Comparative Single-Cell Analysis Reveals Tendon Progenitor Dysfunction by Age-Associated Oxidative Stress and Its Restoration by Antioxidant Treatments

IF 4.5 2区生物学 Q2 CELL BIOLOGY

Journal of Cellular Physiology Pub Date : 2025-02-23 DOI:10.1002/jcp.70016

Youngjae Jeong, Dongwook Yang, Jea Giezl Solidum, Laura Ortinau, Dongsu Park

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引用次数: 0

Abstract

Impaired healing of adult tendons with fibrosis remains clinical challenges while neonatal tendons have full functional restoration. However, age-associated cellular and molecular changes in tendon cells and tendon stem/progenitor cells (TSPCs) remain unknown. Here, comparative single cell transcriptomics of early postnatal (2 weeks old) and adult (20 weeks old) mouse tendons revealed that adult tendons have reduced number of TSPCs, decreased gene expression in tendon and cartilage development, and a greater population of fibro-tenogenic cells. Notably, adult TSPCs and tenocytes exhibit increased expression of immune-response and oxidative-stress genes with higher EGFR but decreased IGF signaling. Adult tendon cells show increased levels of intracellular reactive oxygen species (ROS) in vivo. In contrast, antioxidant treatment of adult tendons significantly reduces intracellular ROS of TSPCs and improves tendon strength in vivo. Hence, these findings suggest that increased inflammation and ROS during tendon aging deteriorates tendon function and regeneration that can be mitigated by antioxidant treatment.

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比较单细胞分析揭示年龄相关氧化应激引起的肌腱祖细胞功能障碍及其通过抗氧化处理恢复

成人肌腱纤维化损伤愈合仍然是临床挑战，而新生儿肌腱有完全的功能恢复。然而，肌腱细胞和肌腱干/祖细胞（TSPCs）中与年龄相关的细胞和分子变化仍然未知。本研究通过比较出生后早期（2周龄）和成年（20周龄）小鼠肌腱的单细胞转录组学发现，成年肌腱的TSPCs数量减少，肌腱和软骨发育中的基因表达减少，纤维肌腱生成细胞数量增加。值得注意的是，成年TSPCs和小细胞表现出免疫反应和氧化应激基因的表达增加，EGFR升高，但IGF信号传导降低。成人肌腱细胞在体内表现出细胞内活性氧（ROS）水平的增加。相反，成人肌腱抗氧化处理显著降低TSPCs细胞内ROS，提高体内肌腱强度。因此，这些研究结果表明，在肌腱老化过程中，炎症和ROS的增加会使肌腱功能和再生恶化，这可以通过抗氧化处理来缓解。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Journal of Cellular Physiology 生物-生理学

CiteScore

14.70

自引率

0.00%

发文量

256

审稿时长

1 months

期刊介绍： The Journal of Cellular Physiology publishes reports of high biological significance in areas of eukaryotic cell biology and physiology, focusing on those articles that adopt a molecular mechanistic approach to investigate cell structure and function. There is appreciation for the application of cellular, biochemical, molecular and in vivo genetic approaches, as well as the power of genomics, proteomics, bioinformatics and systems biology. In particular, the Journal encourages submission of high-interest papers investigating the genetic and epigenetic regulation of proliferation and phenotype as well as cell fate and lineage commitment by growth factors, cytokines and their cognate receptors and signal transduction pathways that influence the expression, integration and activities of these physiological mediators. Similarly, the Journal encourages submission of manuscripts exploring the regulation of growth and differentiation by cell adhesion molecules in addition to the interplay between these processes and those induced by growth factors and cytokines. Studies on the genes and processes that regulate cell cycle progression and phase transition in eukaryotic cells, and the mechanisms that determine whether cells enter quiescence, proliferate or undergo apoptosis are also welcomed. Submission of papers that address contributions of the extracellular matrix to cellular phenotypes and physiological control as well as regulatory mechanisms governing fertilization, embryogenesis, gametogenesis, cell fate, lineage commitment, differentiation, development and dynamic parameters of cell motility are encouraged. Finally, the investigation of stem cells and changes that differentiate cancer cells from normal cells including studies on the properties and functions of oncogenes and tumor suppressor genes will remain as one of the major interests of the Journal.