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The role of gut microbiota metabolite trimethylamine N-oxide in functional impairment of bone marrow mesenchymal stem cells in osteoporosis disease
BACKGROUND: Osteoporosis (OP) is a prevalent metabolic bone disease characterized by bone loss and structural deterioration, which increases the risk of fracture especially in older people. Recent research has shown that gut microbes play an important role in OP. Trimethylamine N-oxide (TMAO), a gut...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
AME Publishing Company
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7475507/ https://www.ncbi.nlm.nih.gov/pubmed/32953809 http://dx.doi.org/10.21037/atm-20-5307 |
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author | Lin, Hao Liu, Tianfeng Li, Xiao Gao, Xiang Wu, Tingrui Li, Peng |
author_facet | Lin, Hao Liu, Tianfeng Li, Xiao Gao, Xiang Wu, Tingrui Li, Peng |
author_sort | Lin, Hao |
collection | PubMed |
description | BACKGROUND: Osteoporosis (OP) is a prevalent metabolic bone disease characterized by bone loss and structural deterioration, which increases the risk of fracture especially in older people. Recent research has shown that gut microbes play an important role in OP. Trimethylamine N-oxide (TMAO), a gut microbiota-derived metabolite, has been implicated in the pathogenesis of diseases, including Alzheimer’s and cerebrovascular disease. This study aimed to examine the effect of TMAO in OP. METHODS: In this study, we firstly investigated the relationship between TMAO and OP. Serum samples were collected from patients with OP (n=10), and healthy participants (n=10), and the TMAO level in the serum was detected by ELISA assay. Then, bone marrow mesenchymal stem cells (BMSCs) were treated with TMAO, and we observed its effect on adipogenic and osteogenic differentiation, cell proliferation, reactive oxygen species (ROS) release, and inflammatory cytokine[interleukin (IL)-1β, IL-6 and tumor necrosis factor-alpha (TNF-α)] levels. Finally, we illustrated the underlying mechanism through which TMAO influenced BMSCs functions. RESULTS: Compared to the healthy group, highly significant TMAO levels were observed in the serum of the OP patients. When studied in vitro, TMAO treatment significantly promoted BMSCs adipogenesis and attenuated osteogenesis, increased ROS release and pro-inflammatory cytokine IL-1β, IL-6 and TNF-α production, and inhibited cell proliferation. Furthermore, we found that activation of the nuclear factor-κB (NF-κB) signaling pathway was necessary for TMAO to induce pro-inflammatory cytokine production, ROS release, and adipogenic and osteogenic differentiation in BMSCs. CONCLUSIONS: Elevated TMAO levels have a strong negative correlation with the degree of bone mineral density (BMD) in OP. TMAO regulates BMSCs cell function by activating the NF-κB signaling pathway, which affects the balance of bone metabolism, leading to acceleration of bone loss and further progression of OP. |
format | Online Article Text |
id | pubmed-7475507 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | AME Publishing Company |
record_format | MEDLINE/PubMed |
spelling | pubmed-74755072020-09-17 The role of gut microbiota metabolite trimethylamine N-oxide in functional impairment of bone marrow mesenchymal stem cells in osteoporosis disease Lin, Hao Liu, Tianfeng Li, Xiao Gao, Xiang Wu, Tingrui Li, Peng Ann Transl Med Original Article BACKGROUND: Osteoporosis (OP) is a prevalent metabolic bone disease characterized by bone loss and structural deterioration, which increases the risk of fracture especially in older people. Recent research has shown that gut microbes play an important role in OP. Trimethylamine N-oxide (TMAO), a gut microbiota-derived metabolite, has been implicated in the pathogenesis of diseases, including Alzheimer’s and cerebrovascular disease. This study aimed to examine the effect of TMAO in OP. METHODS: In this study, we firstly investigated the relationship between TMAO and OP. Serum samples were collected from patients with OP (n=10), and healthy participants (n=10), and the TMAO level in the serum was detected by ELISA assay. Then, bone marrow mesenchymal stem cells (BMSCs) were treated with TMAO, and we observed its effect on adipogenic and osteogenic differentiation, cell proliferation, reactive oxygen species (ROS) release, and inflammatory cytokine[interleukin (IL)-1β, IL-6 and tumor necrosis factor-alpha (TNF-α)] levels. Finally, we illustrated the underlying mechanism through which TMAO influenced BMSCs functions. RESULTS: Compared to the healthy group, highly significant TMAO levels were observed in the serum of the OP patients. When studied in vitro, TMAO treatment significantly promoted BMSCs adipogenesis and attenuated osteogenesis, increased ROS release and pro-inflammatory cytokine IL-1β, IL-6 and TNF-α production, and inhibited cell proliferation. Furthermore, we found that activation of the nuclear factor-κB (NF-κB) signaling pathway was necessary for TMAO to induce pro-inflammatory cytokine production, ROS release, and adipogenic and osteogenic differentiation in BMSCs. CONCLUSIONS: Elevated TMAO levels have a strong negative correlation with the degree of bone mineral density (BMD) in OP. TMAO regulates BMSCs cell function by activating the NF-κB signaling pathway, which affects the balance of bone metabolism, leading to acceleration of bone loss and further progression of OP. AME Publishing Company 2020-08 /pmc/articles/PMC7475507/ /pubmed/32953809 http://dx.doi.org/10.21037/atm-20-5307 Text en 2020 Annals of Translational Medicine. All rights reserved. https://creativecommons.org/licenses/by-nc-nd/4.0/Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0 (https://creativecommons.org/licenses/by-nc-nd/4.0/) . |
spellingShingle | Original Article Lin, Hao Liu, Tianfeng Li, Xiao Gao, Xiang Wu, Tingrui Li, Peng The role of gut microbiota metabolite trimethylamine N-oxide in functional impairment of bone marrow mesenchymal stem cells in osteoporosis disease |
title | The role of gut microbiota metabolite trimethylamine N-oxide in functional impairment of bone marrow mesenchymal stem cells in osteoporosis disease |
title_full | The role of gut microbiota metabolite trimethylamine N-oxide in functional impairment of bone marrow mesenchymal stem cells in osteoporosis disease |
title_fullStr | The role of gut microbiota metabolite trimethylamine N-oxide in functional impairment of bone marrow mesenchymal stem cells in osteoporosis disease |
title_full_unstemmed | The role of gut microbiota metabolite trimethylamine N-oxide in functional impairment of bone marrow mesenchymal stem cells in osteoporosis disease |
title_short | The role of gut microbiota metabolite trimethylamine N-oxide in functional impairment of bone marrow mesenchymal stem cells in osteoporosis disease |
title_sort | role of gut microbiota metabolite trimethylamine n-oxide in functional impairment of bone marrow mesenchymal stem cells in osteoporosis disease |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7475507/ https://www.ncbi.nlm.nih.gov/pubmed/32953809 http://dx.doi.org/10.21037/atm-20-5307 |
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