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胫骨骨折后大鼠脊髓的时间转录组动力学揭示了脊髓与骨骼之间的串扰。

Temporal transcriptomic dynamics in rat spinal cord after tibial fracture unveil crosstalk between spinal cord and bone.

作者信息

Deng Jin, Wang Shen, Yuan Shaoxun, Lu Qingguo, Gu Xinyi, Huang Chen, Guo Shuhang, Yu Dehong, Yin Xiaofeng

机构信息

Department of Orthopedics and Traumatology, Peking University People's Hospital, Beijing, China.

Key Laboratory of Trauma and Neural Regeneration, Peking University, Beijing, China.

出版信息

Sci Rep. 2025 Sep 1;15(1):32147. doi: 10.1038/s41598-025-17561-6.

DOI:10.1038/s41598-025-17561-6
PMID:40890429
Abstract

Spinal cord injury induces progressive bone loss and increases fracture susceptibility. While the neurological consequences of skeletal trauma remain poorly characterized, underlying molecular mechanisms require systematic investigation. To systematically characterize the temporal dynamics of spinal cord responses, L4-L5 spinal segments were harvested from Sprague-Dawley rats at 0, 3, 7, 14, and 28 days post-fracture for RNA sequencing (Illumina platform). Integrated bioinformatics analyses revealed temporally stratified differentially expressed genes (DEGs). Quantitative real-time reverse transcription-polymerase chain reaction (qRT-PCR) was used to validate the expression of key genes. Transcriptomic changes peaked at 3 days and 7 days post-fracture. By day 14, transcriptomic signatures shifted toward synaptic plasticity-related pathways. DEGs were substantially reduced by day 28. Key genes (PCP4 and RICTOR) identified by bioinformatics were validated via qRT-PCR, confirming their temporal expression patterns. This study elucidates temporal dynamics of spinal cord transcriptomic remodeling post-fracture, establishing a foundation for understanding neuro-osseous cross-talk during bone healing.

摘要

脊髓损伤会导致进行性骨质流失并增加骨折易感性。虽然骨骼创伤的神经学后果仍未得到充分表征,但潜在的分子机制需要系统研究。为了系统地表征脊髓反应的时间动态,在骨折后0、3、7、14和28天从Sprague-Dawley大鼠中采集L4-L5脊髓节段用于RNA测序(Illumina平台)。综合生物信息学分析揭示了时间分层的差异表达基因(DEG)。定量实时逆转录聚合酶链反应(qRT-PCR)用于验证关键基因的表达。转录组变化在骨折后3天和7天达到峰值。到第14天,转录组特征转向与突触可塑性相关的途径。到第28天,DEG大幅减少。通过生物信息学鉴定的关键基因(PCP4和RICTOR)通过qRT-PCR得到验证,证实了它们的时间表达模式。本研究阐明了骨折后脊髓转录组重塑的时间动态,为理解骨愈合过程中的神经-骨相互作用奠定了基础。

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Genes (Basel). 2024 Nov 2;15(11):1431. doi: 10.3390/genes15111431.
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KEGG: biological systems database as a model of the real world.京都基因与基因组百科全书(KEGG):作为现实世界模型的生物系统数据库。
Nucleic Acids Res. 2025 Jan 6;53(D1):D672-D677. doi: 10.1093/nar/gkae909.
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Transcriptomic Analysis of the Rat Dorsal Root Ganglion After Fracture.骨折后大鼠背根神经节的转录组分析。
Mol Neurobiol. 2024 Mar;61(3):1467-1478. doi: 10.1007/s12035-023-03637-9. Epub 2023 Sep 19.
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Chem Commun (Camb). 2023 Apr 18;59(32):4726-4741. doi: 10.1039/d3cc00718a.
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Human striatal glia differentially contribute to AD- and PD-specific neurodegeneration.人类纹状体神经胶质细胞对 AD 和 PD 特异性神经退行性变有不同的贡献。
Nat Aging. 2023 Mar;3(3):346-365. doi: 10.1038/s43587-023-00363-8. Epub 2023 Feb 9.
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BIN1 is a key regulator of proinflammatory and neurodegeneration-related activation in microglia.BIN1 是小胶质细胞中促炎和神经退行性变相关激活的关键调节因子。
Mol Neurodegener. 2022 May 7;17(1):33. doi: 10.1186/s13024-022-00535-x.
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NGF-p75 signaling coordinates skeletal cell migration during bone repair.NGF-p75 信号在骨修复过程中协调骨骼细胞迁移。
Sci Adv. 2022 Mar 18;8(11):eabl5716. doi: 10.1126/sciadv.abl5716.
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