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Upregulated miR-9-5p inhibits osteogenic differentiation of bone marrow mesenchymal stem cells under high glucose treatment

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Journal of Bone and Mineral Metabolism Aims and scope Submit manuscript

Abstract

Introduction

Diabetic osteoporosis (DOP) is a chronic diabetic complication, which is attributed to high glucose (HG)-induced dysfunction of bone marrow mesenchymal stem cells (BMSCs). Studies have revealed that microRNAs (miRNAs) play critical roles in osteogenic differentiation of BMSCs in DOP. Here, the role of miR-9-5p in DOP progression was explored.

Materials and methods

The rat model of DOP was established by intraperitoneal injection of streptozotocin (STZ). BMSCs were treated with high glucose (HG) to establish in vitro models. Gene expression in BMSCs and bone tissues of rats was tested by RT-qPCR. The degree of osteogenic differentiation of BMSCs was examined by Alizarin Red staining and ALP activity analysis. The protein levels of collagen-I (COL1), osteocalcin (OCN), osteopontin (OPN), runt-related transcription factor-2 (RUNX2), and DEAD-Box Helicase 17 (DDX17) in BMSCs were evaluated by western blotting. The interaction between miR-9-5p and DDX17 was identified by luciferase reporter assay. H&E staining was used to test morphological structure of femurs of rats with STZ treatment.

Results

MiR-9-5p was overexpressed in HG-treated BMSCs, while DDX17 was downregulated. Functionally, miR-9-5p knockdown promoted BMSCs osteogenic differentiation under HG condition. Mechanically, miR-9-5p targeted DDX17. DDX17 knockdown reversed the effect of miR-9-5p silencing on osteogenic differentiation of HG-treated BMSCs. In in vivo studies, miR-9-5p downregulation ameliorated the DOP condition of rats and miR-9-5p expression was negatively correlated with DDX17 expression in bone tissues of rats with STZ treatment.

Conclusion

MiR-9-5p knockdown promotes HG-induced osteogenic differentiation BMSCs in vitro and mitigates the DOP condition of rats in vivo by targeting DDX17.

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Funding

The work was supported by Lianyungang Second People's Hospital Qinglan Inheritance Project.

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  1. Chuanmei He and Mingming Liu have contributed equally to this work.

Authors and Affiliations

  1. Department of Nephrology, The Affiliated Lianyungang No.2 Hospital of Bengbu Medical College, Lianyungang, 222000, Jiangsu, China

    Chuanmei He

  2. Department of Orthopedics, The Affiliated Lianyungang No.2 Hospital of Bengbu Medical College, Lianyungang, 222000, Jiangsu, China

    Mingming Liu

  3. Department of Endocrinology, The Affiliated Lianyungang No.2 Hospital of Bengbu Medical College, 41 Hailian East Road, Haizhou District, Lianyungang, 222000, Jiangsu, China

    Qun Ding & Tongdao Xu

  4. Department of Laboratory, The Affiliated Lianyungang No.2 Hospital of Bengbu Medical College, Lianyungang, 222000, Jiangsu, China

    Fumeng Yang

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  1. Chuanmei He
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He, C., Liu, M., Ding, Q. et al. Upregulated miR-9-5p inhibits osteogenic differentiation of bone marrow mesenchymal stem cells under high glucose treatment. J Bone Miner Metab 40, 208–219 (2022). https://doi.org/10.1007/s00774-021-01280-9

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