Fenofibrate induces PPARα and BMP2 expression to stimulate osteoblast differentiation

Kim, Yu-Ha; Jang, Won‐Gu; Oh, So-Young; Kim, Jung-Woo; Lee, Mi Nam; Song, Jeong Hwa; Yang, Jin-Woo; Zang, Yaran; Koh, Jeong‐Tae

doi:10.1016/j.bbrc.2019.10.048

Cited by 37 publications

(22 citation statements)

References 24 publications

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“…Fenofibrate is a PPARα agonist used for lipid-lowering to reduce the levels of cholesterol. It has been shown that fenofibrate promotes osteoblast differentiation by increasing the expression of BMP2 in MC3T3-E1 cells [ 25 ]. Consistently, the cholesterol-lowering agent lovastatin has been reported to increase osteogenic differentiation [ 26 ].…”

Section: Discussionmentioning

confidence: 99%

Geniposide Ameliorated Dexamethasone-Induced Cholesterol Accumulation in Osteoblasts by Mediating the GLP-1R/ABCA1 Axis

Zheng

Xiao

Zhang

et al. 2021

Cells

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Background: Overexposure to glucocorticoid (GC) produces various clinical complications, including osteoporosis (OP), dyslipidemia, and hypercholesterolemia. Geniposide (GEN) is a natural iridoid compound isolated from Eucommia ulmoides. Our previous study found that GEN could alleviate dexamethasone (DEX)-induced differentiation inhibition of MC3T3-E1 cells. However, whether GEN protected against Dex-induced cholesterol accumulation in osteoblasts was still unclear. Methods: DEX was used to induce rat OP. Micro-CT data was obtained. The ALP activity and mineralization were determined by the staining assays, and the total intracellular cholesterol was determined by the ELISA kits. The protein expression was detected by western blot. Results: GEN ameliorated Dex-induced micro-structure damages and cell differentiation inhibition in the bone trabecula in rats. In MC3T3-E1 cells, Dex enhanced the total intracellular cholesterol, which reduced the activity of cell proliferation and differentiation. Effectively, GEN decreased DEX-induced cholesterol accumulation, enhanced cell differentiation, and upregulated the expression of the GLP-1R/ABCA1 axis. In addition, inhibition of ABAC1 expression reversed the actions of GEN. Treatment with Exendin9-39, a GLP-1R inhibitor, could abrogate the protective activity of GEN. Conclusions: GEN ameliorated Dex-induced accumulation of cholesterol and inhibition of cell differentiation by mediating the GLP-1R/ABCA1 axis in MC3T3-E1 cells.

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Section: Discussionmentioning

confidence: 99%

Geniposide Ameliorated Dexamethasone-Induced Cholesterol Accumulation in Osteoblasts by Mediating the GLP-1R/ABCA1 Axis

Zheng

Xiao

Zhang

et al. 2021

Cells

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“…To reduce the stress response, hepatic stellate cells initiate an unfolded protein response by limiting the accumulation of unfolded proteins during transient stress, which promotes cell activation and accelerates the development of LF. Peroxisome proliferation-activated receptor (PPAR) belongs to the nuclear hormone receptor family and plays an important role in many biological processes, such as adipogenesis ( Lefterova et al, 2014 ), cell differentiation ( Kim et al, 2019 ), cell growth regulation ( Zhang X. et al, 2019 ) and inflammation ( Bougarne et al, 2018 ). Previous studies have found that the activation of the PPAR pathway can delay the progression of hepatic fibrosis, and its activation can inhibit the transformation of HSCs from a resting state to an activated state ( Guo et al, 2005 ; Anty and Lemoine, 2011 ).…”

Section: Discussionmentioning

confidence: 99%

Comprehensive Analysis of the Transcriptome-Wide m6A Methylation Modification Difference in Liver Fibrosis Mice by High-Throughput m6A Sequencing

Chang

Chen

et al. 2021

Front. Cell Dev. Biol.

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N6-Methyladenosine (m6A), a unique and common mRNA modification method in eukaryotes, is involved in the occurrence and development of many diseases. Liver fibrosis (LF) is a common response to chronic liver injury and may lead to cirrhosis and even liver cancer. However, the involvement of m6A methylation in the development of LF is still unknown. In this study, we performed a systematic evaluation of hepatic genome-wide m6A modification and mRNA expression by m6A-seq and RNA-seq using LF mice. There were 3,315 genes with significant differential m6A levels, of which 2,498 were hypermethylated and 817 hypomethylated. GO and KEGG analyses illustrated that differentially expressed m6A genes were closely correlated with processes such as the endoplasmic reticulum stress response, PPAR signaling pathway and TGF-β signaling pathway. Moreover, a total of 90 genes had both a significant change in the m6A level and mRNA expression shown by joint analysis of m6A-seq and RNA-seq. Hence, the critical elements of m6A modification, including methyltransferase WTAP, demethylases ALKBH5 and binding proteins YTHDF1 were confirmed by RT-qPCR and Western blot. In an additional cell experiment, we also observed that the decreased expression of WTAP induced the development of LF as a result of promoting hepatic stellate cell (HSC) activation. Therefore, this study revealed unique differential m6A methylation patterns in LF mice and suggested that m6A methylation was associated with the occurrence and course of LF to some extent.

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“…When PPAR γ expression was ablated in mature osteoblasts and osteocytes, the mutant mice exhibited increased femoral bone mineral density and trabecular bone volume as well as reduced fat mass and higher energy expenditure [ 92 ]. In contrast, pharmacological induction of PPAR α expression concomitantly enhanced expression of bone morphogenetic protein 2 (BMP-2) and calcium deposition [ 93 ]. We identified accumulation of ApoA2 and ApoC3 (5.14 and 2.18-fold increase, respectively) working downstream of PPAR α pathway in osteoblasts, the former additionally validated by immunocytochemistry ( Figure 3 ).…”

Section: Resultsmentioning

confidence: 99%

Comparative Proteomic and Metabolomic Analysis of Human Osteoblasts, Differentiated from Dental Pulp Stem Cells, Hinted Crucial Signaling Pathways Promoting Osteogenesis

Nováková

Danchenko

Okajčeková

et al. 2021

IJMS

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Population aging has been a global trend for the last decades, which increases the pressure to develop new cell-based or drug-based therapies, including those that may cure bone diseases. To understand molecular processes that underlie bone development and turnover, we followed osteogenic differentiation of human dental pulp stem cells (DPSCs) using a specific induction medium. The differentiation process imitating in vivo osteogenesis is triggered by various signaling pathways and is associated with massive proteome and metabolome changes. Proteome was profiled by ultrahigh-performance liquid chromatography and comprehensively quantified by ion mobility-enhanced mass spectrometry. From 2667 reproducibly quantified proteins, 432 were differentially abundant by strict statistic criteria. Metabolome profiling was carried out by nuclear magnetic resonance. From 27 detected metabolites, 8 were differentially accumulated. KEGG and MetaboAnalyst hinted metabolic pathways that may be involved in the osteogenic process. Enrichment analysis of differentially abundant proteins highlighted PPAR, FoxO, JAK-STAT, IL-17 signaling pathways, biosynthesis of thyroid hormones and steroids, mineral absorption, and fatty acid metabolism as processes with prominent impact on osteoinduction. In parallel, metabolomic data showed that aminoacyl-tRNA biosynthesis, as well as specific amino acids, likely promote osteodifferentiation. Targeted immunoassays validated and complemented omic results. Our data underlined the complexity of the osteogenic mechanism. Finally, we proposed promising targets for future validation in patient samples, a step toward the treatment of bone defects.

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Fenofibrate induces PPARα and BMP2 expression to stimulate osteoblast differentiation

Cited by 37 publications

References 24 publications

Geniposide Ameliorated Dexamethasone-Induced Cholesterol Accumulation in Osteoblasts by Mediating the GLP-1R/ABCA1 Axis

Geniposide Ameliorated Dexamethasone-Induced Cholesterol Accumulation in Osteoblasts by Mediating the GLP-1R/ABCA1 Axis

Comprehensive Analysis of the Transcriptome-Wide m6A Methylation Modification Difference in Liver Fibrosis Mice by High-Throughput m6A Sequencing

Comparative Proteomic and Metabolomic Analysis of Human Osteoblasts, Differentiated from Dental Pulp Stem Cells, Hinted Crucial Signaling Pathways Promoting Osteogenesis

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