Periprosthetic osteolysis and the subsequent aseptic loosening can lead to the failure of joint replacement. Wear particles are well known to be the initiative cause inducing osteolysis through enhancing osteoclast‐mediated bone resorption and reducing osteogenic differentiation. The purpose of this study was to investigate the effects of osteoclast‐secreted exosomal long noncoding RNAs (lncRNAs) on osteogenesis in the process of particle‐induced osteolysis. RAW264.7 cells were treated by titanium particles (TI). The inflammatory cytokines were increased, and expression of Receptor Activator of Nuclear Factor‐κB and Nuclear factor of activated T cells c1 were also increased, indicating osteoclast differentiation occurred. The purified exosomes from RAW264.7 cells induced with TI inhibited osteogenic differentiation of MC3T3‐E1 cells. RNA sequencing generated lncRNAs expression profiles (458 up‐regulated and 1641 down‐regulated) of the exosomes derived from RAW264.7 cells treated with TI. Based on the results of gene ontology/Kyoto Encyclopedia of Genes and Genomes analysis and quantitative real time polymerase chain reaction validation, we confirmed two candidate lncRNAs, NONMMUT000375.2 and NONMMUT071578.2. The regulation network presented that some vital genes involved in osteoclast differentiation, such as Bcl2, Wnt11, TGF‐β, and Pdk1, were under the regulation of NONMMUT000375.2 and NONMMUT071578.2. Taken together, exosomes derived from TI treated RAW264.7 cells inhibit the osteogenic activity of MC3T3‐E1 cells. Exosomal lncRNAs, NONMMUT000375.2 and NONMMUT071578.2 may potentially play their roles in promoting osteoclast differentiation and suppressing osteogenesis, which aggravates the osteoclastogenesis/osteogenesis imbalance.

中文翻译：

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来自钛粒子处理的 RAW264.7 细胞的外泌体 lncRNA NONMMUT000375.2 和 NONMMUT071578.2 调节 MC3T3-E1 细胞的成骨分化。

假体周围骨质溶解和随后的无菌性松动可导致关节置换失败。众所周知，磨损颗粒是通过增强破骨细胞介导的骨吸收和减少成骨分化来诱导骨溶解的主动原因。本研究的目的是研究破骨细胞分泌的外泌体长非编码 RNA（lncRNA）在颗粒诱导的骨溶解过程中对成骨的影响。RAW264.7 细胞用钛颗粒 (TI) 处理。炎性细胞因子增加，核因子-κB受体激活因子和活化T细胞核因子c1的表达也增加，表明发生了破骨细胞分化。来自 TI 诱导的 RAW264.7 细胞的纯化外泌体抑制 MC3T3-E1 细胞的成骨分化。RNA测序产生了来自用TI处理的RAW264.7细胞的外泌体的lncRNAs表达谱（458个上调和1641个下调）。基于基因本体/京都基因与基因组百科全书分析和实时定量聚合酶链反应验证的结果，我们确认了两个候选 lncRNA，NONMMUT000375.2 和 NONMMUT071578.2。调控网络表明，一些参与破骨细胞分化的重要基因，如 Bcl2、Wnt11、TGF-β 和 Pdk1，受 NONMMUT000375.2 和 NONMMUT071578.2 的调控。总之，来自 TI 处理的 RAW264.7 细胞的外泌体抑制 MC3T3-E1 细胞的成骨活性。外泌体 lncRNA，NONMMUT000375.2 和 NONMMUT071578.2 可能在促进破骨细胞分化和抑制成骨方面发挥作用，