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Resveratrol Promotes Osteogenic Differentiation of Bone Marrow-Derived Mesenchymal Stem Cells Through miR-193a/SIRT7 Axis

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Abstract

Resveratrol (RES) is a novel dietary phenol compound derived from plants and has been studied extensively for its health benefit and medical potential including osteoporosis. The purpose of this study is to investigate the role of resveratrol in osteoporosis in vivo and in vitro and explore the mechanism of osteogenic differentiation of BMSCs. RT-qPCR, ELISA, and Western blot were used to measure the expression level of miR-193a, SIRT7, and osteogenic markers proteins. The interaction between miR-193a and SIRT7 was validated by dual-luciferase reporter assay. Moreover, MTT assay was conducted to detect cell viability. Alizarin red s staining was used to examine bone formation and calcium deposits. The ovariectomized rat model was set up successfully and HE staining was used to examine femoral trabeculae tissue. Our results showed that miR-193a was overexpressed, while SIRT7 was downregulated in osteoporosis. RES suppressed miR-193a to promote osteogenic differentiation. Mechanically, miR-193a targeted and negative regulated SIRT7. Additionally, it was confirmed that SIRT7 promoted osteogenic differentiation of BMSCs through NF-κB signaling pathway. Further study indicated that RES exerted its beneficial function through miR-193a/SIRT7-mediated NF-κB signaling to alleviate osteoporosis in vivo. Our research suggested that the RES-modulated miR-193a inhibition is responsible for the activation of SIRT7/NF-κB signaling pathway in the process of osteogenic differentiation, providing a novel insight into diagnosis and treatment of osteoporosis.

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Data Availability

The datasets used or analyzed during the current study are available from the corresponding author on reasonable request.

Code Availability

Not applicable.

Abbreviations

ALP:

Alkaline phosphatase

BMSCs:

Bone marrow-derived mesenchymal stem cells

BMP2:

Bone morphogenetic protein 2

miR-193a:

MicroRNA-193a

NC:

Negative control

NF-κB:

Nuclear factor kappa-light-chain-enhancer of activated B cells

OPN:

Osteopontin

OP:

Osteoporosis patient

RES:

Resveratrol

RT-qPCR:

Reverse transcript quantitative polymerase chain reaction

RUNX2:

Runt-related transcription factor 2

SIRT7:

Sirtuin 7

siRNA:

Small interfering RNA

WB:

Western blotting

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Correspondence to Wen-Ge Liu.

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Disclosure

Chen-Yang Song, Yu Guo, Fen-Yong Chen, Wen-Ge Liu authors have any conflict of interests.

Human and Animal Rights

The protocol has been approved by ethnic committee of Fujian Medical University Union Hospital. All animal experiments were conducted in accordance to institutional guidelines for the care and use of laboratory animals of Fujian Medical University Union Hospital, China and met the regulations published by National Institutes of Health Guide for Care and Use of Laboratory Animals.

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All patients were informed of the study and signed the written consent. The informed consent obtained from study participants.

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Song, CY., Guo, Y., Chen, FY. et al. Resveratrol Promotes Osteogenic Differentiation of Bone Marrow-Derived Mesenchymal Stem Cells Through miR-193a/SIRT7 Axis. Calcif Tissue Int 110, 117–130 (2022). https://doi.org/10.1007/s00223-021-00892-7

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  • DOI: https://doi.org/10.1007/s00223-021-00892-7

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