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补骨脂素与负载外泌体的 SPC25 协同作用,减轻椎间盘退变中髓核细胞衰老。

Psoralen synergizes with exosome-loaded SPC25 to alleviate senescence of nucleus pulposus cells in intervertebral disc degeneration.

机构信息

Department of Spine, The First Affiliated Hospital of Hunan University of Traditional Chinese Medicine, No. 95 Shaoshan Middle Road, Yuhua District, Changsha, 410007, Hunan, People's Republic of China.

出版信息

J Orthop Surg Res. 2023 Oct 24;18(1):622. doi: 10.1186/s13018-023-04085-w.

Abstract

OBJECTIVE

To explore the mechanism of psoralen synergized with exosomes (exos)-loaded SPC25 on nucleus pulposus (NP) cell senescence in intervertebral disc degeneration (IVDD).

METHODS

IVDD cellular models were established on NP cells by tert-butyl hydroperoxide (TBHP) induction, followed by the treatment of psoralen or/and exos from adipose-derived stem cells (ADSCs) transfected with SPC25 overexpression vector (ADSCs-oe-SPC25-Exos). The viability, cell cycle, apoptosis, and senescence of NP cells were examined, accompanied by the expression measurement of aggrecan, COL2A1, Bcl-2, Bax, CDK2, p16, and p21.

RESULTS

After TBHP-induced NP cells were treated with psoralen or ADSCs-oe-SPC25-Exos, cell proliferation and the expression of aggrecan, COL2A1, Bcl-2, and CDK2 were promoted; however, the expression of Bax, p16, p21, and inflammatory factors was decreased, and cell senescence, cycle arrest, and apoptosis were inhibited. Of note, psoralen combined with ADSCs-oe-SPC25-Exos further decelerated NP cell senescence and cycle arrest compared to psoralen or ADSCs-oe-SPC25-Exos alone.

CONCLUSION

Combined treatment of psoralen and ADSCs-oe-SPC25-Exos exerted an alleviating effect on NP cell senescence, which may provide an insightful idea for IVDD treatment.

摘要

目的

探讨补骨脂素协同负载 SPC25 的外泌体(exos)对椎间盘退变(IVDD)中髓核细胞衰老的作用机制。

方法

通过叔丁基过氧化氢(TBHP)诱导建立椎间盘细胞模型,然后用补骨脂素或/和转染 SPC25 过表达载体的脂肪来源干细胞(ADSCs)来源的 exos 处理 NP 细胞。检测 NP 细胞的活力、细胞周期、凋亡和衰老情况,并测定聚集蛋白聚糖、COL2A1、Bcl-2、Bax、CDK2、p16 和 p21 的表达。

结果

TBHP 诱导的 NP 细胞用补骨脂素或 ADSCs-oe-SPC25-Exos 处理后,细胞增殖和聚集蛋白聚糖、COL2A1、Bcl-2 和 CDK2 的表达均得到促进;然而,Bax、p16、p21 和炎症因子的表达减少,细胞衰老、周期阻滞和凋亡受到抑制。值得注意的是,与单独使用补骨脂素或 ADSCs-oe-SPC25-Exos 相比,补骨脂素联合 ADSCs-oe-SPC25-Exos 进一步延缓了 NP 细胞衰老和周期阻滞。

结论

补骨脂素和 ADSCs-oe-SPC25-Exos 的联合治疗对 NP 细胞衰老具有缓解作用,为 IVDD 的治疗提供了新的思路。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9510/10594823/a5e02841647b/13018_2023_4085_Fig1_HTML.jpg

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