In vivo and in vitro effects of PTH1-34 on osteogenic and adipogenic differentiation of human bone marrow-derived mesenchymal stem cells through regulating microRNA-155.

Abstract

This study aimed to investigate the effect of parathyroid hormone (PTH1-34) on osteogenic and adipogenic differentiation of hBMSCs by the regulation of miR-155. A total of 36 adult volunteers were selected in this study. Effects of PTH1-34 on the proliferation of hBMSCs and miR-155 expression were investigated using a MTT assay. The hBMSCs were divided into blank, PTH1-34, miR-155 mimic, miR-155 mimic negative control (NC), miR-155 inhibitor, miR-155 inhibitor NC, PTH1-34 + miR-155 mimic, PTH1-34 + miR-155 inhibitor, and NPS R-568 groups. Postmenopausal osteoporosis (PMOP) mouse models were established by ovariectomy (OVX) and divided into ten groups. The RT-qPCR and Western blotting assay were carried out to detect the expression of osteogenesis/adipogenic-related genes and miR-155, and osteogenesis/adipogenic-related proteins. PTH1-34 could promote hBMSCs proliferation and inhibit miR-155 expression in a dose-dependent manner. Compared with the blank control group, expressions of Runx2, and BSP was up-regulated in the PTH1-34 and miR-155 inhibitor groups, while expressions of miR-155, PPAR-γ, lipoprotein lipase (LPL), fatty acid binding protein 4 (Fabp4), adiponectin, and CCAAT/enhancer binding protein α (C/EBPα) were down-regulated. In the in vivo experiment, compared with the OVX group, the BMD and expressions of Runx2 and BSP was up-regulated in the PTH1-34, miR-155 inhibitor, and PTH1-34 + miR-155 inhibitor groups, while expressions of PPAR-γ, LPL, Fabp4, adiponectin, and C/EBPα were down-regulated. The miR-155 mimic and NPS R-568 groups followed opposite trends. PTH1-34 could promote the osteogenic differentiation and inhibits adipogenic differentiation of hBMSCs through down-regulating miR-155 in PMOP mice.