Insulin growth factor‑1 promotes the proliferation and osteogenic differentiation of bone marrow mesenchymal stem cells through the Wnt/β‑catenin pathway

Abstract

Bone marrow mesenchymal stem cells (BMSCs) are stem cells that exist in bone marrow tissue and have osteogenic differentiation potential. Insulin growth factor-1 (IGF-1) plays a key role in the proliferation and osteogenic differentiation of BMSCs. However, the specific mechanism of IGF-1 in cell proliferation and osteogenic differentiation remains unclear. In the present study, BMSCs were transfected with lentivirus carrying the siRNA-Wnt3a gene, and the Wnt3a level in BMSCs was revealed to be reduced by western blotting, real-time quantitative polymerase chain reaction and immunofluorescence detection. Then, BMSCs were treated with 80 ng/ml IGF-1 in complete medium for 5 days. CCK-8 and cell cycle assays revealed that cell proliferation was significantly decreased in the siRNA-Wnt3a group than in the control group. The protein and mRNA levels of β-catenin and cyclin D1 were significantly downregulated in the siRNA-Wnt3a group compared with the control group. In addition, BMSCs were treated with IGF-1 in osteogenic differentiation medium for 7 and 21 days, and alkaline phosphatase staining and Alizarin Red staining demonstrated significantly reduced osteogenic differentiation ability in the siRNA-Wnt3a group compared with the control group. Furthermore, the protein and mRNA levels of β-catenin, RUNX2, and OPN were downregulated compared with the control group. Our findings revealed that IGF-1 promoted the proliferation and differentiation of BMSCs at least partially through the Wnt/β-catenin pathway. These findings provided new insight into the clinical treatment of bone disease.

TGF-Beta Induced Key Genes of Osteogenic and Adipogenic Differentiation in Human Mesenchymal Stem Cells and MiRNA–mRNA Regulatory Networks

“…It is considered a cell adhesion protein, and osteoblasts cultured on a CTGF matrix exhibited enhanced bone nodule formation and matrix mineralization ( Hendesi et al, 2015 ). IGF1 is a multifunctional peptide growth factor that can induce strong proliferation and osteogenic differentiation in BMSCs ( Wu et al, 2020b ; Feng and Meng, 2021 ). During osteogenic differentiation, high expression of MMP13 in hMSCs grew on a type I collagen matrix.…”

Collagen Modulates the Biological Characteristics of WJ-MSCs in Basal and Osteoinduced Conditions

“…It had been shown to be more capable than BMP7 in inducing osteogenesis of BM-MSCs [ 50 ]. Furthermore, Feng and Meng [ 51 ] demonstrated that IGF1 promoted proliferation and osteogenesis in BM-MSCs via the Wnt/ β -catenin pathway.…”

Decisive gene strategy on osteoporosis: a comprehensive whole-literature-based approach for conclusive candidate gene targets

“…IGF1 also promotes osteoblasts’ growth and apoptosis in vivo via the phosphoinositide 3-kinase (PI3K) pathway [ 21 ] . Additionally, IGF1 can induce strong proliferation and osteogenic differentiation in bone marrow mesenchymal stem cells via Wnt/β-catenin and Akt signaling pathways [ 22 , 23 ]. In 2017, Chen et al [ 24 ] performed a meta-analysis on the correlation between IGF1 and osteoporosis in a Chinese population and found that rs35767 in IGF1 was associated with risks of osteoporosis (OR = 1.31, 95% CI = 1.18–1.47, P value < 0.001), whereas other loci (e.g., rs2288377 and rs5742612) in IGF1 were not significantly correlated with osteoporosis.…”