Krüppel-like factor 4 promotes the proliferation and osteogenic differentiation of BMSCs through SOX2/IGF2 pathway

Abstract

Objectives: Human bone marrow mesenchymal stem cells (BMSCs) have multi-lineage differentiation potential and have been widely researched in regenerative medicine. The purpose of this research was to explore whether Krüppel-like factor 4 (KLF4) can regulate the osteogenic differentiation of BMSCs. Methods: We transfected human BMSCs with KLF4 overexpression plasmid and si-KLF4 to study the effects of KLF4. We performed cell proliferation assay, flow cytometry and Alizarin Red staining on BMSCs. Quantitative real-time PCR and western blot was performed to determined mRNA and protein expression of osteogenic differentiation markers, KLF4, SOX2 and IGF2. Bone defect animal model was created and the adenovirus containing KLF4 overexpression or knockdown plasmid was injected. Finally, HE staining was performed on tibia to assess the new bone formation. Results: Our results showed that KLF4 promotes not only the growth of BMSCs, but also their osteogenic differentiation. Also, it mediated these effects through SOX2/IGF2 signaling pathway. In addition, KLF4 overexpression could increase the bone regeneration in in-vivo model, whereas KLF4 knockdown decreased the bone regeneration. Conclusions: KLF4 regulates BMSC’s osteogenic differentiation via SOX2/IGF2 pathway.

Exploring the mechanism of Astragali radix for promoting osteogenic differentiation based on network pharmacology, molecular docking, and experimental validation

“…Traditional Chinese medicine has played an important role in the treatment of OP. Multiple studies have confirmed the effect of different herbal medicines on the osteogenic differentiation of BM-MSCs (Chen et al, 2019;Fei et al, 2022;Huang et al, 2020;Song et al, 2022;Teng et al, 2022). However, the mechanism by which AR alleviates OP by promoting osteogenesis differentiation has not been adequately studied to date.…”

“…Therefore, the ability to promote osteogenic differentiation of BM‐MSCs may provide an effective approach for the treatment of OP (Chen et al, 2016). It has been demonstrated that the ability of BM‐MSC osteogenic differentiation can be promoted through different pathways, such as the BMP2‐Wnt/β‐catenin/HIF‐1α/SOX2/IGF2 pathway (Fei et al, 2022; Sun, Zhang, et al, 2022; Yuan et al, 2022). Traditional Chinese medicine has played an important role in the treatment of OP.…”

Hepatocyte growth factor and insulin-like growth factor-1 were used to repair bone-cartilage defects in bone marrow mesenchymal stem cells in a rabbit model of postmenopausal

“…At present, the implantation capacity of MSCs is poor, and frequent inflammation and ischemia limit the homing and survival of MSCs in vivo, leading to suboptimal repair of osteochondral defects [16][17][18][19]. Growth factors (GFs) are a class of proteins that guide cell differentiation and gene expression and regulate cell behavior by activating intracellular signaling pathways [20,21]. GFs are key drivers in tissue regeneration.…”