Irisin promotes osteoblast proliferation and differentiation via activating the MAP kinase signaling pathways.
Irisin promotes osteoblast proliferation and differentiation via activating the MAP kinase signaling pathways.
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DOI：
10.1038/srep18732
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发表时间：
2016-01-07
影响因子：
4.6
通讯作者：
Xu L
中科院分区：
文献类型：
--
作者：
Qiao X;Nie Y;Ma Y;Chen Y;Cheng R;Yin W;Hu Y;Xu W;Xu L
体育锻炼能够改善骨骼健康。然而，机制知之甚少。Irisin是一种新的运动诱导的肌细胞因子，由骨骼肌在运动时分泌，已被证明在许多疾病中介导运动的有益作用。在目前的研究中，我们证明，鸢尾素促进成骨细胞增殖，并增加成骨细胞转录调节因子的表达，如Runt相关的转录因子-2，osterix/sp 7;成骨细胞分化标志物，包括碱性磷酸酶，胶原1型α-1，骨钙素和骨桥蛋白在体外。鸢尾素还能增加成骨细胞ALP活性和钙沉积。这些成骨作用是通过激活p38丝裂原活化蛋白激酶（p-p38 MAPK）和细胞外信号调节激酶（ERK）介导的。SB 023580或U 0126抑制p38 MAPK或pERK可阻断Irisin对Runx 2表达和ALP活性的上调作用。总之，我们的观察表明，鸢尾素直接靶向成骨细胞，促进成骨细胞的增殖和分化，通过激活P38/ERK MAP激酶信号级联反应在体外。鸢尾素能否作为骨质减少和骨质疏松症的治疗药物值得进一步研究。
Physical exercise is able to improve skeletal health. However, the mechanisms are poorly known. Irisin, a novel exercise-induced myokine, secreted by skeletal muscle in response to exercise, have been shown to mediate beneficial effects of exercise in many disorders. In the current study, we demonstrated that irisin promotes osteoblast proliferation, and increases the expression of osteoblastic transcription regulators, such as Runt-related transcription factor-2, osterix/sp7; and osteoblast differentiation markers, including alkaline phosphatase, collagen type 1 alpha-1, osteocalcin, and osteopontin in vitro. Irisin also increase ALP activity and calcium deposition in cultured osteoblast. These osteogenic effects were mediated by activating the p38 mitogen-activated protein kinase (p-p38 MAPK) and extracellular signal-regulated kinase (ERK). Inhibition of p38 MAPK by SB023580 or pERK by U0126 abolished the proliferation and up-regulatory effects of irisin on Runx2 expression and ALP activity. Together our observation suggest that irisin directly targets osteoblast, promoting osteoblast proliferation and differentiation via activating P38/ERK MAP kinase signaling cascades in vitro. Whether irisin can be utilized as the therapeutic agents for osteopenia and osteoporosis is worth to be further pursued.