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

Abstract 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...

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Main Authors: Sheng-li Xia, Zi-yuan Ma, Bin Wang, Feng Gao, Sheng-yang Guo, Xu-han Chen
Format: Article
Language:English
Published: BMC 2022-09-01
Series:Journal of Orthopaedic Surgery and Research
Subjects:
Online Access:https://doi.org/10.1186/s13018-022-03291-2
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author Sheng-li Xia
Zi-yuan Ma
Bin Wang
Feng Gao
Sheng-yang Guo
Xu-han Chen
author_facet Sheng-li Xia
Zi-yuan Ma
Bin Wang
Feng Gao
Sheng-yang Guo
Xu-han Chen
author_sort Sheng-li Xia
collection DOAJ
description Abstract 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.
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spelling doaj.art-c414dc51b7364d67b64dae897cea5d0d2022-12-22T04:24:05ZengBMCJournal of Orthopaedic Surgery and Research1749-799X2022-09-0117111210.1186/s13018-022-03291-2A gene expression profile for the lower osteogenic potent of bone-derived MSCs from osteoporosis with T2DM and the potential mechanismSheng-li Xia0Zi-yuan Ma1Bin Wang2Feng Gao3Sheng-yang Guo4Xu-han Chen5Department of Orthopedics, Shanghai University of Medicine and Health Sciences Affiliated Zhoupu HospitalDepartment of Orthopedics, Shanghai University of Medicine and Health Sciences Affiliated Zhoupu HospitalDepartment of Orthopedics, Shanghai University of Medicine and Health Sciences Affiliated Zhoupu HospitalDepartment of Orthopedics, Shanghai University of Medicine and Health Sciences Affiliated Zhoupu HospitalDepartment of Orthopedics, Shanghai University of Medicine and Health Sciences Affiliated Zhoupu HospitalZhoupu Community Health Service CenterAbstract 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.https://doi.org/10.1186/s13018-022-03291-2T2DMOsteoporosisFOXQ1Osteogenic differentiationMesenchymal stem cells
spellingShingle Sheng-li Xia
Zi-yuan Ma
Bin Wang
Feng Gao
Sheng-yang Guo
Xu-han Chen
A gene expression profile for the lower osteogenic potent of bone-derived MSCs from osteoporosis with T2DM and the potential mechanism
Journal of Orthopaedic Surgery and Research
T2DM
Osteoporosis
FOXQ1
Osteogenic differentiation
Mesenchymal stem cells
title A gene expression profile for the lower osteogenic potent of bone-derived MSCs from osteoporosis with T2DM and the potential mechanism
title_full A gene expression profile for the lower osteogenic potent of bone-derived MSCs from osteoporosis with T2DM and the potential mechanism
title_fullStr A gene expression profile for the lower osteogenic potent of bone-derived MSCs from osteoporosis with T2DM and the potential mechanism
title_full_unstemmed A gene expression profile for the lower osteogenic potent of bone-derived MSCs from osteoporosis with T2DM and the potential mechanism
title_short A gene expression profile for the lower osteogenic potent of bone-derived MSCs from osteoporosis with T2DM and the potential mechanism
title_sort gene expression profile for the lower osteogenic potent of bone derived mscs from osteoporosis with t2dm and the potential mechanism
topic T2DM
Osteoporosis
FOXQ1
Osteogenic differentiation
Mesenchymal stem cells
url https://doi.org/10.1186/s13018-022-03291-2
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