Abstract

Background Acidic fibroblast growth factor (aFGF) is considered to be a key regulator for bone marrow mesenchymal stem cells (BMSCs), which are critical mediators of the tendon-bone healing process. However, how aFGF regulates BMSCs cellular behavior and promotes tendon-bone healing at multiple molecular levels has yet to be fully elucidated. Methods Based on the experimental model of aFGF-treated bone marrow mesenchymal stem cells (BMSCs) from rabbit ( Oryctolagus cuniculus ), deep multi-omics sequencing was conducted on the aFGF treatment group and the control group (n = 3), encompassing transcriptome (RNA sequencing, RNA-Seq), proteome (data-independent acquisition, DIA) and microRNA sequencing (miRNA-Seq). Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) were used to analyze the differentially expressed genes (DEGs), differentially expressed proteins (DEPs), and differentially expressed miRNA prediction genes (DEmiRPGs). Multiple omics data sets were further analyzed by Data Integration Analysis for Biomarker Discovery using Latent Components (DIABLO). The candidate regulatory axes were screened, and the enrichment analysis of related genes was assessed by GO and KEGG. Results By screening and analyzing the DEmiRPGs/DEGs/DEPs in aFGF-treated BMSCs and control BMSCs, aFGF activated several pathways, including cell proliferation, cell cycle, phosphatidylinositide 3-kinases (PI3K)-protein kinase B (Akt) signaling pathway, mitogen-activated protein kinase (MAPK) signaling pathway, and extracellular matrix (ECM)-receptor interaction. DIABLO analysis showed that most of the significantly changed molecules were located in the synergistic up/down regions. Through the screening of candidate regulatory axis, the key regulatory axis of miR-29-y/notch homolog 2 (NOTCH2) was identified in this study, which may be one of the core mechanisms of aFGF’s pro-healing function. Conclusion This study identifies the miR-29-y/NOTCH2 axis as a key regulatory hub i