Irisin is a hormone-like myokine secreted from skeletal muscle in response to exercise Considering that an intimate relationship between skeletal muscle and bone has been well established and that physical exercise physiologically stimulates the skeleton strengthening, we explored a possible involvement of Irisin on bone metabolism.
Our findings demonstrated that the myokine Irisin improves cortical bone mass and geometry in vivo, supporting the idea that Irisin recapitulates some of the most important benefits of physical exercise on the skeleton and plays protective role on bone health. Healthy young male mice, treated with a micro-dose of recombinant Irisin (r-Irisin), showed increased cortical bone mineral density (cBMD), bending strength and energy to fracture. Although Irisin clearly recapitulates some of the most important benefits of loading activity, such as physical exercise, its efficacy on unloading-induced bone loss was still unknown. To this end, we took advantage of the hind-limb suspended mouse, a murine model widely accepted for simulating weightlessness. Our data show that r-Irisin treatment has a striking effect on both cortical and trabecular bone loss. As expected, unloaded mice treated with vehicle displayed a remarkable decrease of cortical and trabecular bone mineral density (BMD), whereas in Irisin-treated unloaded mice no loss of BMD was observed with respect to control mice kept in resting condition. Likewise, by treating mice after they already developed disuse-induced bone loss, r-Irisin was able to restore the damaged mineral component. Moreover, we demonstrated that r-Irisin treatment markedly protects muscle mass, known to be suffering from atrophy during unloading. Our data revealed for the first time that r-Irisin treatment prevents and retrieves disuse‐induced bone loss and muscle atrophy. These findings may lead to develop an Irisin-based therapy for the prevention and treatment of osteoporosis and sarcopenia in all patients who cannot perform physical activity, as occurs during aging and immobility, and it could also represent a countermeasure for astronauts exposed to microgravity during space flight missions.