Exercise has been touted to build bone mass, but exactly how this is actually achieved is a matter of debate. Now researchers show that an effort-induced hormone activates cells that are essential for bone remodeling in mice.
A research that appears in the journal Cell December 13 identifies a receptor for irisin, an exercise hormone, and shows that irisin affects sclerostin in mice, an important cellular regulator of bone structure in humans. The work can inform future treatments for osteoporosis, causing more than 8.9 million fractures worldwide annually.
"These results are potential game-changers in the areas of metabolism, muscle biology and physical activity," says co-author Bruce Spiegelman, cancer biologist at the Dana-Farber Cancer Institute in Boston. "We show that irisin works directly on osteocytes, the most common cell type in bone," says Spiegelman.
Irisine, secreted by skeletal muscle in response to endurance in mice and humans, has been associated with bone strengthening, calorie burning and improved cognition. But existence itself was once controversial and the mechanism underlying its effect on bone proved elusive.
Mammalian skeletons undergo continuous renovation. Old or damaged bone is replaced by new cells, a process that often starts with the death or breakdown of existing bone cells. Exercise – and irisine – both activate the protein sclerostin, a bone breakdown factor that is secreted by osteocytes in response to mechanical stress applied to the skeleton.
"Intermittent breakdown of bone seems to be interpreted as a signal to renew and build bones", says Spiegelman. "Proof of concept for this already exists, in the sense that the treatment with osteoporosis parathyroid hormone (PTH) is also a bone breakdown factor."
Small doses of irisin have been shown to improve bone density and bone strength in mice. To further investigate the role of irisin, researchers injected mice with irisine for six days. The injections increased sclerostin levels in their blood and increased their bone mass. In addition, mice that were genetically engineered to develop lack of irisin did not develop osteoporosis.
The next steps, says Spiegelman, will focus on optimizing different versions of irisin and antibodies against irisin "so that we can manipulate its effects through protein therapeutics." We also examine the effects on fat and in the nervous system. "
Identifying the molecular receptor for irisin, he says, is an important step towards finding new cells and tissues that respond to this hormone.
Material delivered by Cell Press. Note: content can be edited for style and length.