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The function and mechanism of the miR-210-3p/KRAS axis in bone marrow-derived mesenchymal stem cell from patients with osteoporosis

Minghua Hu 1Xi Zhu 2Heng Yuan 3Haifeng Li 3Hongchun Liao 1Shijie Chen 4

J Tissue Eng Regen Med doi: 10.1002/term.3215. 

Abstract

The disturbance of homeostasis in bone marrow-derived mesenchymal stem cell (BMSC) adipogenesis and osteogenesis could result in pathologic consequences that plays a critical role in osteoporosis pathogenesis. In the present study, we demonstrated that miR-210-3p was abnormally upregulated within the femur of osteoporosis patients and abnormally downregulated in osteogenically differentiated BMSCs. The predicted targets of candidate miRNAs were enriched in the Pluripotent stem cell differentiation signaling. KRAS, as a vital factor of the KRAS/MAPK/ERK signaling, was upregulated in osteogenically differentiated BMSCs. In osteoporosis-BMSCs, the expression level of KRAS showed to be decreased, whereas the expression level of miR-210-3p showed to be increased. Within normal-BMSCs, miR-210-3p overexpression or KRAS silencing significantly inhibited the osteogenic differentiation and the activation of the MAPK signaling. miR-210-3p directly targeted KRAS and inhibited KRAS expression. The effects of miR-210-3p overexpression upon KRAS expression, MAPK signaling, and BMSC osteogenic differentiation were significantly reversed by KRAS overexpression. Altogether, miR-210-3p suppresses normal BMSC osteogenic differentiation through targeting KRAS and suppressing the MAPK signaling; KRAS overexpression could reverse the suppressive effects of miR-210-3p overexpression.