circRNA_0006393 promotes osteogenesis in glucocorticoid‑induced osteoporosis by sponging miR‑145‑5p and upregulating FOXO1

  • Authors:
    • Xing‑Bo Wang
    • Peng‑Biao Li
    • Shi‑Fang Guo
    • Qing‑Shan Yang
    • Zhi‑Xin Chen
    • Dachuan Wang
    • Song‑Bo Shi
  • View Affiliations

  • Published online on: July 12, 2019     https://doi.org/10.3892/mmr.2019.10497
  • Pages: 2851-2858
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Abstract

Glucocorticoids are the most common cause of glucocorticoid‑induced osteoporosis (GIOP). Moreover, the role of circular RNAs (circRNAs) in the regulation of bone metabolism remains unclear. Therefore, in the present study, it was hypothesized that hsa_circ_0006393 may play an important role in GIOP. To investigate the role of circRNAs in GIOP, treatment with dexamethasone or transfection with a vector overexpressing hsa_circ_0006393 were performed using in vitro cell and in vivo mouse models. Reverse transcription‑quantitative PCR, fluorescence in situ hybridization and western blotting were performed to investigate the function of hsa_circ_0006393 in vitro. In addition, the effects of hsa_circ_0006393 on osteogenesis were investigated. Dual‑energy X‑ray absorptiometry analysis was performed to examine the osteogenic potential of hsa_circ_0006393 in vivo. Moreover, the mechanism underlying hsa_circ_0006393‑mediated bone metabolism regulation via the microRNA (miR)‑145‑5p/forkhead box O1 (FOXO1) pathway was investigated. The present results suggested that the expression level of hsa_circ_0006393 was decreased in patients with GIOP. Furthermore, the overexpression of hsa_circ_0006393 increased the expression level of genes associated with osteogenesis. Moreover, hsa_circ_0006393 was identified to be localized mainly in the cytoplasm and nucleus of bone marrow mesenchymal stem cells. miR‑145‑5p was found to be directly targeted by hsa_circ_0006393. Collectively, hsa_circ_0006393 increases the expression levels of osteogenic genes during bone remodeling by sponging miR‑145‑5p and upregulating FOXO1.

References

1 

Weinstein RS: Glucocorticoid-induced osteoporosis and osteonecrosis. Endocrinol Metab Clin North Am. 41:595–611. 2012. View Article : Google Scholar : PubMed/NCBI

2 

Krasselt M and Baerwald C: An update on glucocorticoid-induced osteoporosis. Dtsch Med Wochenschr. 141:352–357. 2016.(In German). PubMed/NCBI

3 

Güler-Yüksel M, Hoes JN, Bultink IEM and Lems WF: Glucocorticoids, inflammation and bone. Calcif Tissue Int. 102:592–606. 2018. View Article : Google Scholar : PubMed/NCBI

4 

Jia D, O'Brien CA, Stewart SA, Manolagas SC and Weinstein RS: Glucocorticoids act directly on osteoclasts to increase their life span and reduce bone density. Endocrinology. 147:5592–5599. 2006. View Article : Google Scholar : PubMed/NCBI

5 

O'Brien CA, Jia D, Plotkin LI, Bellido T, Powers CC, Stewart SA, Manolagas SC and Weinstein RS: Glucocorticoids act directly on osteoblasts and osteocytes to induce their apoptosis and reduce bone formation and strength. Endocrinology. 145:1835–1841. 2004. View Article : Google Scholar : PubMed/NCBI

6 

Weinstein RS: Clinical practice. Glucocorticoid-induced bone disease. N Engl J Med. 365:62–70. 2011. View Article : Google Scholar : PubMed/NCBI

7 

Whittier X and Saag KG: Glucocorticoid-induced osteoporosis. Rheum Dis Clin North Am. 42:177–189. 2016. View Article : Google Scholar : PubMed/NCBI

8 

Zhang J, Liu H, Hou L, Wang G, Zhang R, Huang Y, Chen X and Zhu J: Circular RNA_LARP4 inhibits cell proliferation and invasion of gastric cancer by sponging miR-424-5p and regulating LATS1 expression. Mol Cancer. 16:1512017. View Article : Google Scholar : PubMed/NCBI

9 

Wang R, Zhang S, Chen X, Li N, Li J, Jia R, Pan Y and Liang H: circNT5E acts as a sponge of microRNA-422a to promote glioblastoma tumorigenesis. Cancer Res. 78:4812–4825. 2018. View Article : Google Scholar : PubMed/NCBI

10 

Li B and Li X: Overexpression of hsa_circ_0007534 predicts unfavorable prognosis for osteosarcoma and regulates cell growth and apoptosis by affecting AKT/GSK-3β signaling pathway. Biomed Pharmacother. 107:860–866. 2018. View Article : Google Scholar : PubMed/NCBI

11 

Song L and Xiao Y: Downregulation of hsa_circ_0007534 suppresses breast cancer cell proliferation and invasion by targeting miR-593/MUC19 signal pathway. Biochem Biophys Res Commun. 503:2603–2610. 2018. View Article : Google Scholar : PubMed/NCBI

12 

Kuang MJ, Xing F, Wang D, Sun L, Ma JX and Ma XL: circUSP45 inhibited osteogenesis in glucocorticoid-induced osteonecrosis of femoral head by sponging miR-127-5p through PTEN/AKT signal pathway: Experimental studies. Biochem Biophys Res Commun. 509:255–261. 2019. View Article : Google Scholar : PubMed/NCBI

13 

Shi C, Qi J, Huang P, Jiang M, Zhou Q, Zhou H, Kang H, Qian N, Yang Q, Guo L and Deng L: MicroRNA-17/20a inhibits glucocorticoid-induced osteoclast differentiation and function through targeting RANKL expression in osteoblast cells. Bone. 68:67–75. 2014. View Article : Google Scholar : PubMed/NCBI

14 

Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method. Methods. 25:402–408. 2001. View Article : Google Scholar : PubMed/NCBI

15 

Zhong S, Wang J, Zhang Q, Xu H and Feng J: CircPrimer: A software for annotating circRNAs and determining the specificity of circRNA primers. BMC Bioinformatics. 19:2922018. View Article : Google Scholar : PubMed/NCBI

16 

Tao SC, Yuan T, Rui BY, Zhu ZZ, Guo SC and Zhang CQ: Exosomes derived from human platelet-rich plasma prevent apoptosis induced by glucocorticoid-associated endoplasmic reticulum stress in rat osteonecrosis of the femoral head via the Akt/Bad/Bcl-2 signal pathway. Theranostics. 7:733–750. 2017. View Article : Google Scholar : PubMed/NCBI

17 

Liao L, Su X, Yang X, Hu C, Li B, Lv Y, Shuai Y, Jing H, Deng Z and Jin Y: TNF-α inhibits FoxO1 by upregulating miR-705 to aggravate oxidative damage in bone marrow-derived mesenchymal stem cells during osteoporosis. Stem cells. 34:1054–1067. 2016. View Article : Google Scholar : PubMed/NCBI

18 

Xu J, Gong H, Lu S, Deasey MJ and Cui Q: Animal models of steroid-induced osteonecrosis of the femoral head-a comprehensive research review up to 2018. Int Orthop. 42:1729–1737. 2018. View Article : Google Scholar : PubMed/NCBI

19 

Buckley L, Guyatt G, Fink HA, Cannon M, Grossman J, Hansen KE, Humphrey MB, Lane NE, Magrey M, Miller M, et al: 2017 American college of rheumatology guideline for the prevention and treatment of glucocorticoid-induced osteoporosis. Arthritis Rheumatol. 69:1521–1537. 2017. View Article : Google Scholar : PubMed/NCBI

20 

Xu D, Gao Y, Hu N, Wu L and Chen Q: miR-365 ameliorates dexamethasone-induced suppression of osteogenesis in MC3T3-E1 cells by targeting HDAC4. Int J Mol Sci. 18(pii): E9772017. View Article : Google Scholar : PubMed/NCBI

21 

Matsumoto A, Pasut A, Matsumoto M, Yamashita R, Fung J, Monteleone E, Saghatelian A, Nakayama KI, Clohessy JG and Pandolfi PP: mTORC1 and muscle regeneration are regulated by the LINC00961-encoded SPAR polypeptide. Nature. 541:228–232. 2017. View Article : Google Scholar : PubMed/NCBI

22 

Cheng X, Zhang L, Zhang K, Zhang G, Hu Y, Sun X, Zhao C, Li H, Li YM and Zhao J: Circular RNA VMA21 protects against intervertebral disc degeneration through targeting miR-200c and X linked inhibitor-of-apoptosis protein. Ann Rheum Dis. 77:770–779. 2018. View Article : Google Scholar : PubMed/NCBI

23 

Greco S, Cardinali B, Falcone G and Martelli F: Circular RNAs in muscle function and disease. Int J Mol Sc. 19(pii): E34542018. View Article : Google Scholar

24 

Song H, Xu D, Shi P, He B, Li Z, Ji Y, Agbeko CK and Wang J: Upregulated circ RNA hsa_circ_0000337 promotes cell proliferation, migration, and invasion of esophageal squamous cell carcinoma. Cancer Manag Res. 11:1997–2006. 2019. View Article : Google Scholar : PubMed/NCBI

25 

Xie F, Li Y, Wang M, Huang C, Tao D, Zheng F, Zhang H, Zeng F, Xiao X and Jiang G: Circular RNA BCRC-3 suppresses bladder cancer proliferation through miR-182-5p/p27 axis. Mol Cancer. 17:1442018. View Article : Google Scholar : PubMed/NCBI

26 

Wu Z, Huang W, Wang X, Wang T, Chen Y, Chen B, Liu R, Bai P and Xing J: Circular RNA CEP128 acts as a sponge of miR-145-5p in promoting the bladder cancer progression via regulating SOX11. Mol Med. 24:402018. View Article : Google Scholar : PubMed/NCBI

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September 2019
Volume 20 Issue 3

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Copy and paste a formatted citation
APA
Wang, X., Li, P., Guo, S., Yang, Q., Chen, Z., Wang, D., & Shi, S. (2019). circRNA_0006393 promotes osteogenesis in glucocorticoid‑induced osteoporosis by sponging miR‑145‑5p and upregulating FOXO1. Molecular Medicine Reports, 20, 2851-2858. https://doi.org/10.3892/mmr.2019.10497
MLA
Wang, X., Li, P., Guo, S., Yang, Q., Chen, Z., Wang, D., Shi, S."circRNA_0006393 promotes osteogenesis in glucocorticoid‑induced osteoporosis by sponging miR‑145‑5p and upregulating FOXO1". Molecular Medicine Reports 20.3 (2019): 2851-2858.
Chicago
Wang, X., Li, P., Guo, S., Yang, Q., Chen, Z., Wang, D., Shi, S."circRNA_0006393 promotes osteogenesis in glucocorticoid‑induced osteoporosis by sponging miR‑145‑5p and upregulating FOXO1". Molecular Medicine Reports 20, no. 3 (2019): 2851-2858. https://doi.org/10.3892/mmr.2019.10497