membrane that helps determine what enters and exits, researchers report.

Recommended for you

Researchers develop treatment to reduce rate of cleft palate relapse complication

September 22, 2017
Young people with cleft palate may one day face fewer painful surgeries and spend less time undergoing uncomfortable orthodontic treatments thanks to a new therapy developed by researchers from the UCLA School of Dentistry. ...

Exosomes are the missing link to insulin resistance in diabetes

September 21, 2017
Chronic tissue inflammation resulting from obesity is an underlying cause of insulin resistance and type 2 diabetes. But the mechanism by which this occurs has remained cloaked, until now.

Thousands of new microbial communities identified in human body

September 20, 2017
A new study of the human microbiome—the trillions of microbial organisms that live on and within our bodies—has analyzed thousands of new measurements of microbial communities from the gut, skin, mouth, and vaginal microbiome, ...

Study finds immune system is critical to regeneration

September 20, 2017
The answer to regenerative medicine's most compelling question—why some organisms can regenerate major body parts such as hearts and limbs while others, such as humans, cannot—may lie with the body's innate immune system, ...

Immune cells produce wound healing factor, could lead to new IBD treatment

September 20, 2017
Specific immune cells have the ability to produce a healing factor that can promote wound repair in the intestine, a finding that could lead to new, potential therapeutic treatments for inflammatory bowel disease (IBD), according ...

As men's weight rises, sperm health may fall

September 20, 2017
(HealthDay)—A widening waistline may make for shrinking numbers of sperm, new research suggests.

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.