Weighted gene correlation network analysis reveals novel biomarkers associated with mesenchymal stromal cell differentiation in early phase

Xiao, Bin; Wang, Guozhu; Li, Weiwei

doi:10.7717/peerj.8907

Cited by 11 publications

(8 citation statements)

References 58 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The rate of bone defects, fracture nonunion, and osteoporosis incidence continues to rise, and available therapeutic options remain limited. These diseases, closely related to the osteogenic differentiation of bone marrow–derived mesenchymal stem cells (BMSCs), have been confirmed by numerous studies ( Marongiu et al, 2020 ; Xiao et al, 2020 ; Xiong et al, 2020 ; Jiang et al, 2021 ).…”

Section: Introductionmentioning

confidence: 82%

Bioinformatics-Guided Analysis Uncovers AOX1 as an Osteogenic Differentiation-Relevant Gene of Human Mesenchymal Stem Cells

Sun

Cheng

et al. 2022

Front. Mol. Biosci.

View full text Add to dashboard Cite

Background: The available therapeutic options of bone defects, fracture nonunion, and osteoporosis remain limited, which are closely related to the osteogenic differentiation of bone marrow–derived mesenchymal stem cells (BMSCs). Thus, there remains an urgent demand to develop a prediction method to infer osteogenic differentiation–related genes in BMSCs.Method: We performed differential expression analysis between hBMSCs and osteogenically induced samples. Association analysis, co-expression analysis, and PPI analysis are then carried out to identify potential osteogenesis-related regulators. GO enrichment analysis and GSEA are performed to identify significantly enriched pathways associated with AOX1. qRT-PCR and Western blotting were employed to investigate the expression of genes on osteogenic differentiation, and plasmid transfection was used to overexpress the gene AOX1 in hBMSCs.Result: We identified 25 upregulated genes and 17 downregulated genes. Association analysis and PPI network analysis among these differentially expressed genes show that AOX1 is a potential regulator of osteogenic differentiation. GO enrichment analysis and GSEA show that AOX1 is significantly associated with osteoblast-related pathways. The experiments revealed that AOX1 level was higher and increased gradually in differentiated BMSCs compared with undifferentiated BMSCs, and AOX1 overexpression significantly increased the expression of osteo-specific genes, thereby clearly indicating that AOX1 plays an important role in osteogenic differentiation. Moreover, our method has ability in discriminating genes with osteogenic differentiation properties and can facilitate the process of discovery of new osteogenic differentiation–related genes.Conclusion: These findings collectively demonstrate that AOX1 is an osteogenic differentiation-relevant gene and provide a novel method established with a good performance for osteogenic differentiation-relevant genes prediction.

show abstract

Section: Introductionmentioning

confidence: 82%

Bioinformatics-Guided Analysis Uncovers AOX1 as an Osteogenic Differentiation-Relevant Gene of Human Mesenchymal Stem Cells

Sun

Cheng

et al. 2022

Front. Mol. Biosci.

View full text Add to dashboard Cite

show abstract

“…Although FOXQ1 was not found to be involved in any OP-and diabetes-related terms or pathways, recent studies showed that its role in osteogenesis or gluconeogenesis is not direct, requiring the involvements of other genes and pathways. For example, FOXQ1 is associated with both adipogenic and osteogenic differentiations of MSCs in an early phase [36]. Overexpression of FOXQ1 promotes the osteogenic differentiation of BMSC via Wnt/β-catenin signaling by binding with ANXA2 [37].…”

Section: Discussionmentioning

confidence: 99%

A gene expression profile for the lower osteogenic potent of bone-derived MSCs from osteoporosis with T2DM and the potential mechanism

Xia

Wang

et al. 2022

J Orthop Surg Res

View full text Add to dashboard Cite

Background Osteoporosis (OP) patients complicated with type II diabetes mellitus (T2DM) has a higher fracture risk than the non-diabetic patients, and mesenchymal stem cells (MSCs) from T2DM patients also show a weaker osteogenic potent. The present study aimed to provide a gene expression profile in MSCs from diabetic OP and investigated the potential mechanism. Methods The bone-derived MSC (BMSC) was isolated from OP patients complicated with or without T2DM (CON-BMSC, T2DM-BMSC). Osteogenic differentiation was evaluated by qPCR analysis of the expression levels of osteogenic markers, ALP activity and mineralization level. The differentially expressed genes (DEGs) in T2DM-BMSC was identified by RNA-sequence, and the biological roles of DEGs was annotated by bioinformatics analyses. The role of silencing the transcription factor (TF), Forkhead box Q1 (FOXQ1), on the osteogenic differentiation of BMSC was also investigated. Results T2DM-BMSC showed a significantly reduced osteogenic potent compare to the CON-BMSC. A total of 448 DEGs was screened in T2DM-BMSC, and bioinformatics analyses showed that many TFs and the target genes were enriched in various OP- and diabetes-related biological processes and pathways. FOXQ1 had the highest verified fold change (abs) among the top 8 TFs, and silence of FOXQ1 inhibited the osteogenic differentiation of CON-BMSC. Conclusions Our study provided a comprehensive gene expression profile of BMSC in diabetic OP, and found that downregulated FOXQ1 was responsible for the reduced osteogenic potent of T2DM-BSMC. This is of great importance for the special mechanism researches and the treatment of diabetic OP.

show abstract

“…As one of the most common complications following severe fracture, bone tumour ablation, and debridement of a variety of bone infections, large bone defects continue to be a challenge for orthopaedic surgeons [ 1 , 2 ]. Numerous studies have demonstrated that the complications linked to large bone defects are closely related to the osteogenic differentiation of bone mesenchymal stem cells (BMSCs) [ 3 – 6 ]. Due to bone graft-associated donor site morbidity , tissue engineering research has investigated BMSCs for several years as one of the body's own mechanisms for bone repair [ 7 , 8 ].…”

Section: Introductionmentioning

confidence: 99%

Knockdown of FOXA1 enhances the osteogenic differentiation of human bone marrow mesenchymal stem cells partly via activation of the ERK1/2 signalling pathway

Wang

et al. 2022

Stem Cell Res Ther

View full text Add to dashboard Cite

Background The available therapeutic options for large bone defects remain extremely limited, requiring new strategies to accelerate bone healing. Genetically modified bone mesenchymal stem cells (BMSCs) with enhanced osteogenic capacity are recognised as one of the most promising treatments for bone defects. Methods We performed differential expression analysis of miRNAs between human BMSCs (hBMSCs) and human dental pulp stem cells (hDPSCs) to identify osteogenic differentiation-related microRNAs (miRNAs). Furthermore, we identified shared osteogenic differentiation-related miRNAs and constructed an miRNA-transcription network. The Forkhead box protein A1 (FOXA1) knockdown strategy with a lentiviral vector was used to explore the role of FOXA1 in the osteogenic differentiation of MSCs. Cell Counting Kit-8 was used to determine the effect of the knockdown of FOXA1 on hBMSC proliferation; real-time quantitative reverse transcription PCR (qRT-PCR) and western blotting were used to investigate target genes and proteins; and alkaline phosphatase (ALP) staining and Alizarin Red staining (ARS) were used to assess ALP activity and mineral deposition, respectively. Finally, a mouse model of femoral defects was established in vivo, and histological evaluation and radiographic analysis were performed to verify the therapeutic effects of FOXA1 knockdown on bone healing. Results We identified 22 shared and differentially expressed miRNAs between hDPSC and hBMSC, 19 of which were downregulated in osteogenically induced samples. The miRNA-transcription factor interaction network showed that FOXA1 is the most significant and novel osteogenic differentiation biomarker among more than 300 transcription factors that is directly targeted by 12 miRNAs. FOXA1 knockdown significantly promoted hBMSC osteo-specific genes and increased mineral deposits in vitro. In addition, p-ERK1/2 levels were upregulated by FOXA1 silencing. Moreover, the increased osteogenic differentiation of FOXA1 knockdown hBMSCs was partially rescued by the addition of ERK1/2 signalling inhibitors. In a mouse model of femoral defects, a sheet of FOXA1-silencing BMSCs improved bone healing, as detected by microcomputed tomography and histological evaluation. Conclusion These findings collectively demonstrate that FOXA1 silencing promotes the osteogenic differentiation of BMSCs via the ERK1/2 signalling pathway, and silencing FOXA1 in vivo effectively promotes bone healing, suggesting that FOXA1 may be a novel target for bone healing.

show abstract

Weighted gene correlation network analysis reveals novel biomarkers associated with mesenchymal stromal cell differentiation in early phase

Abstract: Osteoporosis is a major public health problem that is associated with high morbidity and mortality, and its prevalence is increasing as the world's population ages.

Cited by 11 publications

References 58 publications

Bioinformatics-Guided Analysis Uncovers AOX1 as an Osteogenic Differentiation-Relevant Gene of Human Mesenchymal Stem Cells

Bioinformatics-Guided Analysis Uncovers AOX1 as an Osteogenic Differentiation-Relevant Gene of Human Mesenchymal Stem Cells

A gene expression profile for the lower osteogenic potent of bone-derived MSCs from osteoporosis with T2DM and the potential mechanism

Knockdown of FOXA1 enhances the osteogenic differentiation of human bone marrow mesenchymal stem cells partly via activation of the ERK1/2 signalling pathway

Contact Info

Product

Resources

About