Synergistic effects of miR-708-5p and miR-708-3p accelerate the progression of osteoporosis.

Background: Bone homeostasis is a tightly orchestrated process maintained by osteoblasts and osteoclasts, and a disruption of their steady-state equilibrium can lead to the occurrence of osteoporosis (OP).

Methods: We investigated the differential expression of micro (mi)RNAs in the bone tissues of a postmenopausal osteoporosis rat model induced by ovariectomy (OVX). Real-time PCR was used to verify the differentially expressed miRNAs in bone samples from OP patients and controls. The specific targets of two differentially expressed miRNAs in osteogenic or osteoclast differentiation were determined by bioinformatic prediction, and mRNA and protein detection.

Results: miR-708-5p and miR-708-3p were highly expressed in the bone tissue of OVX rats and OP patients. miR-708-5p negatively regulated osteoblast differentiation in bone marrow mesenchymal stem cells by targeting SMAD specific E3 ubiquitin protein ligase 2, while miR-708-3p positively regulated osteoclast differentiation in bone marrow monocytes by targeting cerebellar degeneration associated protein 1 antisense RNA. miR-708-5p and miR-708-3p were shown to originate from the same precursor miRNA and to have a synergistic effect on the development of osteoporosis with different temporal and spatial patterns.

Conclusion: Our findings provide a referential theoretical basis and targets for the prevention and treatment of osteoporosis.