Irisin promotes proliferation but inhibits differentiation in osteoclast precursor cells
Irisin promotes proliferation but inhibits differentiation in osteoclast precursor cells
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DOI：
10.1096/fj.201700983rr
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发表时间：
2018-11-01
期刊：
影响因子：
4.8
通讯作者：
Xu, Liangzhi
中科院分区：
文献类型：
--
作者：
Ma, Yaxian;Qiao, Xiaoyong;Xu, Liangzhi
NF-B配体诱导破骨细胞分化的受体激活剂在骨代谢过程中发挥关键作用。破骨细胞过度活化可导致一系列疾病。Irisin是2012年首次报道的一种新型肌因子，已被提出介导运动的有益代谢效应。研究表明，鸢尾素通过促进成骨细胞增殖和分化而靶向成骨细胞;然而，关于鸢尾素对破骨细胞的作用的潜在机制仍然是难以捉摸的。利用两种类型的破骨细胞前体细胞，RAW 264.7细胞和小鼠骨髓单核细胞，我们发现，鸢尾素促进破骨细胞前体细胞增殖，但抑制破骨细胞分化。Irisin下调破骨细胞分化标志基因的表达，包括NF-B受体活化剂、活化T细胞核因子、胞质1、组织蛋白酶K和抗酒石酸酸性磷酸酶（TRAP），以及减少TRAP阳性多核细胞和羟基磷灰石吸收陷窝的数量。此外，我们发现，鸢尾素抑制NF-B信号通路，但激活p38和JNK信号通路。在p38和JNK的抑制剂的存在下，鸢尾素诱导的促进RAW 264.7细胞增殖减弱。然而，鸢尾素诱导的破骨细胞分化抑制不受p38或JNK信号通路的影响。我们的研究表明了鸢尾素对破骨细胞生成的直接作用，并揭示了鸢尾素在骨代谢疾病中的治疗潜力的机制。乔，X.，曾，R.，郑河，英-地张杰，Luo，Y.，（1996年），美国，聂，Y.，Hu，Y.，杨志，张杰，刘，L.，徐伟，Xu，C. C.的方法，许湖，加-地鸢尾素促进破骨细胞前体细胞增殖但抑制其分化。
The receptor activator of NF-B ligand-induced osteoclast differentiation has a critical role in the process of bone metabolism. Overactivation of osteoclastogenesis may result in a series of diseases. Irisin, a novel myokine, which was first reported in 2012, has been proposed to mediate the beneficial metabolic effects of exercise. Studies have demonstrated that irisin targets osteoblasts by promoting osteoblast proliferation and differentiation; however, the underlying mechanism regarding the effect of irisin on osteoclasts remains elusive. Using 2 types of osteoclast precursor cells, RAW264.7 cells and mouse bone marrow monocytes, we showed that irisin promoted osteoclast precursor cell proliferation but inhibited osteoclast differentiation. Irisin down-regulated the expression of osteoclast differentiation marker genes, including receptor activators of NF-B, nuclear factor of activated T cells, cytoplasmic 1, cathepsin K, and tartrate-resistant acid phosphatase (TRAP), as well as decreasing the number of TRAP-positive multinucleated cells and hydroxyapatite resorption pits. Furthermore, we showed that irisin suppressed the NF-B signaling pathway, but activated the p38 and JNK signaling pathways. In the presence of an inhibitor of p38 and JNK, irisin-induced promotion of RAW264.7 cell proliferation was attenuated. However, irisin-induced inhibition of osteoclast differentiation was not affected by either the p38 or JNK signaling pathway. Our study suggested the direct effect of irisin on osteoclastogenesis and revealed the mechanism responsible for the therapeutic potential of irisin in bone metabolism disease.Ma, Y., Qiao, X., Zeng, R., Cheng, R., Zhang, J., Luo, Y., Nie, Y., Hu, Y., Yang, Z., Zhang, J., Liu, L., Xu, W., Xu, C. C., Xu, L. Irisin promotes proliferation but inhibits differentiation in osteoclast precursor cells.