Relationship between muscle FNDC5, FGF21 mRNA, miR-150 and bone loss after sciatic denervation.

Abstract

It has been proposed that muscle influences adjacent bones, but the mechanisms by which muscle regulates bone physiology are not fully understood. Sciatic denervation is an experimental model that induces both skeletal muscle atrophy and osteoporosis. Therefore, the aim of this study was to analyze, in this animal model, expression of myokines in the atrophic soleus and its possible effect on changes in tibia microarchitectural parameters in 9-12 weeks old male rats. For this purpose, soleus insulin-like growth factor-1 (IGF-1), interleukin-6 (IL-6), fibronectin type III domain-containing 5 (FNDC5), fibroblast growth factor 21 (FGF21) mRNA, and miR-150, were measured by real-time PCR and tibia microarchitecture was assessed 3, 7, and 14 days after sciatic denervation. Denervation induced soleus atrophy and decreased trabecular bone density, thickness, and number. In the atrophic soleus, there was an increase in IL-6, IGF-1, and FGF21 mRNA, with a decrease in FNDC5 mRNA and miR-150 levels. No correlation between soleus IL-6 or IGF-1 and trabecular bone parameters was found. However, FGF21 was negatively correlated with trabecular bone mineral content, whereas FNDC5 mRNA and miR-150 levels were positively correlated. These data suggest that modifications in FGF21, FNDC5, and miR-150 during muscle atrophy may mediate muscle-bone crosstalk and contribute to bone loss, while IL-6 and IGF-1 do not seem to play a predominant role.