Zhang Lili, Li Shilun, Li Juan, Li Yukun
Department of Endocrinology, The Third Hospital of Hebei Medical University, Shijiazhuang, 050051, Hebei Province, People's Republic of China.
Department of Endocrinology, The Second Hospital of Shijiazhuang, Shijiazhuang, 050051, Hebei Province, People's Republic of China.
Stem Cell Rev Rep. 2021 Dec;17(6):2262-2275. doi: 10.1007/s12015-021-10247-2. Epub 2021 Sep 4.
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.
骨髓间充质干细胞(BMSCs)是一类起源于中胚层的成体干细胞,因其自我更新和多向分化潜能而在体内发挥重要作用。现已证明BMSCs与骨质疏松症(OP)的发生发展密切相关。越来越多的证据表明lncRNAs参与调节BMSCs的焦亡。晚期糖基化终产物(AGEs)已被认为是含NOD样受体家族pyrin结构域蛋白3(NLRP3)炎性小体激活剂。在本研究中,我们旨在探讨lncRNA ORLNC1(NONMMUT016106.2)在CML(Nε-(羧甲基)赖氨酸,最常见的AGEs)处理下对BMSCs焦亡的作用及其具体分子机制。我们的研究表明,CML处理促进了BMSCs的焦亡并上调了ORLNC1的表达。作为miR-200b-3p的竞争性内源性RNA(ceRNA),ORLNC1的水平与miR-200b-3p呈负相关。Foxo3是miR-200b-3p的靶标,ORLNC1通过靶向miR-200b-3p/Foxo3途径促进CML诱导的BMSCs焦亡。