The impact of light compressive stress on early bone remodeling and the expression profile of associated circRNAs

Abstract

Objectives The effects of mechanical stress on bone remodeling have been constantly studied by researchers at different levels, however several aspects still exist which are considerably unclear. The aim of this study was to investigate the response of osteoblasts exposed to different levels of compressive stress, to identify and perform a comprehensive analysis of the circRNA expression pattern as well as investigate their potential regulatory roles. Methods The gene and protein expression levels of Runx2, Alp, OCN, Rankl, and Opg were examined in MC3T3-E1 cells after exposure to varying levels of compressive stress. Whole transcriptome sequencing and qRT-PCR were used to identify the various differentially expressed circRNAs. Furthermore, MiRanda, Gene Ontology, Kyoto Encyclopedia of Genes and Genomes and Reactome enrichment analysis were used to predict the potential functions of the differentially expressed circRNAs. Results The osteoblastic and osteoclastic differentiation effects on the bone tissues were enhanced at 2g/cm2. 99 differentially expressed circRNAs were identified by whole transcriptome sequencing. They were predicted to interact with 1701 miRNAs, some of which play a crucial part in regulating osteogenic differentiation via the Wnt or Notch pathway. Conclusions This study suggested that 2g/cm2 compressive stress was sufficient to induce osteogeneis and bone tissue resorption. This was the first study to identify differentially expressed circRNAs and to integrate their potential ceRNA function during early bone remodeling after exposure to light compressive stress. These findings suggest that certain specific circRNAs might possess the potential to function as ceRNAs in order to promote bone remodeling.