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Introduction <p>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.</p> Methods <p>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 <i>P53</i>, <i>P21</i>, lncRNA ROR, and lncRNA DINO were quantified using qRT-PCR.</p> Results <p>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 <i>P53</i> expression (1.3-fold) in the 30 mM group (<i>p</i> &lt; 0.0001) and 1.8-fold in the 40 mM group (<i>p</i> &lt; 0.0001). In addition, <i>P21</i> and lncRNA DINO were significantly upregulated, whereas lncRNA ROR expression was markedly downregulated.</p> Conclusion <p>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.</p>

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Expression of long non-coding RNAs DINO and ROR in bone marrow stem cells under hyperglycemic conditions

  • 期刊论文

  • 发表日期：

    2026年1月3日

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  • Sanaz Tavakoli,
  • Hamidreza Vaziri,
  • Mahshid Hodjat,
  • Shokoufeh Hassani

摘要

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.