Osteoclast-derived exosomal miR-214-3p inhibits osteoblastic bone formation.
Osteoclast-derived exosomal miR-214-3p inhibits osteoblastic bone formation.
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破骨细胞来源的外泌体 miR-214-3p 抑制成骨细胞骨形成
DOI：
10.1038/ncomms10872
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发表时间：
2016-03-07
影响因子：
16.6
通讯作者：
Zhang G
中科院分区：
文献类型：
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作者：
Li D;Liu J;Guo B;Liang C;Dang L;Lu C;He X;Cheung HY;Xu L;Lu C;He B;Liu B;Shaikh AB;Li F;Wang L;Yang Z;Au DW;Peng S;Zhang Z;Zhang BT;Pan X;Qian A;Shang P;Xiao L;Jiang B;Wong CK;Xu J;Bian Z;Liang Z;Guo DA;Zhu H;Tan W;Lu A;Zhang G
新出现的证据表明破骨细胞指导成骨细胞骨形成。microRNAs（miRNAs）在调节破骨细胞和成骨细胞功能中具有重要作用。然而，miRNA是否介导破骨细胞介导的成骨细胞骨形成尚不清楚。在这里，我们发现骨细胞miR-214 - 3p的增加与血清外泌体miR-214 - 3p的升高和骨折老年妇女和卵巢切除（OVX）小鼠骨形成的减少有关。破骨细胞特异性miR-214 - 3p敲入小鼠具有升高的血清外泌体miR-214 - 3p和减少的骨形成，其通过破骨细胞靶向miR-214 - 3p治疗来挽救。我们进一步证明，破骨细胞来源的外泌体miR-214 - 3p被转移到成骨细胞，以抑制体外成骨细胞活性并减少体内骨形成。此外，破骨细胞靶向的miR-214 - 3p抑制可促进衰老OVX小鼠的骨形成。总的来说，我们的研究结果表明，破骨细胞来源的外泌体miR-214 - 3p转移到成骨细胞，以抑制骨形成。抑制破骨细胞中的miR-214 - 3p可能是治疗涉及骨形成减少的骨骼疾病的策略。 在以前的研究中，作者发现miR-214抑制成骨细胞骨形成。在这里，他们扩展了这些发现，使用卵巢切除小鼠和骨折患者的样本，以表明miR-214是破骨细胞-成骨细胞串扰的介质。
Emerging evidence indicates that osteoclasts direct osteoblastic bone formation. MicroRNAs (miRNAs) have a crucial role in regulating osteoclast and osteoblast function. However, whether miRNAs mediate osteoclast-directed osteoblastic bone formation is mostly unknown. Here, we show that increased osteoclastic miR-214-3p associates with both elevated serum exosomal miR-214-3p and reduced bone formation in elderly women with fractures and in ovariectomized (OVX) mice. Osteoclast-specific miR-214-3p knock-in mice have elevated serum exosomal miR-214-3p and reduced bone formation that is rescued by osteoclast-targeted antagomir-214-3p treatment. We further demonstrate that osteoclast-derived exosomal miR-214-3p is transferred to osteoblasts to inhibit osteoblast activity in vitro and reduce bone formation in vivo. Moreover, osteoclast-targeted miR-214-3p inhibition promotes bone formation in ageing OVX mice. Collectively, our results suggest that osteoclast-derived exosomal miR-214-3p transfers to osteoblasts to inhibit bone formation. Inhibition of miR-214-3p in osteoclasts may be a strategy for treating skeletal disorders involving a reduction in bone formation. In previous studies the authors discovered that miR-214 inhibits osteoblastic bone formation. Here they extend on these findings, using ovariectomized mice and samples from patients with bone fractures, to show that miR-214 is a mediator of osteoclast-osteoblast crosstalk.