It has been recently reported that, after physical exercise activity, the skeletal muscle releases Irisin, the newly identified myokine able of driving transition of white adipocytes to brown, following a phenomenon known as the browning response. This result has suggested that skeletal muscle is crucial in the regulation of energy homeostasis, supporting the idea that it can be considered an endocrine organ that targets adipose tissue by promoting energy expenditure. In accordance with these new findings, we hypothesized that a direct involvement of Irisin in bone metabolism could also exist, demonstrating its ability to enhance differentiation of bone marrow stromal cells into mature osteoblasts (OBs) by increasing the expression of alkaline phosphatase and collagen I.
In view of further proving the involvement of Irisin in bone metabolism, we validate its direct effect on OBs by using recombinant Irisin (r-Irisin). Phosphorylation of MAPK ERK and expression of Atf 4 (P<0.001), the key trascription factor of OB differentiation, were significantly increased after Irisin treatment. Furthermore, ALP and pro-collagen I mRNA resulted up regulated (P<0.001), as we already demonstrated by treating OBs with conditioned medium from primary myoblasts of exercised mice.
To recapitulate in vivo the effect of physical exercise, with regard to the specific action of the myokine Irisin on the skeleton, we injected mice with r-Irisin. Here we show that BV/TV of Irisin-treated mice was higher than vehicle-injected mice and this positive effect on bone was also confirmed by reduction of RANK-L serum concentration in treated mice that, given the unchanged OPG levels, resulted in a decreased RANK-L:OPG ratio.
These data demonstrate for the first time that Irisin could be a new anabolic molecule to the bone and add new evidence to the positive effect on skeletal homeostasis exerted by physical exercise, highlighting a novel link in the bonemuscle axis.
17 May 2014 - 20 May 2014