LGR5 enhances the osteoblastic differentiation of MC3T3‑E1 cells through the Wnt/β‑catenin pathway

Yu, Wei; Xie, Chaoran; Chen, Fancheng; Cheng, Pei Feng; Yang, Lei; Pan, Xiaoyun

doi:10.3892/etm.2021.10321

Cited by 6 publications

(4 citation statements)

References 37 publications

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“…Multiple studies have shown that the expression of Wnt6, Wnt10a, and Wnt10b inhibits the differentiation of MSCs into adipocytes while promoting MSCs differentiation into osteoblasts through the canonical Wnt pathway [34]. Furthermore, lots of studies have revealed that Wnt/β-catenin plays an important role in the proliferation and differentiation of embryonic osteoblasts [35,36]. Met also activated the Wnt/βcatenin signaling pathway to reduce inflammation and apoptosis, according to Zhang et al [37].…”

Section: Discussionmentioning

confidence: 99%

Metformin activates Wnt/β-catenin for the treatment of diabetic osteoporosis

Huang

Liang

et al. 2022

BMC Endocr Disord

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Background With the deepening of social aging, the incidence rate of osteoporosis and diabetes continues to rise. More and more clinical studies show that diabetes is highly correlated with osteoporosis. Diabetes osteoporosis is considered as a metabolic bone disease of diabetes patients. This study aims to explore the role and mechanism of metformin (Met) in diabetic osteoporosis. Methods Mouse MC3T3-E1 cells were treated with Met (0.5 mM) and exposed to high glucose (HG, 35 mM). The cells were cultured in an osteogenic medium for osteogenic differentiation, and the cell proliferation ability was determined using Cell Counting Kit-8; Alkaline phosphatase (ALP) activity detection and alizarin red staining were utilized to evaluate the effect of Met on MC3T3-E1 osteogenic differentiation. Western blot was used to detect the expressions of osteogenesis-related proteins (Runx2 and OCN) as well as Wnt/β-catenin signaling pathway-related proteins in MC3T3-E1 cells. Results HG inhibited proliferation and calcification of MC3T3-E1 cells, down-regulated ALP activity, and the expression of Runx2 and OCN in MC3T3-E1 cells. Meanwhile, the activity of the Wnt/β-catenin signaling pathway was inhibited. Met treatment was found to significantly stimulate the proliferation and calcification of MC3T3-E1 cells under HG conditions, as well as increase the ALP activity and the protein expression level of Runx2 and OCN in the cells. As a result, osteogenic differentiation was promoted and osteoporosis was alleviated. Apart from this, Met also increased the protein expression level of Wnt1, β-catenin, and C-myc to activate the Wnt/β-catenin signaling pathway. Conclusion Met can stimulate the proliferation and osteogenic differentiation of MC3T3-E1 cells under HG conditions. Met may also treat diabetic osteoporosis through Wnt/β-catenin activation.

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Section: Discussionmentioning

confidence: 99%

Metformin activates Wnt/β-catenin for the treatment of diabetic osteoporosis

Huang

Liang

et al. 2022

BMC Endocr Disord

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“…Lu et al [38] also found that NMN relieved senescence in osteoblasts and improved bone repair in osteoporotic mice. The Wnt/β-catenin signaling pathway has been shown to stimulate bone formation and remodeling during osteogenesis [29], and various studies have demonstrated that osteogenic differentiation was induced in MC3T3-E1 cells via the Wnt/β-catenin signaling pathway [33,39,40]. However, to date, no research has clarified whether NMN can ameliorate LPS-induced impairment of osteogenesis or if NMN's influence on osteogenesis is mediated by the Wnt/ β-catenin signaling pathway.…”

Section: Discussionmentioning

confidence: 99%

Effect of nicotinamide mononucleotide on osteogenesis in MC3T3-E1 cells against inflammation-induced by lipopolysaccharide

Kang,

Koo,

Jun

et al. 2024

Clin Exp Reprod Med

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Objective: Nicotinamide mononucleotide (NMN) is extensively utilized as an anti-aging agent and possesses anti-inflammatory properties. Lipopolysaccharide (LPS) activates Toll-like receptor 4, a process modulated by intracellular signaling pathways such as the Wnt/β-catenin pathway. This study investigated the impact of NMN on osteogenesis in the presence of LPS. Methods: To elucidate the role of NMN in osteogenesis in the context of Gram-negative bacterial infection after LPS treatment, we cultured a mouse pre-osteoblast cell line (MC3T3-E1) and subsequently incubated it with NMN and/or LPS. We then evaluated osteogenic activity by measuring alkaline phosphatase activity, assessing gene expression and protein levels, and performing Alizarin Red S staining and immunocytochemistry.Results: MC3T3-E1 cells underwent successful differentiation into osteoblasts following treatment with osteogenic induction medium. LPS diminished features related to osteogenic differentiation, which were subsequently partially reversed by treatment with NMN. The restorative effects of NMN on LPS-exposed MC3T3-E1 cells were further substantiated by elucidating the role of Wnt/β-catenin signaling, as confirmed through immunocytochemistry. Conclusion: This study showed that infection with Gram-negative bacteria disrupted the osteogenic differentiation of MC3T3-E1 cells. This adverse effect was partially reversed by administering a high-dose of NMN. Drawing on these results, we propose that NMN could serve as a viable therapeutic strategy to preserve bone homeostasis in elderly and immunocompromised patients.

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“…BMP-2 played a key role in bone regeneration. Studies have proven that overexpression of leucine-rich repeat-containing G-protein coupled receptor 5 (LGR5) can activate the Wnt/β-catenin pathway and thereby enhance the osteogenic differentiation of MC3T3-E1 cells . The study of Li et al suggested that MFAP5 could regulate the osteogenic differentiation of BMSCs through the Wnt/β-catenin signaling pathway.…”

Section: Discussionmentioning

confidence: 99%

“…Studies have proven that overexpression of leucine-rich repeat-containing G-protein coupled receptor 5 (LGR5) can activate the Wnt/β-catenin pathway and thereby enhance the osteogenic differentiation of MC3T3-E1 cells. 50 The study of Li et al 51 suggested that MFAP5 could regulate the osteogenic differentiation of BMSCs through the Wnt/β-catenin signaling pathway. It was claimed by Yang et al 52 that amyloid β peptide (Aβ) enhanced the osteogenic differentiation of human BMSCs and upregulated the expression of RUNX2 and OC through the Wnt/ β-catenin signaling pathway.…”

Section: Discussionmentioning

confidence: 99%

Biomimetic Porous Magnesium Alloy Scaffolds Promote the Repair of Osteoporotic Bone Defects in Rats through Activating the Wnt/β-Catenin Signaling Pathway

Zhu

Jia

Yang

et al. 2023

ACS Biomater. Sci. Eng.

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In this study, biomimetic porous magnesium alloy scaffolds were prepared to repair femoral bone defects in ovariectomized osteoporotic rats. The purpose of the study was to investigate the effect of biomimetic porous magnesium alloy scaffolds on repairing osteoporotic bone defects and possible mechanisms. The animal model of osteoporosis was established in female SD rats. Three months later, a bone defect of 3 mm in diameter and 3 mm in depth was created in the lateral condyle of the right femur. The rats were then randomly divided into two groups: an experimental group and a control group. Four weeks after surgery, gross specimens were observed and micro-CT scans were performed. The repair of osteoporotic femoral defects in rats was studied histologically using HE staining, Masson staining, and Goldner staining. The expression of Wnt5a, β-catenin, and BMP-2 was measured between groups by immunohistochemical staining. The bone defect was repaired better after the application of biomimetic porous magnesium alloy scaffolds. Immunohistochemical results showed significantly higher expression of Wnt5a, β-catenin, and BMP-2. To conclude, the biomimetic porous magnesium alloy scaffolds proposed in this paper might promote the repair of osteoporotic femoral bone defects in rats possibly through activating the Wnt/β-catenin signaling pathway.

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LGR5 enhances the osteoblastic differentiation of MC3T3‑E1 cells through the Wnt/β‑catenin pathway

Cited by 6 publications

References 37 publications

Metformin activates Wnt/β-catenin for the treatment of diabetic osteoporosis

Metformin activates Wnt/β-catenin for the treatment of diabetic osteoporosis

Effect of nicotinamide mononucleotide on osteogenesis in MC3T3-E1 cells against inflammation-induced by lipopolysaccharide

Biomimetic Porous Magnesium Alloy Scaffolds Promote the Repair of Osteoporotic Bone Defects in Rats through Activating the Wnt/β-Catenin Signaling Pathway

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