Single-cell RNA sequencing analysis of human chondrocytes reveals cell–cell communication alterations mediated by interactive signaling pathways in osteoarthritis
Objective: Osteoarthritis (OA) is a common joint disorder characterized by degenerative articular cartilage, subchondral bone remodeling, and inflammation. Increasing evidence suggests that the substantial crosstalk between cartilage and synovium is closely related to Osteoarthritis development, but...
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| Format: | Article |
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Frontiers Media S.A.
2023-04-01
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| Series: | Frontiers in Cell and Developmental Biology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fcell.2023.1099287/full |
| _version_ | 1797853016708087808 |
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| author | Xin Kang Kailiang Zhang Yakang Wang Yang Zhao Yao Lu |
| author_facet | Xin Kang Kailiang Zhang Yakang Wang Yang Zhao Yao Lu |
| author_sort | Xin Kang |
| collection | DOAJ |
| description | Objective: Osteoarthritis (OA) is a common joint disorder characterized by degenerative articular cartilage, subchondral bone remodeling, and inflammation. Increasing evidence suggests that the substantial crosstalk between cartilage and synovium is closely related to Osteoarthritis development, but the events that cause this degeneration remain unknown. This study aimed to explore the alterations in intercellular communication involved in the pathogenesis of Osteoarthritis using bioinformatics analysis.Methods: Single-cell transcriptome sequencing (scRNA-seq) profiles derived from articular cartilage tissue of patients with Osteoarthritis were downloaded from a public database. Chondrocyte heterogeneity was assessed using computational analysis, and cell type identification and clustering analysis were performed using the “FindClusters” function in the Seurat package. Intercellular communication networks, including major signaling inputs and outputs for cells, were predicted, and analyzed using CellChat.Results: Seven molecularly defined chondrocytes clusters (homeostatic chondrocytes, hypertrophic chondrocyte (HTC), pre-HTC, regulatory chondrocytes, fibro-chondrocytes (FC), pre-FC, and reparative chondrocyte) with different compositions were identified in the damaged cartilage. Compared to those in the intact cartilage, the overall cell–cell communication frequency and communication strength were remarkably increased in the damaged cartilage. The cellular communication among chondrocyte subtypes mediated by signaling pathways, such as PTN, VISFATIN, SPP1, and TGF-β, was selectively altered in Osteoarthritis. Moreover, we verified that SPP1 pathway enrichment scores increased, but VISFATIN pathway enrichment scores decreased based on the bulk rna-seq datasets in Osteoarthritis.Conclusion: Our results revealed alterations in cell–cell communication among OA-related chondrocyte subtypes that were mediated by specific signaling pathways, which might be a crucial underlying mechanism associated with Osteoarthritis progression. |
| first_indexed | 2024-04-09T19:42:33Z |
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| id | doaj.art-d929f63eb406451e8eeeb34496f46fe1 |
| institution | Directory Open Access Journal |
| issn | 2296-634X |
| language | English |
| last_indexed | 2024-04-09T19:42:33Z |
| publishDate | 2023-04-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cell and Developmental Biology |
| spelling | doaj.art-d929f63eb406451e8eeeb34496f46fe12023-04-04T04:26:04ZengFrontiers Media S.A.Frontiers in Cell and Developmental Biology2296-634X2023-04-011110.3389/fcell.2023.10992871099287Single-cell RNA sequencing analysis of human chondrocytes reveals cell–cell communication alterations mediated by interactive signaling pathways in osteoarthritisXin Kang0Kailiang Zhang1Yakang Wang2Yang Zhao3Yao Lu4Department of Orthopaedic Surgery, Honghui Hospital, Xi’an Jiaotong University, Xi'an, Shaanxi, ChinaDepartment of Orthopedics, The 960th Hospital of the PLA Joint Logistics Support Force, Jinan, Shandong, ChinaDepartment of Orthopaedic Surgery, Honghui Hospital, Xi’an Jiaotong University, Xi'an, Shaanxi, ChinaDepartment of Orthopaedic Surgery, Honghui Hospital, Xi’an Jiaotong University, Xi'an, Shaanxi, ChinaDepartment of Orthopaedic Surgery, Honghui Hospital, Xi’an Jiaotong University, Xi'an, Shaanxi, ChinaObjective: Osteoarthritis (OA) is a common joint disorder characterized by degenerative articular cartilage, subchondral bone remodeling, and inflammation. Increasing evidence suggests that the substantial crosstalk between cartilage and synovium is closely related to Osteoarthritis development, but the events that cause this degeneration remain unknown. This study aimed to explore the alterations in intercellular communication involved in the pathogenesis of Osteoarthritis using bioinformatics analysis.Methods: Single-cell transcriptome sequencing (scRNA-seq) profiles derived from articular cartilage tissue of patients with Osteoarthritis were downloaded from a public database. Chondrocyte heterogeneity was assessed using computational analysis, and cell type identification and clustering analysis were performed using the “FindClusters” function in the Seurat package. Intercellular communication networks, including major signaling inputs and outputs for cells, were predicted, and analyzed using CellChat.Results: Seven molecularly defined chondrocytes clusters (homeostatic chondrocytes, hypertrophic chondrocyte (HTC), pre-HTC, regulatory chondrocytes, fibro-chondrocytes (FC), pre-FC, and reparative chondrocyte) with different compositions were identified in the damaged cartilage. Compared to those in the intact cartilage, the overall cell–cell communication frequency and communication strength were remarkably increased in the damaged cartilage. The cellular communication among chondrocyte subtypes mediated by signaling pathways, such as PTN, VISFATIN, SPP1, and TGF-β, was selectively altered in Osteoarthritis. Moreover, we verified that SPP1 pathway enrichment scores increased, but VISFATIN pathway enrichment scores decreased based on the bulk rna-seq datasets in Osteoarthritis.Conclusion: Our results revealed alterations in cell–cell communication among OA-related chondrocyte subtypes that were mediated by specific signaling pathways, which might be a crucial underlying mechanism associated with Osteoarthritis progression.https://www.frontiersin.org/articles/10.3389/fcell.2023.1099287/fullosteoarthritiscell-cell communicationsingle-cell transcriptomic sequencingsignaling pathwaychondrocytes |
| spellingShingle | Xin Kang Kailiang Zhang Yakang Wang Yang Zhao Yao Lu Single-cell RNA sequencing analysis of human chondrocytes reveals cell–cell communication alterations mediated by interactive signaling pathways in osteoarthritis Frontiers in Cell and Developmental Biology osteoarthritis cell-cell communication single-cell transcriptomic sequencing signaling pathway chondrocytes |
| title | Single-cell RNA sequencing analysis of human chondrocytes reveals cell–cell communication alterations mediated by interactive signaling pathways in osteoarthritis |
| title_full | Single-cell RNA sequencing analysis of human chondrocytes reveals cell–cell communication alterations mediated by interactive signaling pathways in osteoarthritis |
| title_fullStr | Single-cell RNA sequencing analysis of human chondrocytes reveals cell–cell communication alterations mediated by interactive signaling pathways in osteoarthritis |
| title_full_unstemmed | Single-cell RNA sequencing analysis of human chondrocytes reveals cell–cell communication alterations mediated by interactive signaling pathways in osteoarthritis |
| title_short | Single-cell RNA sequencing analysis of human chondrocytes reveals cell–cell communication alterations mediated by interactive signaling pathways in osteoarthritis |
| title_sort | single cell rna sequencing analysis of human chondrocytes reveals cell cell communication alterations mediated by interactive signaling pathways in osteoarthritis |
| topic | osteoarthritis cell-cell communication single-cell transcriptomic sequencing signaling pathway chondrocytes |
| url | https://www.frontiersin.org/articles/10.3389/fcell.2023.1099287/full |
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