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miR-363-3p is activated by MYB and regulates osteoporosis pathogenesis via PTEN/PI3K/AKT signaling pathway

  • Mingyi Li
  • Ruolan LuoEmail author
  • Wenjian Yang
  • Zhen Zhou
  • Chenxia Li
Article
  • 101 Downloads

Abstract

Osteoporosis results from the imbalance between osteogenesis and bone resorption mediated by osteoblasts and osteoclasts. During the disease process of osteoporosis, the alteration of gene expression occurs, which lead to the disease progression. MicroRNAs (miRNAs) have been previously demonstrated to be modulators for bone metabolism via regulation of osteoblast and osteoclast differentiation. In the present study, we detected the expression levels of five osteoporosis-related miRNAs in bone and serum samples of patient with or without osteoporosis. The downstream molecular mechanism of miR-363-3p was analyzed and detected by using bioinformatics analysis and mechanism experiment. The upstream transcription factor of miR-363-3p was analyzed by applying bioinformatics analysis and ChIP assay and luciferase reporter assay. The role of this pathway in osteoclastogenesis was demonstrated by functional assays. MiR-363-3p was significantly highly expressed in osteoporotic samples. Mechanistically, miR-363-3p promotes osteoclastogenesis and inhibits osteogenic differentiation by targeting PTEN and therefore activating PI3K/AKT signaling pathway. MiR-363-3p was activated by its upstream transcription activator MYB. This study revealed that MYB-induced upregulation of miR-363-3p regulates osteoporosis pathogenesis via PTEN/PI3K/AKT signaling pathway.

Keywords

MYB miR-363-3p Osteoporosis PTEN PI3K/AKT signaling pathway 

Notes

Acknowledgments

The authors thank all members contributed to this study.

Compliance with ethical standards

This study was approved by the Research Ethics Committee of Xiangyang No.1 People’s Hospital.

Conflict of interest

The authors declare that they have no conflict of interest.

Supplementary material

11626_2019_344_Fig7_ESM.png (125 kb)
Supplementary figure 1

The expression of several miRNAs in the bone and serum samples. A-B. The level of indicated miRNAs (miR-214, miR-34a, miR-103a, miR-503 and miR-148a), whose function in osteoporosis has already been reported previously, was detected using qRT-PCR analysis in 6 pairs of bone tissues (A) and 6 pairs of serum samples (B). *P < 0.05, **P < 0.01. (PNG 124 kb)

11626_2019_344_MOESM1_ESM.tif (4.8 mb)
High Resolution Image (TIF 4913 kb)
11626_2019_344_Fig8_ESM.png (459 kb)
Supplementary figure 2

The expression of genes involved in miR-363-3p/PTEN/PI3K/AKT axis during osteoclast differentiation. A-B. qRT-PCR analysis indicated that miR-363-3p level was increased while PTEN expression decreased in a time-dependent manner in CD14 + PBMCs under M-CSF and RANKL treatment. C. The protein levels of PTEN, AKT and p-AKT in CD14 + PBMCs when co-treating with M-CSF and RANKL for 0, 24, 48, and 72 h were evaluated by Western blot analysis. *P < 0.05, **P < 0.01. (PNG 459 kb)

11626_2019_344_MOESM2_ESM.tif (8.9 mb)
High Resolution Image (TIF 9127 kb)
11626_2019_344_MOESM3_ESM.doc (36 kb)
Supplementary table 1 The expression of genes in the bone tissues from osteoporotic and non-osteoporotic patients. Low/high by the sample median. Paired-sample t test. P < 0.05 was thought to be of statistical significance. (DOC 35 kb)
11626_2019_344_MOESM4_ESM.docx (15 kb)
Supplementary table 2 The expression of genes in the serum samples from osteoporotic and non-osteoporotic patients. Low/high by the sample median. Paired-sample t test. P < 0.05 was thought to be of statistical significance. (DOCX 14 kb)

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Copyright information

© The Society for In Vitro Biology 2019

Authors and Affiliations

  1. 1.Endocrine Department, Xiangyang No.1 People’s HospitalHubei University of MedicineXiangyangChina
  2. 2.Endocrine DepartmentXiangyang Hospital of Traditional Chinese MedicineXiangyangChina

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