Long noncoding RNAs (lncRNAs) have been regarded as important regulators in numerous biological processes during cell development. However, the holistic lncRNA expression pattern and potential functions during osteoblast differentiation under simulated microgravity remain unknown. In the present study, a high throughput microarray assay was performed to detect lncRNA and mRNA expression profiles during MC3TC‑E1 pre‑osteoblast cell osteo‑differentiation under simulated microgravity. The expression of 857 lncRNAs and 2,264 mRNAs was signi-ficantly altered when MC3T3‑E1 cells were exposed to simulated microgravity. A relatively consistent distribution pattern on the chromosome and a co‑expression network were observed between the differentially‑expressed lncRNAs and mRNAs. Genomic context analysis further identified 132 differentially‑expressed lncRNAs and nearby coding gene pairs. Subsequently, 3 lncRNAs were screened out for their possible function in osteoblast differentiation, based on their co‑expression association and potential cis‑acting regulatory pattern with the deregulated mRNAs. The present study aimed to provide a comprehensive understanding of and a foundation for future studies into lncRNA function in mechanical signal‑mediated osteoblast differentiation.