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

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. Graphical Abstract