Astragaloside IV Improves Tibial Defect in Rats and Promotes Proliferation and Osteogenic Differentiation of hBMSCs through MiR-124-3p.1/STAT3 Axis

Abstract

Astragaloside IV (AST-IV) facilitates the proliferation and migration of osteoblastlike cells. We sought to explore the effect and potential mechanism of AST-IV on regeneration of tibial defects. To reveal the effect of AST-IV on regeneration of tibial defects in rat, HE staining and microcomputed tomography (μCT) were performed on tibial bone. The binding relationship between miR-124-3p.1 and STAT3 was analyzed by TargetScan V7.2 and a dual-luciferase reporter assay. Human bone marrow mesenchymal stromal/stem cells (hBMSCs) were identified by morphological observation and flow-cytometric analysis. To reveal the effect and mechanism of AST-IV on phenotypes of hBMSCs, hBMSCs were treated with AST-IV, miR-124-3p.1 mimic, and pcDNA-STAT3, and cell viability, cell cycle, ALP activity, and calcium deposition of hBMSCs in vitro were determined by MTT, flow-cytometric analysis, ELISA, and Alizarin red staining, respectively. The expressions of osteoblast marker molecules (RUNX2, OCN, Smad4), miR-124-3p.1, and STAT3 were indicated by RT-qPCR and Western blot. AST-IV decreased miR-124-3p.1 expression, increased STAT3 expression in tibial bone defects, and promoted regeneration of tibial bone defects in a concentration-dependent manner. The hBMSCs appeared spindle-shaped and were positive for CD105, but negative for CD34. MiR-124-3p.1 negatively regulated STAT3 expression in hBMSCs under osteogenic conditions. AST-IV promoted viability, cell cycle, ALP activity, and osteogenic differentiation of hBMSCs along with increased expressions of osteoblast marker molecules, which was partially reversed by miR-124-3p.1 overexpression. However, the effect of miR-124-3p.1 overexpression on hBMSCs was also partially reversed by STAT3 overexpression. AST-IV improves tibial defects in rats and promotes proliferation and osteogenic differentiation of hBMSCs through the miR-124-3p.1/STAT3 axis.

miRNA-124-3p.1 Inhibits the Osteogenic and Odontogenic Differentiation of SCAPs via MACF1/smad7 Axis

“…Previous studies have demonstrated that miRNAs act as important regulators for the stemness of oral mesenchymal stem cells [37,38]. Recently, the critical role of miR-124-3p.1 in osteogenic differentiation of human BMSCs has been previously demonstrated [34]. We, therefore, assume that miR-124-3p.1 can inhibit osteogenic and odontogenic differentiation of SCAPs through the MACF1/smad7 axis.…”

“…Moreover, miR-124-3p.1 sensitizes carboplatin induced mitochondrial apoptosis by inhibiting CAV1 in ovarian cancer [33]. Recently, there are studies demonstrated that miR-124-3p.1 overexpression negatively regulated proliferation and osteogenic differentiation of human bone marrow mesenchymal stem cells (BMSCs) [34]. However, the role of miR-124-3p.1 in the differentiation of SCAPs are still unclear.…”

Combination of ultra‐performance liquid chromatography‐quadrupole time‐of‐flight mass spectrometry and network pharmacology to reveal the mechanism of Shengyu Decoction for treating anemia

“…Bone marrow mesenchymal stem cells, the important component, and regulator of the bone marrow microenvironment have the role of supporting hematopoiesis [ 28 ]. It has been reported that astragaloside A can promote the proliferation and osteogenic differentiation of bone marrow mesenchymal stem cells [ 29 ], and ferulic acid also has the same effect [ 30 ]. Furthermore, some scholars have shown that ferulic acid, calycosin, and astragaloside A can be used alone or in combination to increase the content of RBC, WBC, and HGB [ 31 ], which was supported by our peripheral blood tests.…”

lncRNA FGD5-AS1 Regulates Bone Marrow Stem Cell Proliferation and Apoptosis by Affecting miR-296-5p/STAT3 Axis in Steroid-Induced Osteonecrosis of the Femoral Head

“…Previous studies have shown that miR-296-5p also directly targeted STAT3 in colorectal cancer and non-small cell lung cancer [ 25 , 26 ]. STAT3 has been reported to promote proliferation and osteogenic differentiation of hBMSCs [ 27 ]. Consistent with our results, STAT3 was also found to promote cell proliferation and differentiation and restrains apoptosis in Dex-treated hBMSCs.…”