MiR-486–3p promotes osteogenic differentiation of BMSC by targeting CTNNBIP1 and activating the Wnt/β-catenin pathway

• Published in: Biochemical and biophysical research communications Vol. 566; pp. 59 - 66
• Main Authors: Zhang, Zheng, Jiang, Weiwei, Hu, Miao, Gao, Rui, Zhou, Xuhui
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 20.08.2021
• Subjects: alizarin; alkaline phosphatase; Animals; beta Catenin - genetics; bioluminescence assay; bone formation; bone marrow; Bone metabolism; bone resorption; Catenin beta interacting protein 1; Cell Differentiation; Cells, Cultured; cyclins; Female; Gene Expression Regulation; humans; Lentivirus; Mesenchymal Stem Cells - cytology; Mesenchymal Stem Cells - metabolism; Mice; Mice, Inbred C57BL; MicroRNAs - genetics; miR-486–3p; Osteogenesis; Osteogenic differentiation; Osteoporosis; ovariectomy; Wnt Signaling Pathway; Wnt/β-catenin pathway; Osteoporosis; Wnt/β-catenin pathway; miR-486–3p; Osteogenic differentiation; Bone metabolism; Catenin beta interacting protein 1
• ISSN: 0006-291X; 1090-2104; 1090-2104
• DOI: 10.1016/j.bbrc.2021.05.098

Dysfunction in the osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) leads to bone loss/osteoporosis. The catenin beta interacting protein 1 (CTNNBIP1) is an inhibitor of Wnt/β-catenin signaling, whose role in osteogenesis remains elusive. This study aimed to reveal the effects of miR-486–3p/CTNNBIP1 in osteogenesis. Bone marrow samples from healthy individuals and osteoporosis patients and mice with sham or ovariectomy (OVX) surgeries were collected. Levels of CTNNBIP1 and miR-486–3p were assessed. A dual-luciferase reporter assay was used to confirm the interactions between CTNNBIP1 and miR-486–3p. MiR-486–3p mimics/inhibitor or CTNNBIP1 overexpression lentiviruses were transfected to human BMSCs (hBMSCs) and an osteogenic assay was performed. Alizarin red S (ARS) and Alkaline phosphatase (ALP) intensity and expression of osteogenic genes Runx2, Alp, Cola1 and Bglap were measured. Key proteins in the Wnt/β-catenin pathway including active β-catenin, Bcl-2, and Cyclin D1 were assessed. CTNNBIP1 was upregulated while miR-486–3p was downregulated in osteoporosis patients and OVX mice. CTNNBIP1 was confirmed as a target of miR-486–3p. MiR-486–3p overexpression promoted, while miR-486–3p knockdown suppressed, osteogenic differentiation and Wnt/β-catenin signaling. Rescue experiments confirmed the negative effects of CTNNBIP1 overexpression on osteoblastic differentiation and that miR-486–3p mimics could reverse canonical Wnt signaling. This study demonstrated that miR-486–3p targets CTNNBIP1, thus activating the Wnt/β-catenin signaling pathway to promote osteogenesis of BMSCs. [Display omitted] •miR-486–3p is a positive regulator in osteogenic differentiation.•miR-486–3p target the 3′UTR of CTNNBIP1 mRNA.•miR-486–3p/CTNNBIP1 axis regulates Wnt/β-catenin signaling to control osteogenesis.