Identify the mechanism by which exercise strengthens bones


Scientists at the Research Institute at the University of Texas Southwestern Children’s Medical Center (CRI) have identified the specialized environment, known as a niche, in the bone marrow where new bone and immune cells are produced. The study, published in the journal ‘Nature’, also shows that stimulation induced by movement is necessary for the maintenance of this niche, as well as the bone and immunity-forming cells it contains. Together, these findings identify a new way that exercise strengthens bones and immune function.

Researchers in Professor Morrison’s Laboratory found that forces created by walking or running are transmitted from bone surfaces along arteriolar blood vessels to the marrow within bones. The bone-forming cells that line the exterior of the arterioles sense these forces and are induced to proliferate.

Not only does this allow the formation of new bone cells, which helps thicken the bones, but the bone-forming cells also secrete a growth factor that increases the frequency of the cells that form lymphocytes around the arterioles. Lymphocytes are the B and T cells that allow the immune system to fight infection.

When the ability of bone-forming cells to sense the pressure caused by movement, also known as mechanical forces, was inactivated, the formation of new bone cells and lymphocytes was reduced, causing the bones to become thinner and reduce the ability of mice to clear a bacterial infection.

“As we age, the environment of our bone marrow changes and the cells responsible for maintaining skeletal bone mass and immune function are depleted. We know very little about how this environment changes or why these cells decline with age.” Sean Morrison, director of the CRI and investigator at the Howard Hughes Medical Institute – Previous research has shown that exercise can improve bone strength and immune function, and our study uncovered a new mechanism by which this occurs. “

Previous work from Morrison’s lab discovered skeletal stem cells that give rise to most of the new bone cells that form during adulthood in the bone marrow. They are leptin receptor + (LepR +) cells. They form the exterior of blood vessels in the bone marrow and form growth factors critical to the maintenance of blood-producing cells.

Morrison’s lab also discovered that a subset of LepR + cells synthesize a previously undiscovered bone-forming growth factor called osteolectin. Osteolectin promotes the maintenance of the adult skeleton by causing LepR + to form new bone cells.

In the current study, Bo Shen, a postdoctoral fellow in Morrison’s lab, took a closer look at the subset of LepR + cells that produce osteolectin. He discovered that these cells reside exclusively around the arteriolar blood vessels in the bone marrow and that they maintain nearby lymphoid progenitors by synthesizing stem cell factor (SCF), a growth factor that these cells depend on. Removal of SCF from osteolectin-positive cells depleted lymphoid progenitors and undermined the ability of mice to mount an immune response to bacterial infection.

“Along with our previous work, the findings of this study show that osteolectin-positive cells create a specialized niche for lymphoid and bone-forming progenitors around the arterioles,” Shen said. Osteolectin-positive cells could increase bone formation and immune responses, especially in the elderly. “

Shen found that the number of lymphoid progenitor cells and osteolectin-positive cells decreased with age. Curious if he could reverse this trend, he put wheels on the cages so the mice could exercise. He found that the bones of these mice became stronger with exercise, while the number of osteolectin-positive cells and lymphoid progenitors around the arterioles increased. This was the first indication that mechanical stimulation regulates a niche in the bone marrow.

He discovered that cells positive for osteolectin expressed a receptor on their surfaces, known as Piezo1, that sends signals within the cell in response to mechanical forces. When Piezo1 was removed from cells of osteolectin-positive mice, these cells and the lymphoid progenitors they support were depleted, weakening bones and altering immune responses.

“We believe we have found an important mechanism by which exercise promotes immunity and strengthens bones, in addition to other mechanisms previously identified by others,” Morrison notes.

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