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miR-140-3p aggregates osteoporosis by targeting PTEN and activating PTEN/PI3K/AKT signaling pathway

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Abstract

Osteoporosis (OP) is a systemic bone metabolic disorder, which negatively affects the quality of life in the elders and postmenopausal females. Healthy volunteers and postmenopausal females with OP were enrolled in the present study. Bone densitometry (BMD) was detected by dual-energy X-ray absorptiometry (DXA). CD14+PBMCs and C2C12 cells were cultured to induce osteoclast differentiation and osteoblast differentiation, respectively. The interaction between miR‑140-3p and PTEN was predicted and verified by TargetScan 7.2 and dual luciferase reporter assay, respectively. miRNA/RNA level and protein level were detected by quantitative real-time polymerase chain reaction (qRT-PCR) and western blot, respectively. Cell proliferation and apoptosis were detected by 5-ethynyl-2′-deoxyuridine (EdU) staining and flow cytometry, respectively. Cell differentiation of CD14+PBMCs and C2C12 cells were detected by tartrate-resistant acid phosphatase (TRAP) staining and alizarin red staining, respectively. The activity of alkaline phosphatase (ALP) was detected by ALP assay. Differences were observed in age, body mass index (BMI), and BMD between the OP group and the control group. Higher miR‑140-3p level and lower PTEN level were found in PBMCs of OP group compared to control group; there was a negative correlation between them in the serum of OP group. miR-140-3p targeted and downregulated the expression of PTEN. miR-140-3p inhibitor inhibited cell proliferation, differentiation, and promoted cell apoptosis of CD14+PBMCs; while promoted cell proliferation, differentiation and inhibited cell apoptosis of C2C12 cells, by targeting PTEN and inactivating PTEN/PI3K/AKT signaling pathway. These findings suggested a potential therapeutic role of miR-140-3p in the treatment of patients with OP.

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Authors and Affiliations

  1. Department of Orthopedics, China-Japan Union Hospital, No. 126, Xiantai Street, Changchun, 130031, Jilin, China

    Ruofeng Yin, Jiajia Jiang, Rui Gu & Fei Wang

  2. Jilin Medical Products Administration, Changchun, 130033, Jilin, China

    Huimin Deng

  3. Department of Orthopaedics, Liaohe Hospital, Liaoyuan, 136299, Jilin, China

    Zhaobin Wang

Authors
  1. Ruofeng Yin
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  2. Jiajia Jiang
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  3. Huimin Deng
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  4. Zhaobin Wang
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  5. Rui Gu
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  6. Fei Wang
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Contributions

RY, JJ, and HD carried out the cell experiments; ZW collected the clinical samples and performed the clinical studies RY, RG, and FW analyzed the data; FW supervised and wrote the manuscript.

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Correspondence to Fei Wang.

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The authors declare that they have no conflict of interest.

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All procedures performed in the present study involving human participants were approved by the Ethic Committee of Liaohe Hospital (No. 20171221).

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Written informed consent for the publication of any associated data and accompanying images were provided by all patients prior to surgery.

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Yin, R., Jiang, J., Deng, H. et al. miR-140-3p aggregates osteoporosis by targeting PTEN and activating PTEN/PI3K/AKT signaling pathway. Human Cell 33, 569–581 (2020). https://doi.org/10.1007/s13577-020-00352-8

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  • DOI: https://doi.org/10.1007/s13577-020-00352-8

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