Irisin, a myokine produced from muscle in response to physical activity, has recently been suggested to play a role in muscle-bone communication. Systemic administration of irisin in mice increased bone formation, cortical bone mass and bone strength. In vitro, irisin induced the differentiation of bone marrow stromal cells into mature osteoblasts. However, irisin’s effects on mature osteoblasts and osteoclasts are unknown. Therefore, this study aimed to investigate the direct effects of irisin on bone cells.  

The effect of irisin on primary rat osteoblast proliferation was assessed by ³H-thymidine incorporation following 24 hour treatment with 25, 50 and 100 ug/mL irisin. Differentiation was studied in osteoblasts cultured for 21 days in the presence of irisin, using Von Kossa staining to visualise the mineralised area. Osteoclastogenesis was determined by counting multinucleated TRAP+ve cells in mouse bone marrow cultures following treatment on day 2 and 4 and fixation on day 7.

Irisin had no effect on mature rat osteoblast proliferation and the formation of mineralised matrix by differentiated osteoblasts. The numbers of multinucleated TRAP+ve cells were similar in control bone marrow cultures and in cultures treated with irisin. Thus, irisin does not appear to have a direct effect on the proliferation and differentiation of mature osteoblasts, nor the formation of osteoclasts in mouse bone marrow cultures. Further experiments will be conducted to evaluate if irisin has an effect on osteocytes.

Our results suggest that the anabolic effect of irisin in bone seen in vivo might primarily be from enhancing early stages of osteoblast differentiation from bone marrow stromal cells and possibly through indirect mechanism of action, as irisin is also known to play a role in energy metabolism through fat cell regulation. Therefore we will also evaluate the mechanisms controlling the switch from bone marrow stromal cells into osteoblasts and adipocytes.