Teriparatide Promotes Bone Marrow Mesenchymal Stem Cell Proliferation and Differentiation by Down-Regulating miR-339 to Target DLX5

Abstract

Osteoporosis (OP) is a metabolic bone disease which is characterized as loss of bone mineral content, decreased bone density, bone microstructural destruction, and reduced bone biomechanical evaluation index. Proliferation and differentiation of bone marrow mesenchymal stem cells (MSCs) is important for the treatment of OP. It is proposed that down-regulation of miR-339 can target DLX to promote the proliferation and differentiation of MSCs. However, whether teriparatide promotes osteogenic differentiation through this pathway remains unclear. MSCs were isolated from 4–6 week-old Wister rats. The effect of teriparatide on cell proliferation was evaluated by tetrazolium salt colorimetric method (MTT) and BrdU staining. Cell differentiation was measured by alkaline phosphatase staining. miR-339 expression was detected by real-time quantitative PCR (qRT-PCR). DLX5 expression was detected by Western-blot. It was found that teriparatide can promote the proliferation and differentiation of MSCs. MiR-339 level was significantly decreased and DLX5 expression was significantly upregulated after teriparatide treatment. After knocking down miR-339, teriparatide-induced upregulation of DLX5 by was attenuated. Teriparatide promotes the proliferation and differentiation of MSCs by down-regulating miR-339 to improve osteoporosis. It provides theoretical and experimental basis for the treatment of osteoporosis by teriparatide.