17β-estradiol promotes osteogenic differentiation of BMSCs by regulating mitophagy through ARC

Abstract The study aims to elucidate the mechanism through which 17β-estradiol facilitates osteogenic differentiation in bone marrow mesenchymal stem cells (BMSCs). In our study, lentiviral transfection was employed to establish apoptosis repressor with caspase recruitment domain (ARC) knockdown or...

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Main Authors: Jingcun Shi, Jin Wen, Longwei Hu
Format: Article
Language:English
Published: BMC 2025-01-01
Series:Journal of Orthopaedic Surgery and Research
Subjects:
Online Access:https://doi.org/10.1186/s13018-024-05400-9
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author Jingcun Shi
Jin Wen
Longwei Hu
author_facet Jingcun Shi
Jin Wen
Longwei Hu
author_sort Jingcun Shi
collection DOAJ
description Abstract The study aims to elucidate the mechanism through which 17β-estradiol facilitates osteogenic differentiation in bone marrow mesenchymal stem cells (BMSCs). In our study, lentiviral transfection was employed to establish apoptosis repressor with caspase recruitment domain (ARC) knockdown or overexpression in BMSCs. The impact of 17β-estradiol on ARC expression was assessed using western blot, RT-PCR and immunofluorescence. Techniques such as ALP staining, ALP activity assay, western blot, RT-PCR and immunofluorescence staining were utilized to examine the influence of ARC expression levels on the osteogenic differentiation of BMSCs and the osteoclastic differentiation of Raw264.7 cell lines. Mitophagy flux levels in BMSCs were detected using the mitophagy detection kit. RNA sequencing and bioinformatics analyses were conducted to explore potential mechanisms of ARC regulation in BMSCs osteogenic differentiation. To sum up, 17β-estradiol can modulate bone homeostasis by adjusting ARC expression. ARC stimulates mitophagy in BMSCs via MAPK/Akt pathway, identifying ARC as a promising therapeutic target for postmenopausal osteoporosis (PMOP) treatment.
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institution Kabale University
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publishDate 2025-01-01
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series Journal of Orthopaedic Surgery and Research
spelling doaj-art-59cdbc97c1d845df919e16f6bf01c4192025-01-12T12:32:26ZengBMCJournal of Orthopaedic Surgery and Research1749-799X2025-01-0120111210.1186/s13018-024-05400-917β-estradiol promotes osteogenic differentiation of BMSCs by regulating mitophagy through ARCJingcun Shi0Jin Wen1Longwei Hu2Department of Oral and Maxillofacial Surgery – Head & Neck Oncology, Shanghai Ninth People’s Hospital, College of Stomatology, Shanghai Jiao Tong University School of MedicineDepartment of Prosthodontics, Shanghai Ninth People’s Hospital, College of Stomatology, Shanghai Jiao Tong University School of MedicineDepartment of Oral and Maxillofacial Surgery – Head & Neck Oncology, Shanghai Ninth People’s Hospital, College of Stomatology, Shanghai Jiao Tong University School of MedicineAbstract The study aims to elucidate the mechanism through which 17β-estradiol facilitates osteogenic differentiation in bone marrow mesenchymal stem cells (BMSCs). In our study, lentiviral transfection was employed to establish apoptosis repressor with caspase recruitment domain (ARC) knockdown or overexpression in BMSCs. The impact of 17β-estradiol on ARC expression was assessed using western blot, RT-PCR and immunofluorescence. Techniques such as ALP staining, ALP activity assay, western blot, RT-PCR and immunofluorescence staining were utilized to examine the influence of ARC expression levels on the osteogenic differentiation of BMSCs and the osteoclastic differentiation of Raw264.7 cell lines. Mitophagy flux levels in BMSCs were detected using the mitophagy detection kit. RNA sequencing and bioinformatics analyses were conducted to explore potential mechanisms of ARC regulation in BMSCs osteogenic differentiation. To sum up, 17β-estradiol can modulate bone homeostasis by adjusting ARC expression. ARC stimulates mitophagy in BMSCs via MAPK/Akt pathway, identifying ARC as a promising therapeutic target for postmenopausal osteoporosis (PMOP) treatment.https://doi.org/10.1186/s13018-024-05400-917β-estradiolARCBMSCsOsteogenic differentiationMitophagyMAPK
spellingShingle Jingcun Shi
Jin Wen
Longwei Hu
17β-estradiol promotes osteogenic differentiation of BMSCs by regulating mitophagy through ARC
Journal of Orthopaedic Surgery and Research
17β-estradiol
ARC
BMSCs
Osteogenic differentiation
Mitophagy
MAPK
title 17β-estradiol promotes osteogenic differentiation of BMSCs by regulating mitophagy through ARC
title_full 17β-estradiol promotes osteogenic differentiation of BMSCs by regulating mitophagy through ARC
title_fullStr 17β-estradiol promotes osteogenic differentiation of BMSCs by regulating mitophagy through ARC
title_full_unstemmed 17β-estradiol promotes osteogenic differentiation of BMSCs by regulating mitophagy through ARC
title_short 17β-estradiol promotes osteogenic differentiation of BMSCs by regulating mitophagy through ARC
title_sort 17β estradiol promotes osteogenic differentiation of bmscs by regulating mitophagy through arc
topic 17β-estradiol
ARC
BMSCs
Osteogenic differentiation
Mitophagy
MAPK
url https://doi.org/10.1186/s13018-024-05400-9
work_keys_str_mv AT jingcunshi 17bestradiolpromotesosteogenicdifferentiationofbmscsbyregulatingmitophagythrougharc
AT jinwen 17bestradiolpromotesosteogenicdifferentiationofbmscsbyregulatingmitophagythrougharc
AT longweihu 17bestradiolpromotesosteogenicdifferentiationofbmscsbyregulatingmitophagythrougharc