Kaempferol promotes bone formation in part via the mTOR signaling pathway

Abstract

Previous research indicates that kaempferol (Kae) promotes osteogenesis, but its underlying mechanism of action remains unclear. The present study hypothesized that the osteogenic effects of Kae were mediated through mammalian target of rapamycin (mTor). To validate this hypothesis, bone marrow mesenchymal stem cells (BMScs) from ovariectomized (oVX) rats were differentiated into osteoblasts. The bone mineral density and bone microarchitecture of the oVX rats was measured in vivo, while osteogenesis was evaluated in vitro via alizarin red S staining and alkaline phosphatase activity measurements in cultured BMScs. The levels of phosphorylated eukaryotic translation initiation factor 4e-binding protein 1 (p-4e/BP1) and phosphorylated ribosomal protein S6 kinase B1 (p-S6K), and the expression of runt-related transcription factor 2 and Osterix, were concurrently quantified by western blot analysis. The data suggested that Kae prevented oVX-induced osteoporosis in rats by promoting osteoblastogenesis. Furthermore, treatment with Kae in rat BMScs enhanced mineralization, elevated alP activity, increased the expression levels of runx-2 and osterix and increased the levels of p-S6K and decreased the levels of p-4e/BP1 and, consistent with its ability to promote osteoblast differentiation. in contrast, treatment with rapamycin, an mTor inhibitor, produced the opposite phenotype. Taken together, these data suggested that the protective effects of Kae in BMScs and in the oVX rat model resulted from the induction of osteogenesis via mTor signaling, or at least partially via the regulation of downstream effectors of the mTor pathway.

[Retracted] Shared Genetic and Epigenetic Mechanisms between the Osteogenic Differentiation of Dental Pulp Stem Cells and Bone Marrow Stem Cells

“…In BMSCs, the osteosuppressing effect of TNF- α is exerted through the downregulation of miR-34a and miR-21 expression [ 73 ], which are listed among the top 30 dysregulated DEmiRNAs in osteodifferentiation of BMSCs. The mTOR signaling pathway is activated by stimulation with dexamethasone and kaempferol in DPSCs and BMSCs, respectively, suggesting mTOR as a common pathway in the course of their osteogenesis [ 74 , 75 ]. Hippo signaling pathway promotes osteogenic differentiation in DPSCs upon regulation by SOX2 and the downstream BMP signaling [ 76 ].…”

Preparation and characterization of 58S bioactive glass based scaffold with Kaempferol‐containing Zein coating for bone tissue engineering

“…shown in Figure 7 indicating that it was not toxic for cells while according to the previous report, 43 is desirable for stem cell differentiation into osteoblast and bone formation. In similar research, 19 tetracycline release from Zein-coated scaffold was investigated for 10 days.…”

Predicting and Exploring the Mechanisms of Erzhi Pill in Prevention and Treatment of Osteoporosis Based on Network Pharmacology and Zebrafish Experiments

“… 27 , 28 Ursolic acid can promote bone formation, improve the activity of osteoblasts and inhibit the activity of osteoclasts so as to prevent OP. 29 , 30 Kaempferol stimulates bone marrow mesenchymal stem cells (BMSCs) to differentiate into osteoblasts by regulating mTOR pathway, 31 and stimulates estrogen signaling followed by WNT pathway activation to achieve its potential for bone-sparing effects. 32 Notably, nicotine, the active compound predicted in this study, has a variety of pharmacological activities and is thought to contribute to the onset of several diseases, including OP.…”