IL-6 potentiates BMP-2-induced osteogenesis and adipogenesis via two different BMPR1A-mediated pathways

Huang, Ru‐Lin; Sun, Yangbai; Ho, Chia-Kang; Liu, Kai; Tang, Qi‐Qun; Xie, Yun; Li, Qingfeng

doi:10.1038/s41419-017-0126-0

Cited by 45 publications

(48 citation statements)

References 43 publications

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“…Another finding of this study is that the expression of the SASP protein, IL‐6, which is also a pro‐inflammatory cytokine, was markedly upregulated in IGFBP7‐treated fibroblasts. Importantly, IL‐6 and its receptor, IL‐6R, are elevated in bone‐derived mesenchymal stem cells, and IL‐6 signaling activates STAT3 phosphorylation and downstream signaling to induce osteogenic gene expression . Our study showed that neutralization of secreted IL‐6 abrogated fibroblast to osteoblast reprogramming, suggesting a key role of autocrine IL‐6 signaling in IGFBP‐mediated osteoblastic reprogramming.…”

Section: Discussionmentioning

confidence: 62%

“…Importantly, IL-6 and its receptor, IL-6R, are elevated in bone-derived mesenchymal stem cells, and IL-6 signaling activates STAT3 phosphorylation and downstream signaling to induce osteogenic gene expression. 54,55 Our study showed that neutralization of secreted IL-6 abrogated fibroblast to osteoblast reprogramming, suggesting a key role of autocrine IL-6 signaling in IGFBP-mediated osteoblastic reprogramming. However, other mechanisms might also be worthy of investigation.…”

Section: Discussionmentioning

confidence: 74%

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Reprogramming of human fibroblasts into osteoblasts by insulin-like growth factor-binding protein 7

Chiu

Lee

et al. 2020

Stem Cells Translational Medicine

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The induced pluripotent stem cell (iPSC) is a promising cell source for tissue regeneration. However, the therapeutic value of iPSC technology is limited due to the complexity of induction protocols and potential risks of teratoma formation. A trans‐differentiation approach employing natural factors may allow better control over reprogramming and improved safety. We report here a novel approach to drive trans‐differentiation of human fibroblasts into functional osteoblasts using insulin‐like growth factor binding protein 7 (IGFBP7). We initially determined that media conditioned by human osteoblasts can induce reprogramming of human fibroblasts to functional osteoblasts. Proteomic analysis identified IGFBP7 as being significantly elevated in media conditioned with osteoblasts compared with those with fibroblasts. Recombinant IGFBP7 induced a phenotypic switch from fibroblasts to osteoblasts. The switch was associated with senescence and dependent on autocrine IL‐6 signaling. Our study supports a novel strategy for regenerating bone by using IGFBP7 to trans‐differentiate fibroblasts to osteoblasts.

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Section: Discussionmentioning

confidence: 62%

Section: Discussionmentioning

confidence: 74%

Reprogramming of human fibroblasts into osteoblasts by insulin-like growth factor-binding protein 7

Chiu

Lee

et al. 2020

Stem Cells Translational Medicine

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“…The BMP pathway is involved in numerous physiological and pathological processes [77]. BMPs control MSC regulation, such as lineage specification of adipocytes which are one of the major elements of the mammary gland microenvironment [78][79][80]. Alterations in BMP signaling have been implicated in metabolic disorders such as obesity in women [81,82].…”

Section: Bmp and Mammary Epithelial Stem Cellsmentioning

confidence: 99%

A Potential New Mechanism for Bisphenol Molecules to Initiate Breast Cancer through Alteration of Bone Morphogenetic Protein Signaling in Stem Cells and Their Microenvironment

Guyot¹,

Maguer-Satta²

2020

Breast Cancer Biology

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Endocrine disruptors interfere with endocrine-mediated regulations of cell or organ functions. Estrogens are one of the main hormones altered by endocrine disruptors like bisphenol A (BPA). Stem cells are active from embryogenesis to late stages of adult life. Their unique properties, such as an extended lifespan and low cycling features, render these cell privileged targets of long-term exposure to numerous factors. Therefore, stem cells are likely to be affected following exposure to endocrine disruptors. One of the major signaling pathways involved in stem cell regulation is the bone morphogenetic protein (BMP) pathway. The BMP pathway is known for its involvement in numerous physiological and pathophysiological processes. Exposure of human mammary stem cells to pollutants such as BPA initiates fundamental changes in stem cells, in particular by altering major elements of BMP signaling, such as receptor expression and localization. Lastly, BPA and its substitute bisphenol S (BPS) have similar impacts on BMP signaling despite their different ER-binding properties, supporting the hypothesis that their biological effects cannot be extrapolated only from their interaction with ERα66. We review recent discoveries in this field and discuss their implications for cancer diagnosis, prevention, and treatment, as well as their relevance for studies on endocrine disruptors.

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“…Then, when the cultured cell fusion degree reached between 60% and 70%, the cells were carefully sucked out in order the complete the culture medium, and 2 ml of osteogenic differentiation culture medium were added. The induced differentiation was stained on the 21st day [19,20] .…”

Section: Msc Differentiationsmentioning

confidence: 99%

“…During the maintenance of Solution B, fresh Solution B was used every three days. Then, the specimens were stained using oil red O [20,21] .…”

Section: Msc Differentiationsmentioning

confidence: 99%

The Effects of METTL3-Mediated Regulations of the Adipogenic Differentiations of Bone Marrow MSCs Targeting PI3K/AKT Pathways on the Chemo-Resistance of AML

Pan¹,

Wang²,

Hou³

et al. 2020

Preprint

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Background: The adipogenic differentiations of bone marrow mesenchymal stem cells (MSCs) result in the promotion of the chemo-resistance of AML cells. When compared with bone marrow MSCs from healthy donors (HD-MSCs), it has been observed that the MSCs from AML (AML-MSCs) displayed enhanced adipogenic differentiation abilities. However, the underlying mechanism remains elusive. METTL3-mediated modifications of m6A mRNA play key roles in the regulation of stem cell differentiation. Unfortunately, there has been no research to date which has reported the fact that the increases of adipogenic differentiation of AML-MSCs are regulated by the m6A. The goal of this study was to investigate the critical role of METTL3 in the adipogenesis of AML-MSCs for promoting the chemo-resistance of AML.Methods: This study detected the m6A levels of the MSCs total RNA, and then investigated METTL3 functions in the adipogenic differentiations of MSCs using knockdown and overexpression experimental methods. The effects of the adipogenic differentiations of HD-MSCs/AML-MSCs on the chemo-resistance to AML were also examined. In addition, the gene transcriptome and m6A epigenetic changes of AML-MSCs from four AML patients, and the HD-MSCs from three healthy donors, were analyzed in this study. The differentially expressed genes and pathways were successfully identified, and clinical specimens were used to adjust gene expressions in order to determine their effects on the adipogenic differentiations of MSC.Results: The results demonstrated that METTL3 could significantly inhibit the adipogenic differentiations of MSCs. It was found that when compared with the HD-MSCs, the expressions of the PI3K/AKT signaling pathways in the AML-MSCs were significantly increased. Meanwhile, the levels of m6A were significantly decreased. Therefore, it was indicated that by blocking the PI3K/AKT signaling pathways with AKT inhibitors, the adipogenic differentiations of the MSCs could be significantly inhibited. Moreover, the increased adipogenic differentiations induced by the METTL3 could significantly increase the chemo-resistance of the AML.Conclusions: It was found that the METTL3 had enhanced the modification levels of m6A in the PI3K/AKT signaling pathways, and then reduced its expression. Subsequently, the adipogenic differentiations were inhibited. Then, the bone marrow microenvironments, as well as chemo-resistance of the AML, were successfully changed.

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IL-6 potentiates BMP-2-induced osteogenesis and adipogenesis via two different BMPR1A-mediated pathways

Cited by 45 publications

References 43 publications

Reprogramming of human fibroblasts into osteoblasts by insulin-like growth factor-binding protein 7

Reprogramming of human fibroblasts into osteoblasts by insulin-like growth factor-binding protein 7

A Potential New Mechanism for Bisphenol Molecules to Initiate Breast Cancer through Alteration of Bone Morphogenetic Protein Signaling in Stem Cells and Their Microenvironment

The Effects of METTL3-Mediated Regulations of the Adipogenic Differentiations of Bone Marrow MSCs Targeting PI3K/AKT Pathways on the Chemo-Resistance of AML

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