Ghrelin promotes the osteogenic differentiation of rMSCs via miR-206 and the ERK1/2 pathway
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ORIGINAL ARTICLE
Ghrelin promotes the osteogenic differentiation of rMSCs via miR-206 and the ERK1/2 pathway Nan Ye . Yifeng Yang . Zhongping Ma . Jian Huang
Received: 21 February 2020 / Accepted: 19 July 2020 Ó Springer Nature B.V. 2020
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
N. Ye Y. Yang Z. Ma J. Huang (&) Department of Cervical Surgery, The Second Affiliated Hospital of Inner Mongolia Medical University, Muslims Camp Square Road No 1, Hohhot, China e-mail: [email protected]
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. Keywords
Ghrelin miR-206 rMSCs ERK1/2
Introduction Ghrelin is a peptide composed of 28 amino acids; and as a gastric hormone, it can regulate many functions such as food intake and energy metabolism (Howick et al. 2020; Karim et al. 2020). Ghrelin was identified as the first endogenous ligand for the growth hormone secretagogue receptor (GHSR). Recently, it has been reported that ghrelin can inhibit apoptosis (Hao et al. 2016; Yu et al. 2015) and promote cell Survival (Li et al. 2014) of cardiomyocytes (Yang et al. 2011). In addition, many studies have reported that ghrelin can regulate the differentiation of mesoderm-derived precursor cells such as osteoblasts and preadipocytes (Xu et al. 2008; Liu et al. 2009; Ye and Jiang 2015). Micro(mi)RNAs, non-coding small RNAs, play a crucial role in the regulation of many genes (Zhang and Cohen 2013; Tay et al. 2014). MiRNAs target the 30 UTR of mRNAs with imperfect base-pairing, resulting in decreased translation or altered mRNA degradation (Beckman 2007). A recent study revealed that
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Cytotechnology
miR-206 is downregulated in osteoblast cells during osteogenesis, suggesting that miR
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