IFN-γ-primed human bone marrow mesenchymal stem cells induce tumor cell apoptosis in vitro via tumor necrosis factor-related apoptosis-inducing ligand

Bone marrow mesenchymal stem cells (BMSCs) have the potential for multi-directional differentiation. Tumor necrosis factor-α (TNF-α) plays a role in many diseases. However, the role of TNF-α in the differentiation of BMSCs into osteoblasts remains unclear. Rat-derived BMSCs were divided into normal control group and TNF-α group (5 ng/ml or 10 ng/ml) followed by analysis of BMSCs proliferation by MTT, Caspase3 activity, TNF-α mRNA and serum secretion by Real time PCR and ELISA, ALP activity, Runx2, OP and OC level by Real time PCR and PI3K/AKT signaling protein expression by Western blot. TNF-α significantly promoted the expression of TNF-α mRNA and serum secretion, inhibited cell proliferation, increased Caspase3 and ALP activity, decreased Runx2 and OP expression, and inhibited AKT phosphorylation compared to control (P < 0.05). The inhibition of osteogenic differentiation of BMSCs was more obvious with the increase of TNF-α concentration. TNF-α can inhibit the proliferation of BMSCs, promote apoptosis and inhibit BMSCs osteogenic differentiation via inhibiting the PI3K/AKT pathway.

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Migration of bone marrow-derived mesenchymal stem cells induced by tumor necrosis factor-α and its possible role in wound healing

Wound Repair and Regeneration ◽

10.1111/j.1524-475x.2009.00454.x ◽

2009 ◽

Vol 17 (2) ◽

pp. 185-191 ◽

Cited By ~ 76

Author(s):

Xiaobing Fu ◽

Bing Han ◽

Sa Cai ◽

Yonghong Lei ◽

Tongzhu Sun ◽

...

Keyword(s):

Stem Cells ◽

Bone Marrow ◽

Wound Healing ◽

Mesenchymal Stem Cells ◽

Tumor Necrosis Factor ◽

Tumor Necrosis ◽

Tumor Necrosis Factor Α ◽

Factor Α ◽

Necrosis Factor

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The let-7f-5p–Nme4 pathway mediates tumor necrosis factor α-induced impairment in osteogenesis of bone marrow-derived mesenchymal stem cells

Biochemistry and Cell Biology ◽

10.1139/bcb-2020-0281 ◽

2021 ◽

pp. 1-11

Author(s):

Ying-Jie Zhao ◽

Zheng-Chao Gao ◽

Xi-Jing He ◽

Jing Li

Keyword(s):

Stem Cells ◽

Bone Marrow ◽

Mesenchymal Stem Cells ◽

Tumor Necrosis Factor ◽

Osteogenic Differentiation ◽

Tumor Necrosis ◽

Tumor Necrosis Factor Α ◽

Tnf Α ◽

Factor Α ◽

Necrosis Factor

Although tumor necrosis factor α (TNF-α)-mediated inflammation significantly impacts osteoporosis, the mechanisms underlying the osteogenic differentiation defects of bone marrow-derived mesenchymal stem cells (BM-MSCs) caused by TNF-α remain poorly understood. We found that TNF-α stimulation of murine BM-MSCs significantly upregulated the expression levels of several microRNAs (miRNAs), including let-7f-5p, but this increase was significantly reversed by treatment with the kinase inhibitor BAY 11-7082. To study gain- or loss of function, we transfected cells with an miRNA inhibitor or miRNA mimic. We then demonstrated that let-7f-5p impaired osteogenic differentiation of BM-MSCs in the absence and presence of TNF-α, as evidenced by alkaline phosphatase and alizarin red staining as well as quantitative assays of the mRNA levels of bone formation marker genes in differentiated BM-MSCs. Moreover, let-7f-5p targets the 3′ untranslated region of Nucleoside diphosphate kinase 4 (Nme4) mRNA and negatively regulates Nme4 expression in mouse BM-MSCs. Ectopic expression of Nme4 completely reversed the inhibitory effects of the let-7f-5p mimic on osteogenic differentiation of mouse BM-MSCs. Furthermore, inhibition of let-7f-5p or overexpression of Nme4 in BM-MSCs restored in-vivo bone formation in an ovariectomized animal model. Collectively, our work indicates that let-7f-5p is involved in TNF-α-mediated reduction of BM-MSC osteogenesis via targeting Nme4.

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