Colaianni Graziana, Grano Maria
Department of Basic Medical Science, Neuroscience and Sense Organs, University of Bari , Bari, Italy.
Bonekey Rep. 2015 Dec 23;4:765. doi: 10.1038/bonekey.2015.134. eCollection 2015.
Irisin was originally recognized as a hormone-like myokine secreted as a product of fibronectin type III domain containing 5 from skeletal muscle in response to exercise both in mice and humans. The first role attributed to Irisin was its ability to induce trans-differentiation of white adipose tissue into brown, but we recently demonstrated that Irisin also has a central role in the control of bone mass, even at lower concentration than required to induce the browning response. Considering how physical exercise is important for the development of an efficient load-bearing skeleton, we can now consider this myokine as one of the molecules responsible for the positive correlation between exercise and healthy bone, linking to the well-established relationship between muscle and bone. Recombinant Irisin (r-Irisin), administered at low dose in young mice, increases cortical bone mineral density and positively modifies bone geometry. Irisin exerts its effect prevalently on osteoblast lineage by enhancing differentiation and activity of bone-forming cells, through the increase in activating transcription factor 4 expression. Low-dose r-Irisin also increases osteopontin and decreases sclerostin synthesis but did not affect Uncoupling protein 1 expression in white adipose tissue, whose upregulation is known to cause browning of fat, when Irisin is administered at a higher dose. These findings offer an explanation to the positive outcome on the skeleton triggered by skeletal muscle during physical activity and prove that the bone tissue is more sensitive than the adipose tissue to the Irisin action.
鸢尾素最初被认为是一种类似激素的肌动蛋白，由小鼠和人类骨骼肌中含III型纤连蛋白结构域5的产物分泌产生，以响应运动。最初赋予鸢尾素的作用是其诱导白色脂肪组织向棕色脂肪组织转分化的能力，但我们最近证明，即使在低于诱导褐变反应所需的浓度下，鸢尾素在骨量控制中也起着核心作用。考虑到体育锻炼对高效承重骨骼发育的重要性，我们现在可以将这种肌动蛋白视为运动与健康骨骼之间正相关的分子之一，这与肌肉和骨骼之间已确立的关系相关。在幼鼠中低剂量给予重组鸢尾素（r-鸢尾素），可增加皮质骨矿物质密度并积极改变骨骼几何形状。鸢尾素主要通过增加激活转录因子4的表达，增强成骨细胞的分化和活性，从而对成骨细胞谱系发挥作用。低剂量的r-鸢尾素还可增加骨桥蛋白并减少硬化蛋白的合成，但在高剂量给予鸢尾素时，并不影响白色脂肪组织中解偶联蛋白1的表达，而解偶联蛋白1的上调已知会导致脂肪褐变。这些发现解释了体育活动期间骨骼肌对骨骼产生的积极影响，并证明骨组织比脂肪组织对鸢尾素的作用更敏感。
