Expression of Long Non-Coding Rnas Dino and Ror in Bone Marrow Stem Cells Under Hyperglycemic Conditions Publisher



Tavakoli S ; Vaziri H ; Hodjat M ; Hassani S
Source: Journal of Diabetes and Metabolic Disorders Published:2026

Abstract

Introduction: Diabetes is a prevalent metabolic disorder that affects multiple organ systems and leads to long-term complications. Mesenchymal stem cells (MSCs) play a crucial role in tissue homeostasis; however, their function is impaired under hyperglycemic conditions, which may limit their regenerative capacity. Long non-coding RNAs (lncRNAs) are key regulators of cellular signaling pathways involved in oxidative stress and DNA damage. This study investigates hyperglycemia-induced oxidative damage in MSCs, with a focus on the roles of lncRNA ROR and lncRNA DINO. Methods: Bone marrow-derived MSCs were exposed to 30 mM or 40 mM glucose for 3 or 9 days. Intracellular oxidative stress was evaluated using a fluorometric assay for ROS. DNA damage was assessed by comet assay. The expression levels of P53, P21, lncRNA ROR, and lncRNA DINO were quantified using qRT-PCR. Results: Exposure to hyperglycemic conditions (30 mM and 40 mM glucose) resulted in a significant increase in ROS levels, reaching up to 2.1-fold at both 3 and 9 days. Prolonged glucose exposure was associated with increased DNA damage, particularly in the 40 mM glucose group, as evidenced by a higher comet Olive tail moment compared with the 5 mM control (~ 51 versus ~ 20). Gene expression analysis demonstrated significant increase in P53 expression (1.3-fold) in the 30 mM group (p < 0.0001) and 1.8-fold in the 40 mM group (p < 0.0001). In addition, P21 and lncRNA DINO were significantly upregulated, whereas lncRNA ROR expression was markedly downregulated. Conclusion: Prolonged exposure to hyperglycemic condition induces oxidative stress–mediated DNA damage, likely through activation of the P53/P21 signaling axis. The regulation of lncRNA ROR and lncRNA DINO highlights their potential roles in modulating MSC responses to glucose-induced oxidative stress. These findings provide mechanistic insight into diabetes-associated MSC dysfunction and support the need for strategies that mitigate hyperglycemia-induced damage to preserve MSC regenerative potential in diabetic conditions. © The Author(s), under exclusive licence to Tehran University of Medical Sciences 2026.