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.

[Retracted] Exosome: Function and Application in Inflammatory Bone Diseases

“…miR-23a-5p-containing exosomes effectively inhibit Runx2 and promote Yes-associated protein-1- (YAP1-) mediated MT1DP by suppressing osteoblast differentiation. Exosomes produced by RAW 264.7 cells after titanium particle treatment inhibit the differentiation of MC3T3-E1 cells [ 100 ]. The analysis of differentially expressed lncRNAs in exosomes produced by RAW 264.7 cells revealed that lncRNA NONMMUT000375.2 and lncRNA NONMMUT071578.2 might play an essential role in inhibiting osteoblast differentiation.…”

Effects of Bioactive Glasses (BGs) on Exosome Production and Secretion: A Critical Review

“…The composition of the applied biomaterials directly affects the type and activity of the released exosomes [59]. Previous studies have confirmed that bioceramics can influence the production of specific types of exosomes in mammalian cells, which can lead to an improved tissue-healing process through the activation and enhancement of biological phenomena such as osteogenesis and angiogenesis [60][61][62][63][64]. In this regard, Lin et al showed that strontium-substituted calcium silicates (Sr-CS) can promote neovascularization through the activation of human umbilical vein endothelial cells (HUVECs) to produce and secrete proangiogenic miR-146a-containing exosomes, and the inhibition of Smad4 and NF2 proteins [65].…”

Bone Cell Exosomes and Emerging Strategies in Bone Engineering

“…In another study, exosomes from the macrophages treated with Titanium particles inhibited osteogenic differentiation. RNA sequencing and gene ontology studies have revealed the role of two long non-coding RNAs-NONMMUT000375.2 and NONMMUT071578.2-in suppressing osteogenesis through regulation of genes Bcl2, Wnt11, TGF-β, and Pdk1 [220]. There are also recent indications that the doping of biomaterials with certain trace elements has been shown to influence the exosome cargo of mesenchymal stem cells towards enhanced angiogenic potential.…”