Researchers discover gene that controls bone-to-fat ratio in bone marrow

July 12, 2018, University of California, Los Angeles
Credit: CC0 Public Domain

In an unexpected discovery, UCLA researchers have found that a gene previously known to control human metabolism also controls the equilibrium of bone and fat in bone marrow as well as how an adult stem cell expresses its final cell type. The findings could lead to a better understanding of the disruption of bone-to-fat ratio in bone marrow as well as its health consequences, and also point to the gene as a promising therapeutic target in the treatment of osteoporosis and skeletal aging.

Until now, the PGC-1α gene, a gene activator, was primarily known to regulate reactions that convert and sustain energy for human cells. The study—led by Dr. Cun-Yu Wang, chair and professor of oral biology and medicine, and Dr. Bo Yu, assistant professor of restorative dentistry, both from the UCLA School of Dentistry—has shown that PGC-1α may actually impact whether stem cells turn into fat cells or cells and in turn control the -to-fat balance in bone marrow.

The research is published online in the journal Cell Stem Cell.

Bone marrow tissue is composed of blood cells, marrow adipose tissue (or fat) and supportive stromal cells (connective tissue cells of any organ). For years, clinicians have noted an inverse relationship between and fat cells in bone marrow in various medical conditions. An increase in marrow fat is often accompanied by a decrease in bone mass in aging as well as osteoporosis and other metabolic disorders.

Osteoblasts, or bone-forming cells, and adipocytes, or fat-forming cells, derive from a common pool of , which are stromal cells that can become several different types of cells. This composition suggests a tradeoff between the two cell types and an abnormality in how a cell expresses its final type of mesenchymal stem cell in skeletal aging and osteoporosis. The molecular basis of this phenomenon is poorly understood. Further study of and insights into the inverse relationship of bone loss to fat formation may lead to new treatments for these conditions.

Wang and Yu noticed in both human and mouse bone marrow that the expression of the PGC-1α gene decreased dramatically with advanced age. The researchers initially wanted to better understand the role of this gene in age-induced bone loss. The pair began their study by creating a mouse model that had the PGC-1α proteins removed from mesenchymal stem cells. They found something unexpected when these mice underwent a procedure that simulated osteoporosis—there was a significant increase in marrow fat along with the expected decrease in bone mass.

"What we found was particularly intriguing, given that PGC-1α has previously only been linked with metabolism but not with adult stem cells," said Wang, who is also the dental school's associate dean for graduate studies. "This revelation suggests that PGC-1α could influence how stem cells differentiate into bone and not fat cells, and it could also lead to new therapeutics in osteoporosis."

To test their findings, they created a mouse model in which the PGC-1α gene expression was increased. What occurred was the opposite of what happened with their first model—there was a slowdown in and a decrease in bone marrow fat, which suggests that PGC-1α may play a protective role in maintaining the bone-to-fat balance.

The team found that PGC-1α directly activated the expression of TAZ, a master regulator previously reported to promote bone formation while inhibiting fat cell differentiation of mesenchymal stem .

"You could compare PGC-1α to a river that nourishes or maintains bone mass as it winds through the marrow landscape," Yu said. "The river runs dry as we age, prompting more to form at the expense of bone."

Physical exercise has been found to induce PGC-1α expression. This study also suggests that regular physical exercise might help to maintain bone health and prevent skeletal aging, as well as provide other health benefits.

Explore further: Researchers engineer human bone marrow tissue

Related Stories

Researchers engineer human bone marrow tissue

June 5, 2018
Researchers have developed an artificial tissue in which human blood stem cells remain functional for a prolonged period of time. Scientists from the University of Basel, University Hospital Basel, and ETH Zurich have reported ...

How bone marrow niches keep stem cells thriving

April 19, 2018
Hematopoietic stem cells (HSCs) are a class of stem cells located in bone marrow. HSCs give rise to every type of blood cell—from the red blood cells that carry oxygen to the white blood cells of the immune system. Bone ...

Weight loss surgery's effects on bone marrow fat and bone mass

August 9, 2017
Bone marrow fat is thought to regulate bone metabolism, and high levels of marrow fat are seen in states of low bone mass, severe underweight, and diabetes. In a study of obese women undergoing gastric bypass surgery, increases ...

Researchers describe mechanism that underlies age-associated bone loss

September 22, 2017
A major health problem in older people is age-associated osteoporosis—the thinning of bone and the loss of bone density that increases the risk of fractures. Often this is accompanied by an increase in fat cells in the ...

Study shows adipose stem cells may be the cell of choice for therapeutic applications

February 24, 2017
An international team of researchers, funded by Morris Animal Foundation, has shown that adipose (fat) stem cells might be the preferred stem cell type for use in canine therapeutic applications, including orthopedic diseases ...

New finding on the formation of fat tissue in man

July 16, 2015
While all red and white blood cells derive from stem cells in the bone marrow, the scientific community has been divided over whether bone marrow cells are also able to produce other cell types. In the present study, the ...

Recommended for you

Enzyme identified as possible novel drug target for sickle cell disease, Thalassemia

July 19, 2018
Medical researchers have identified a key signaling protein that regulates hemoglobin production in red blood cells, offering a possible target for a future innovative drug to treat sickle cell disease (SCD). Experiments ...

Mice given metabolite succinate found to lose weight by turning up the heat

July 19, 2018
A team of researchers with members from institutions across the U.S. and Canada has found that giving the metabolite succinate to mice fed a high-fat diet prevented obesity. In their paper published in the journal Nature, ...

Supplement may ease the pain of sickle cell disease

July 19, 2018
(HealthDay)—An FDA-approved supplement reduces episodes of severe pain in people with sickle cell disease, a new clinical trial shows.

Analytical tool predicts genes that can cause disease by producing altered proteins

July 19, 2018
Predicting genes that can cause disease due to the production of truncated or altered proteins that take on a new or different function, rather than those that lose their function, is now possible thanks to an international ...

Childhood stress leaves lasting mark on genes

July 18, 2018
Kids who experience severe stress are more likely to develop a host of physical and mental health problems by the time they reach adulthood, including anxiety, depression and mood disorders. But how does early life stress ...

Scientists uncover DNA 'shield' with crucial roles in normal cell division

July 18, 2018
Scientists have made a major discovery about how cells repair broken strands of DNA that could have huge implications for the treatment of cancer.

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.