The role of gut microbiota metabolite trimethylamine N-oxide in functional impairment of bone marrow mesenchymal stem cells in osteoporosis disease

Abstract

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 microbiotaderived 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.

Psoralidin prevents caffeine-induced damage and abnormal differentiation of bone marrow mesenchymal stem cells via the classical estrogen receptor pathway

“…In recent decades, bone marrow mesenchymal stem cells (BMSCs) have emerged as potential microenvironmental modulators (6,7). BMSCs, as a type of non-hematopoietic multipotent stem cell, can be differentiated into various cell types, including osteoblasts, adipocytes, and chondrocytes, under specific conditions (8,9). An increasing number of studies have indicated that OP is mainly attributable to the imbalance between the osteogenesis and adipogenesis of BMSCs (10).…”

Correlation between gut microbiota diversity and psychogenic erectile dysfunction

“…The normal gut microbiota in the human body is mainly composed of firmicutes, Bacteroidetes, proteobacteria, and actinomycetes. According to the impact on human health, gut microbiota can be divided into three categories: symbiotic bacteria, opportunistic bacteria, and pathogenic bacteria, which are dynamically balanced to maintain the homeostasis of the intestinal environment (2). Intestinal beneficial bacteria (i.e., probiotics) include bifidobacteria, lactobacillus, and so on.…”

Effects of Serum Metabolites on the Pancreatic Transcriptome in Acute Acalculous Cholecystitis

“…The TNF gene encodes a multifunctional proinflammatory cytokine involved in the regulation of various biological processes, including cell proliferation, differentiation, apoptosis, lipid metabolism, and blood coagulation. It has been proven that TMAO can promote the production of the proinflammatory cytokines IL-1 β , IL-6, and TNF- α in vitro [ 39 , 40 ], and the activation of the NF- κ B pathway is necessary for TMAO to induce bone marrow mesenchymal stem cells to produce proinflammatory cytokines and release active oxygen [ 40 ]. TNF was determined to be closely related to acute pancreatitis.…”