Skip to main content
Log in

Ghrelin promotes the osteogenic differentiation of rMSCs via miR-206 and the ERK1/2 pathway

  • Original Article
  • Published:
Cytotechnology Aims and scope Submit manuscript

Abstract

Objective

Mesenchymal stem cells (MSCs) can differentiate into chondroblasts, adipocytes, or osteoblasts under appropriate stimulation. Ghrelin, an endogenous ligand for the growth hormone secretagogue receptor (GHSR), stimulates growth hormone (GH) secretion and exerts both orexigenic and adipogenic effects. The ERK1/2 signaling pathway is known to trigger osteogenic differentiation of rabbit bone marrow-derived mesenchymal stromal cells. In the present study, the function of miR-206 in the ghrelin-mediated osteogenic differentiation of rabbit bone marrow-derived mesenchymal stromal cells (rMSCs) was explored.

Methods

The expression of miR-206 was detected by qPCR, and phosphorylated ERK1/2 and the protein expression levels of ALP, RUNX2, and Osterix were assessed by western blotting. Results: Ghrelin inhibited the expression of miR-206 to promote the osteogenic differentiation of rMSCs. Moreover, ghrelin increased the phosphorylation of ERK1/2, while overexpression of miR-206 suppressed ERK1/2 phosphorylation, indicating that miR-206 can regulate the ERK1/2 pathway. Further, inhibition of ERK1/2 had no influence on miR-206 expression; however, the phosphorylation of ERK1/2 was decreased, and the protein expression levels of ALP, RUNX2, and Osterix were downregulated. Conclusions: Ghrelin promotes the osteogenic differentiation of rMSCs via miR-206 and the ERK1/2 pathway.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  • Beckman M (2007) MicroRNAs found cavorting with p53. J Natl Cancer Inst 99:1664–1665

    Article  Google Scholar 

  • Chen Y et al (2019) miR-206 inhibits osteogenic differentiation of bone marrow mesenchymal stem cells by targetting glutaminase. Biosci Rep 39:3

    Google Scholar 

  • Flamant S et al (2019) Global MicroRNA profiling uncovers miR-206 as a negative regulator of hematopoietic commitment in human pluripotent stem cells. Int J Mol Sci 20:7

    Article  Google Scholar 

  • Fujitsuka N et al (2012) Efficacy of ghrelin in cancer cachexia: clinical trials and a novel treatment by rikkunshito. Crit Rev Oncog 17:277–284

    Article  Google Scholar 

  • Hao Y et al (2016) Ghrelin protects against depleted uranium-induced apoptosis of MC3T3-E1 cells through oxidative stress-mediated p38-mitogen-activated protein kinase pathway. Toxicol Appl Pharmacol 290:116–125

    Article  CAS  Google Scholar 

  • Hao XZ, Fan HM (2017) Identification of miRNAs as atherosclerosis biomarkers and functional role of miR-126 in atherosclerosis progression through MAPK signalling pathway. Eur Rev Med Pharmacol Sci 21:2725–2733

    PubMed  Google Scholar 

  • Howick K et al (2020) Behavioural characterization of ghrelin ligands, anamorelin and HM01: appetite and reward-motivated effects in rodents. Neuropharmacology 108:11

    Google Scholar 

  • Karim R et al (2020) Association of hot flushes with ghrelin and adipokines in early versus late postmenopausal women. Menopause 27:512–518

    Article  Google Scholar 

  • Li E et al (2014) Ghrelin stimulates proliferation, migration and differentiation of neural progenitors from the subventricular zone in the adult mice. Exp Neurol 252:75–84

    Article  CAS  Google Scholar 

  • Liu J et al (2009) [Effects of ghrelin on the proliferation and differentiation of 3T3-L1 preadipocytes and its possible mechanisms]. Zhongguo Dang Dai Er Ke Za Zhi 11:69–73

    PubMed  Google Scholar 

  • Liu F et al (2019) Over-expression of miR-206 decreases the Euthyrox-resistance by targeting MAP4K3 in papillary thyroid carcinoma. Biomed Pharmacother 114:108605

    Article  CAS  Google Scholar 

  • Mansoori B et al (2016) HMGI-C suppressing induces P53/caspase9 axis to regulate apoptosis in breast adenocarcinoma cells. Cell Cycle 15:2585–2592

    Article  CAS  Google Scholar 

  • Pedini F et al (2019) Joint action of miR-126 and MAPK/PI3K inhibitors against metastatic melanoma. Mol Oncol 13:1836–54

    Article  CAS  Google Scholar 

  • Tay Y et al (2014) Characterization of dual PTEN and p53-targeting microRNAs identifies microRNA-638/Dnm2 as a two-hit oncogenic locus. Cell Rep 8:714–722

    Article  CAS  Google Scholar 

  • Xu G et al (2008) Ghrelin and cell differentiation. Acta Biochim Biophys Sin (Shanghai) 40:841–847

    Article  CAS  Google Scholar 

  • Yang J et al (2011) Ghrelin promotes differentiation of human embryonic stem cells into cardiomyocytes. Acta Pharmacol Sin 32:1239–1245

    Article  CAS  Google Scholar 

  • Yang TR et al (2019) Resina draconis inhibits the endoplasmic-reticulum-induced apoptosis of myocardial cells via regulating miR-423-3p/ERK signaling pathway in a tree shrew myocardial ischemia-reperfusion model. J Biosci 44:2

    Article  Google Scholar 

  • Ye N, Jiang D (2015) Ghrelin accelerates the growth and osteogenic differentiation of rabbit mesenchymal stem cells through the ERK1/2 pathway. BMC Biotechnol 15:51

    Article  Google Scholar 

  • Ye N et al (2018) Ghrelin accelerates the cartilagic differentiation of rabbit mesenchymal stem cells through the ERK1/2 pathway. Cytotechnology 70:415–421

    Article  CAS  Google Scholar 

  • Yu J (2015) Ghrelin protects MES235 cells against rotenone via inhibiting mitochondrial dysfunction and apoptosis. Neuropeptides 56:69–74

    Article  Google Scholar 

  • Zhai W et al (2018) MiR-532-5p suppresses renal cancer cell proliferation by disrupting the ETS1-mediated positive feedback loop with the KRAS-NAP1L1/P-ERK axis. Br J Cancer 119:591–604

    Article  CAS  Google Scholar 

  • Zhang W, Cohen SM (2013) The Hippo pathway acts via p53 and microRNAs to control proliferation and proapoptotic gene expression during tissue growth. Biol Open 2:822–828

    Article  Google Scholar 

  • Zhang Z et al (2014) Bone marrow stromal cell-derived extracellular matrix promotes osteogenesis of adipose-derived stem cells. Cell Biol Int 39:291–9

    Article  CAS  Google Scholar 

  • Zhou J et al (2019) miR-206 regulates alveolar type II epithelial cell Cx43 expression in sepsis-induced acute lung injury. Exp Ther Med 18:296–304

    CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

This work was supported by the Inner Mongolia Natural Science Foundation (No. 2017BS0813).

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Jian Huang.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Ye, N., Yang, Y., Ma, Z. et al. Ghrelin promotes the osteogenic differentiation of rMSCs via miR-206 and the ERK1/2 pathway. Cytotechnology 72, 707–713 (2020). https://doi.org/10.1007/s10616-020-00413-8

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10616-020-00413-8

Keywords

Navigation