Scleraxis-expressing progenitor cells are critical for the maturation of the annulus fibrosus and demonstrate therapeutic potential

IF 5.9 1区医学 Q1 ORTHOPEDICS

Journal of Orthopaedic Translation Pub Date : 2025-05-01 DOI:10.1016/j.jot.2025.04.009

Hongtao Jia , Shuqin Chen , Xuye Hu , Jiajun Wang , Jinlong Suo , Sheng-Ming Dai , Weiguo Zou , Heng Feng

{"title":"Scleraxis-expressing progenitor cells are critical for the maturation of the annulus fibrosus and demonstrate therapeutic potential","authors":"Hongtao Jia , Shuqin Chen , Xuye Hu , Jiajun Wang , Jinlong Suo , Sheng-Ming Dai , Weiguo Zou , Heng Feng","doi":"10.1016/j.jot.2025.04.009","DOIUrl":null,"url":null,"abstract":"<div><h3>Background</h3><div>Annulus fibrosus (AF) is an important part of the intervertebral disc (IVD) and its injury leads to back pain and impaired mobility. The stem/progenitor cells are essential for the maturation and repair of the AF, however, the identity of AF stem/progenitor cells remain elusive.</div></div><div><h3>Methods</h3><div>In this study, we sorted cells from the murine IVDs and performed the single-cell RNA sequencing. Using single-cell transcriptomics, genetic lineage tracing, <em>in vitro</em> stem cell experiment, ablation models and cell transplantation, we elucidate the role of AF progenitor cells in maturation and injury.</div></div><div><h3>Results</h3><div>On the basis of single-cell RNA-sequencing (scRNA-seq) analysis of the intervertebral disc, we found that the transcription factor <em>Scleraxis</em> (<em>Scx</em>) can specifically label a progenitor cell population of the outer AF. By lineage tracing assay, <em>Scx</em>-lineage AF cells proliferate mainly prior to sexual maturity, but barely proliferate after age of 8 weeks. The <em>Scx</em>-expressing AF cells are enriched for stem/progenitor cell markers and show a higher proliferative capacity and differentiation potential than the <em>Scx</em><sup>−</sup> cells. The ablation of <em>Scx</em>-expressing AF cells impairs the maturation of AF. The <em>Scx</em><sup>+</sup> AF cells are enriched for TGFβ signaling. Transplantation of <em>Scx</em>-lineage cells to injured AF with Connective tissue growth factor (CTGF) improved the AF healing.</div></div><div><h3>Conclusions</h3><div><em>Scleraxis</em>-expressing progenitor cells are critical for the maturation of AF and demonstrate therapeutic potential for AF regeneration.</div></div><div><h3>The translational potential of this article</h3><div>These findings expand the important role of stem cells in maturation and repair and provide new strategy for cellular therapy of AF repair.</div></div>","PeriodicalId":16636,"journal":{"name":"Journal of Orthopaedic Translation","volume":"52 ","pages":"Pages 301-312"},"PeriodicalIF":5.9000,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Orthopaedic Translation","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S2214031X25000683","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"ORTHOPEDICS","Score":null,"Total":0}

引用次数: 0

Abstract

Background

Annulus fibrosus (AF) is an important part of the intervertebral disc (IVD) and its injury leads to back pain and impaired mobility. The stem/progenitor cells are essential for the maturation and repair of the AF, however, the identity of AF stem/progenitor cells remain elusive.

Methods

In this study, we sorted cells from the murine IVDs and performed the single-cell RNA sequencing. Using single-cell transcriptomics, genetic lineage tracing, in vitro stem cell experiment, ablation models and cell transplantation, we elucidate the role of AF progenitor cells in maturation and injury.

Results

On the basis of single-cell RNA-sequencing (scRNA-seq) analysis of the intervertebral disc, we found that the transcription factor Scleraxis (Scx) can specifically label a progenitor cell population of the outer AF. By lineage tracing assay, Scx-lineage AF cells proliferate mainly prior to sexual maturity, but barely proliferate after age of 8 weeks. The Scx-expressing AF cells are enriched for stem/progenitor cell markers and show a higher proliferative capacity and differentiation potential than the Scx⁻ cells. The ablation of Scx-expressing AF cells impairs the maturation of AF. The Scx⁺ AF cells are enriched for TGFβ signaling. Transplantation of Scx-lineage cells to injured AF with Connective tissue growth factor (CTGF) improved the AF healing.

Conclusions

Scleraxis-expressing progenitor cells are critical for the maturation of AF and demonstrate therapeutic potential for AF regeneration.

The translational potential of this article

These findings expand the important role of stem cells in maturation and repair and provide new strategy for cellular therapy of AF repair.

Abstract Image

查看原文本刊更多论文

表达硬化的祖细胞对纤维环的成熟至关重要，并显示出治疗潜力

纤维环（AF）是椎间盘（IVD）的重要组成部分，其损伤可导致背部疼痛和活动能力受损。干细胞/祖细胞在房颤的成熟和修复中起着至关重要的作用，然而，房颤干细胞/祖细胞的身份仍然是一个谜。方法本研究对小鼠ivd细胞进行分选，并进行单细胞RNA测序。通过单细胞转录组学、遗传谱系追踪、体外干细胞实验、消融模型和细胞移植，我们阐明了房颤祖细胞在成熟和损伤中的作用。结果通过对椎间盘单细胞rna测序（scRNA-seq）分析，我们发现转录因子scraxis （Scx）可以特异性标记外房颤的祖细胞群。通过谱系追踪实验，scraxis谱系房颤细胞主要在性成熟之前增殖，但在8周后几乎没有增殖。表达Scx的AF细胞具有丰富的干细胞/祖细胞标记，并表现出比Scx−细胞更高的增殖能力和分化潜力。表达Scx的AF细胞的消融会损害AF的成熟。Scx+ AF细胞富含tgf - β信号。结缔组织生长因子（CTGF）联合scx系细胞移植损伤心房，可促进心房愈合。结论表达sscleraxis的祖细胞在房颤成熟过程中起着至关重要的作用，并具有治疗房颤再生的潜力。这些发现拓展了干细胞在成熟和修复中的重要作用，并为心房颤动修复的细胞治疗提供了新的策略。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Journal of Orthopaedic Translation Medicine-Orthopedics and Sports Medicine

CiteScore

11.80

自引率

13.60%

发文量

审稿时长

29 days

期刊介绍： The Journal of Orthopaedic Translation (JOT) is the official peer-reviewed, open access journal of the Chinese Speaking Orthopaedic Society (CSOS) and the International Chinese Musculoskeletal Research Society (ICMRS). It is published quarterly, in January, April, July and October, by Elsevier.