LncRNA ORLNC1 Promotes Bone Marrow Mesenchyml Stem Cell Pyroptosis Induced by Advanced Glycation End Production by Targeting miR-200b-3p/Foxo3 Pathway

Stem Cell Rev Rep. 2021 Dec;17(6):2262-2275. doi: 10.1007/s12015-021-10247-2. Epub 2021 Sep 4.

Abstract

Bone marrow mesenchymal stem cells (BMSCs) are a type of adult stem cells that originate from the mesoderm and have important roles in the body because of their self-renewal and multidirectional differentiation potential. Now it has been proved that BMSCs are closely related to the development of osteoporosis (OP). There is growing evidence that lncRNAs are involved in regulating the pyroptosis of BMSCs. And advanced glycation end-products (AGEs) have been recognized as NOD-like receptor family pyrin domain-containing protein 3 (NLRP3) inflammasome activators. In this study, we aimed to explore the role of lncRNA ORLNC1 (NONMMUT016106.2) on the pyroptosis of BMSCs under CML (Nε-(carboxymethyl) lysine, the most common AGEs) treatment and its specific molecular mechanisms. Our study revealed that CML treatment promoted pyroptosis of BMSCs and upregulated ORLNC1 expression. As a competing endogenous RNA (ceRNA) of miR-200b-3p, the level of ORLNC1 was negatively correlated with miR-200b-3p. Foxo3 was a target of miR-200b-3p and ORLNC1 promoted BMSCs pyroptosis induced by CML through targeting miR-200b-3p/Foxo3 pathway.

Keywords: BMSCs; Foxo3; Osteoporosis; Pyroptosis; lncRNA ORLNC1; miR-200b-3p.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bone Marrow / metabolism
  • Forkhead Box Protein O3 / genetics
  • Forkhead Box Protein O3 / metabolism
  • Humans
  • Mesenchymal Stem Cells* / metabolism
  • MicroRNAs* / genetics
  • Pyroptosis*
  • RNA, Long Noncoding* / genetics

Substances

  • FOXO3 protein, human
  • Forkhead Box Protein O3
  • MIRN200 microRNA, human
  • MicroRNAs
  • RNA, Long Noncoding