IF 3.9 2区 医学 Q2 ENDOCRINOLOGY & METABOLISM
Frontiers in Endocrinology Pub Date : 2024-12-10 eCollection Date: 2024-01-01 DOI:10.3389/fendo.2024.1479909
Zezhong Liu, Yongqi Sun, Jiaoyi Pan, Kechun Guo, Zhi Tang, Xiaofeng Wang
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引用次数: 0

摘要

背景:软骨细胞和滑膜细胞参与了骨关节炎(OA)的发病机制。然而,OA滑膜细胞和软骨细胞之间的相互作用和相关性仍不清楚。本研究旨在阐明OA滑膜细胞和软骨细胞之间的相互作用和相关性,从而加深对OA发病机制的认识:方法:采用单细胞测序分析方法,对OA数据集中的滑膜细胞和软骨细胞集群进行分析。通过细胞相互作用分析,进一步探讨了这两种细胞类型之间潜在的相互作用。差异基因表达分析用于研究滑膜相关细胞群之间的差异:结果:该研究通过单细胞测序分析确定了滑膜成纤维细胞的具体特征。随后的细胞相互作用分析显示,滑膜成纤维细胞群与受损和未受损软骨中的细胞群之间存在相互作用和相关性。CILP+成纤维细胞与非受损软骨细胞之间存在显著的相互作用,而POSTN+成纤维细胞与受损软骨细胞之间存在显著的相互作用。此外,差异基因表达分析表明,PRELP、CLU、COMP、TNFRSF12A、INHBA、CILP 和 SERPINE2 等基因在 CILP+ 成纤维细胞中明显上调。这些基因参与促进细胞增殖、抑制炎症通路和稳定细胞结构,从而对软骨细胞发挥修复和保护作用。相反,COL6A3、COL6A1、COL1A2、COL1A1、COL3A1、TGF-β1、MMP2、AEBP1、SPARC、FNDC1 和 POSTN 在 POSTN+ 成纤维细胞中上调。这些基因可能会通过促进软骨细胞分解、驱动炎症、激活炎症通路以及促进软骨细胞凋亡和破坏,造成软骨细胞损伤和进一步退化:我们的研究阐明了OA滑膜细胞与软骨细胞之间的相互作用和相关性。CILP+滑膜成纤维细胞可通过促进细胞增殖、抑制炎症和稳定细胞结构,对OA患者的软骨细胞产生修复和保护作用,从而可能减轻患者软骨病变的进展。与此相反,POSTN+滑膜成纤维细胞可能会通过增强降解、炎症和细胞凋亡来加剧OA患者软骨细胞的退化,从而加重软骨病变。研究OA滑膜细胞和软骨细胞之间的潜在分子机制可加深对OA发病机制的认识,并为OA的临床诊断和治疗提供有价值的见解。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Single-cell profiling uncovers synovial fibroblast subpopulations associated with chondrocyte injury in osteoarthritis.

Background: Chondrocytes and synovial cells participate in the pathogenesis of osteoarthritis (OA). Nonetheless, the interactions and correlations between OA synovial cells and chondrocytes remain unclear. This study aims to elucidate the interactions and correlations between OA synovial cells and chondrocytes, so as to deepen understanding of OA pathogenesis.

Methods: Single-cell sequencing analysis was employed to analyze clusters of synovial and chondrocyte cells within the OA dataset. Through cell interaction analysis, the potential interactions between these two cell types were further explored. Differential gene expression analysis was used to examine the differences among synovial-related cell clusters.

Results: The study identified specific characteristics of synovial fibroblasts through single-cell sequencing analysis. Subsequent cell interaction analysis revealed interactions and correlations between synovial fibroblast clusters and cell clusters in both damaged and non-damaged cartilages. CILP+ fibroblasts showed significant interactions with non-damaged chondrocytes, while POSTN+ fibroblasts exhibited significant interactions with damaged chondrocytes. Furthermore, differential gene expression analysis revealed that genes such as PRELP, CLU, COMP, TNFRSF12A, INHBA, CILP, and SERPINE2, were significantly upregulated in CILP+ fibroblasts. These genes are involved in promoting cell proliferation, inhibiting inflammatory pathways, and stabilizing cell structure, thereby exerting reparative and protective effects on chondrocytes. In contrast, COL6A3, COL6A1, COL1A2, COL1A1, COL3A1, TGF-β1, MMP2, AEBP1, SPARC, FNDC1, and POSTN were upregulated in POSTN+ fibroblasts. These genes may contribute to chondrocyte damage and further degeneration by promoting chondrocyte catabolism, driving inflammation, activating inflammatory pathways, and facilitating chondrocyte apoptosis and destruction.

Conclusion: Our study elucidated the interactions and correlations between OA synovial cells and chondrocytes. CILP+ synovial fibroblasts may exert reparative and protective effects on chondrocytes of patients with OA by promoting cell proliferation, inhibiting inflammation, and stabilizing cellular structures, thereby potentially mitigating the progression of cartilage lesions in affected patients. In contrast, POSTN+ synovial fibroblasts may exacerbate chondrocyte deterioration in patients with OA by enhancing degradation, inflammation, and apoptosis, thereby exacerbating cartilage lesions. Investigating the underlying molecular mechanisms between OA synovial cells and chondrocytes refines the understanding of OA pathogenesis and provides valuable insights for the clinical diagnosis and treatment of OA.

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来源期刊
Frontiers in Endocrinology
Frontiers in Endocrinology Medicine-Endocrinology, Diabetes and Metabolism
CiteScore
5.70
自引率
9.60%
发文量
3023
审稿时长
14 weeks
期刊介绍: Frontiers in Endocrinology is a field journal of the "Frontiers in" journal series. In today’s world, endocrinology is becoming increasingly important as it underlies many of the challenges societies face - from obesity and diabetes to reproduction, population control and aging. Endocrinology covers a broad field from basic molecular and cellular communication through to clinical care and some of the most crucial public health issues. The journal, thus, welcomes outstanding contributions in any domain of endocrinology. Frontiers in Endocrinology publishes articles on the most outstanding discoveries across a wide research spectrum of Endocrinology. The mission of Frontiers in Endocrinology is to bring all relevant Endocrinology areas together on a single platform.
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