Irisin Linked to Mechanisms for Bone Metabolism
Two weeks of voluntary wheel running induces higher expression of irisin, a fat-burning hormone that is released during exercise, in bone tissue in mice. In addition, systemic administration of irisin increased bone formation and thickness, mimicking the effects of exercise on the mouse skeletal system. The findings demonstrate a potential new mechanism for the regulation of bone metabolism. The study was led by scientists from Tufts University School of Dental Medicine (TUSDM) and published in Bone Research.
“Our results provide insight into the complex regulatory interplay of muscle, bone and fat tissues. Increased irisin levels in circulation upon systemic administration can recapitulate part of the beneficial effects of exercise in the skeletal system,” said senior study author Jake Chen, D.M.D., M.D.S., Ph.D., professor and biological sciences researcher at TUSDM. “Further experimentation will be needed to evaluate the involvement of irisin and other factors increased by exercise and expressed by bone, muscle and fat tissue.”
Previous studies have revealed that exercise induces the production of irisin and its precursor molecule, FNDC5 (fibronectin-type III domain-containing 5) protein, which convert white fat tissue into beneficial, calorie-burning brown fat. Irisin has been linked to improved glucose tolerance and weight loss in obese, prediabetic mice. While most studies have focused on irisin produced by muscle tissue, some research has suggested that irisin increases bone mass in addition to its metabolic benefits. However, it was unknown whether irisin is secreted by bone upon exercise or whether it regulates bone metabolism.
To investigate, Chen and his colleagues tested a group of five-week-old mice, with two weeks of voluntary wheel running. Compared to a control group without access to a running wheel, mice that had exercised expressed six-fold higher FNDC5 and irisin expression in bone tissue. Irisin expression was observed in several different bone regions, including the growth plate, trabecular bone, cortical bone, articular cartilage and muscle–bone interface.
When mice were injected with irisin or viruses engineered to express irisin, the team found significant increases in bone volume and thickness compared to mice treated with saline. The team evaluated the effects of recombinant irisin in bone cell lines, and found that irisin can directly increase the production of osteoblasts—cells that synthesize bone—and mineralization, while inhibiting the production of osteoclasts—cells that break down bone.
The team’s findings demonstrate that irisin produced by bone could have a role in bone metabolism through both direct mechanisms and indirect mechanisms, as the transition from white fat to brown fat has been shown to lead to increased bone formation by previous studies. In addition, recombinant irisin has also been shown to suppress sclerostin, a protein that is involved in bone loss during prolonged lack of mechanical load, such as in bed-ridden patients.
“Exercise-induced irisin may not only act as an endocrine factor capable of promoting the browning of white adipose tissue, but could also regulate bone metabolism by autocrine mechanisms,” said Chen, who also serves as faculty in the Cell, Molecular & Developmental Biology program at the Sackler School of Graduate Biomedical Sciences at Tufts. “Our results suggest that irisin may have a therapeutic potential in strengthening bone in bone-loss-associated diseases, and additional studies are needed to evaluate the underlying mechanisms by which irisin functions.”
Zhang, J., Valverde, P., Zhu, X., Murray, D., Wu, Y., Yu, L., … Chen, J. (2017). Exercise-induced irisin in bone and systemic irisin administration reveal new regulatory mechanisms of bone metabolism. Bone Research, 5, 16056. doi:10.1038/boneres.2016.56
This article has been republished from materials provided by Tufts University. Note: material may have been edited for length and content. For further information, please contact the cited source.
3-D Printed Sugar Scaffolds Offer Sweet Solution for Tissue EngineeringNews
University of Illinois engineers built a 3-D printer that offers a sweet solution to making detailed structures that commercial 3-D printers can’t: Rather than a layer-upon-layer solid shell, it produces a delicate network of thin ribbons of hardened isomalt, the type of sugar alcohol used to make throat lozenges.READ MORE
Schizophrenics' Blood Contains RNA From More MicrobesNews
The blood of schizophrenia patients features genetic material from more types of microorganisms than that of people without the debilitating mental illness, research at Oregon State University has found. What’s not known is whether that’s a cause or effect of the severe, chronic condition that strikes about one person in 100.READ MORE
Comments | 0 ADD COMMENT
2nd Annual Artificial Intelligence in Drug Development Congress
Sep 20 - Sep 21, 2018