长链非编码 RNA 通过维持骨髓间充质干细胞活性促进骨再生。
Long noncoding RNA promotes bone regeneration by maintaining bone marrow mesenchymal stem cells activity.
机构信息
Department of Endocrinology, Endocrinology Research Center, Xiangya Hospital of Central South University, Changsha, Hunan, China.
National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Changsha, Hunan, China.
出版信息
PeerJ. 2022 Jun 9;10:e13475. doi: 10.7717/peerj.13475. eCollection 2022.
BACKGROUND
Long noncoding RNA can regulate hypothalamic neural stem cells (htNSCs) senescence and the aging process. However, the effect of on the senescence of bone marrow mesenchymal stem cells (BMSCs) and bone regeneration is unclear. In the present study, we investigated the effects of on the senescence of BMSCs and bone regeneration.
METHODS
knockout (-KO) and wild-type (WT) mice were used to establish a bone regeneration model. The Brdu labelling, CCK8 assay, wound healing assay, β-gal staining and osteogenic differentiation assay were used to assess the effects of on the functions of BMSCs. Micro-computed tomography (CT), histochemical and immunohistochemical staining were used to evaluate the ability of bone regeneration. The mimic of , theaflavin 3-gallate, was used to investigate its role on the senescence of BMSCs and bone regeneration.
RESULTS
The expression of reduced in BMSCs of middle-aged mice was compared with that of young mice. The deletion of was sufficient to drive the senescence of BMSCs, resulting in impaired bone regeneration in mice. Mechanistically, could interact with Y-box protein 1(YB-1) and delay its degradation, decreasing the transcription of of BMSCs. We also found that theaflavin 3-gallate could alleviate the senescence of BMSCs and promote bone regeneration in middle-aged mice.
CONCLUSION
These results indicated that played an important role on BMSCs senescence and bone regeneration and provided a therapeutic target to promote bone regeneration.
背景
长非编码 RNA 可调节下丘脑神经干细胞（htNSCs）衰老和衰老过程。然而，其对骨髓间充质干细胞（BMSCs）衰老和骨再生的影响尚不清楚。本研究旨在探讨对 BMSCs 衰老和骨再生的影响。
方法
使用敲除（-KO）和野生型（WT）小鼠建立骨再生模型。通过 Brdu 标记、CCK8 检测、划痕实验、β-gal 染色和成骨分化实验评估对 BMSCs 功能的影响。采用微计算机断层扫描（CT）、组织化学和免疫组织化学染色评估骨再生能力。使用 的模拟物，没食子儿茶素没食子酸酯（theaflavin 3-gallate），研究其对 BMSCs 衰老和骨再生的作用。
结果
与年轻小鼠相比，中年小鼠 BMSCs 中的表达减少。 的缺失足以驱动 BMSCs 衰老，导致小鼠骨再生受损。机制上， 可与 Y 盒蛋白 1（YB-1）相互作用并延缓其降解，降低 BMSCs 的转录。我们还发现没食子儿茶素没食子酸酯可减轻 BMSCs 衰老并促进中年小鼠骨再生。
结论
这些结果表明在 BMSCs 衰老和骨再生中发挥重要作用，并为促进骨再生提供了治疗靶点。
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