Plasma Exosomal miR-106b-5p Is Associated With Osteoporosis by Targeting SMAD5, BMP2, and MAPK1 Genes

This study aimed to explore the expression, function, and regulatory mechanism of exosomal miR-106b-5p in osteoporosis (OP), to identify a novel diagnostic biomarkers and therapeutic targets.

Plasma-derived exosomes were isolated in three independent case-control study samples (N=278, OP patients vs. healthy controls=139:139) to identify OP-associated miRNAs. Lentivirus-infected MC3T3-E1 and RAW264.7 cells were used to investigate the impact of upregulated miR-106b-5p on the proliferation, apoptosis, and differentiation of osteoblasts and osteoclasts, respectively. Target genes were predicted via bioinformatics.

Exosomal miR-106b-5p abundance was screened to be consistently up-regulated with OP in the three sample sets. Overexpression of miR-106b-5p significantly affected proliferation, apoptosis, and cell cycle of MC3T3-E1 but not RAW264.7. RT-qPCR, ALP and TRAP staining showed that the upregulated miR-106b-5p significantly inhibits osteogenic differentiation and enhances bone resorption. Additionally, miR-106b-5p was confirmed to target and negatively regulate expression of SMAD5, BMP2, and MAPK1 genes.

Plasma exosomal miR-106b-5p promotes OP by targeting SMAD5/BMP2/MAPK1 to suppress bone formation and enhance resorption, representing a potential diagnostic biomarker and therapeutic target.