Exosomal lncRNAs NONMMUT000375.2 and NONMMUT071578.2 derived from titanium particle treated RAW264.7 cells regulate osteogenic differentiation of MC3T3-E1 cells.

Abstract

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.