Single-cell transcriptomics reveals novel chondrocyte and osteoblast subtypes and their role in knee osteoarthritis pathogenesis
Abstract Research on treating knee osteoarthritis (KOA) is becoming more challenging due to a growing number of younger patients being affected. The pathogenesis of KOA is complex for being a multifactorial disease affecting the entire joint, with remodeling of subchondral bone playing a key role in...
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| Format: | Article |
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Nature Publishing Group
2025-02-01
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| Series: | Signal Transduction and Targeted Therapy |
| Online Access: | https://doi.org/10.1038/s41392-025-02136-8 |
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| author | Yuan Liu Wacili Da Ming-Jie Xu Chao-Xin Xiao Tao Deng Sheng-Liang Zhou Xiao-Ting Chen Yao-Jia Zhou Li Tang Yong Nie Yi Zeng Hui-Qi Xie Bin Shen |
| author_facet | Yuan Liu Wacili Da Ming-Jie Xu Chao-Xin Xiao Tao Deng Sheng-Liang Zhou Xiao-Ting Chen Yao-Jia Zhou Li Tang Yong Nie Yi Zeng Hui-Qi Xie Bin Shen |
| author_sort | Yuan Liu |
| collection | DOAJ |
| description | Abstract Research on treating knee osteoarthritis (KOA) is becoming more challenging due to a growing number of younger patients being affected. The pathogenesis of KOA is complex for being a multifactorial disease affecting the entire joint, with remodeling of subchondral bone playing a key role in the degeneration of the overlying cartilage. Therefore, this study constructed a bipedal postmenopausal KOA mouse model to better understand how the interplay between subchondral bone remodeling and cartilage degeneration contributes to KOA development. A single-cell atlas of the osteochondral composite tissue was established. Furthermore, three novel subtypes of chondrocytes, including Smoc2 + angiogenic chondrocytes, Angptl7 + angiogenic chondrocytes, and Col1a1 + osteogenic chondrocytes, were identified in femoral condyles of KOA mice. In addition, the Angptl7 + chondrocytes promoted angiogenesis in the subchondral bone of KOA mice by interacting with endothelial cells via the FGF2-FGFR2 signaling pathway. The number of H-type vessels was increased in the subchondral bone, recruiting osteoprogenitor cells and facilitating osteogenesis in KOA mice. Sparc + osteoblasts have negatively regulated bone mineralization and osteoblastic differentiation, aggravated the pathological remodeling of subchondral bone, and promoted the progression of KOA. The above findings have offered new targets and opened up an avenue for the therapeutic intervention of KOA. |
| format | Article |
| id | doaj-art-8f56036aecb94f55af10a9334fc7a0a3 |
| institution | Kabale University |
| issn | 2059-3635 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | Signal Transduction and Targeted Therapy |
| spelling | doaj-art-8f56036aecb94f55af10a9334fc7a0a32025-02-09T12:56:26ZengNature Publishing GroupSignal Transduction and Targeted Therapy2059-36352025-02-0110111710.1038/s41392-025-02136-8Single-cell transcriptomics reveals novel chondrocyte and osteoblast subtypes and their role in knee osteoarthritis pathogenesisYuan Liu0Wacili Da1Ming-Jie Xu2Chao-Xin Xiao3Tao Deng4Sheng-Liang Zhou5Xiao-Ting Chen6Yao-Jia Zhou7Li Tang8Yong Nie9Yi Zeng10Hui-Qi Xie11Bin Shen12Department of Orthopedic Surgery and Orthopedic Research Institute, West China Hospital, Sichuan UniversityDepartment of Orthopedic Surgery and Orthopedic Research Institute, West China Hospital, Sichuan UniversityDepartment of Orthopedic Surgery and Orthopedic Research Institute, West China Hospital, Sichuan UniversityStem Cell and Tissue Engineering Research Center, State Key Laboratory of Biotherapy, West China Hospital, Sichuan UniversitySchool of Mechanical Engineering, Sichuan UniversityDepartment of Orthopedic Surgery and Orthopedic Research Institute, West China Hospital, Sichuan UniversityAnimal Laboratory Center, West China Hospital, Sichuan UniversityAnimal Laboratory Center, West China Hospital, Sichuan UniversityStem Cell and Tissue Engineering Research Center, State Key Laboratory of Biotherapy, West China Hospital, Sichuan UniversityDepartment of Orthopedic Surgery and Orthopedic Research Institute, West China Hospital, Sichuan UniversityDepartment of Orthopedic Surgery and Orthopedic Research Institute, West China Hospital, Sichuan UniversityDepartment of Orthopedic Surgery and Orthopedic Research Institute, West China Hospital, Sichuan UniversityDepartment of Orthopedic Surgery and Orthopedic Research Institute, West China Hospital, Sichuan UniversityAbstract Research on treating knee osteoarthritis (KOA) is becoming more challenging due to a growing number of younger patients being affected. The pathogenesis of KOA is complex for being a multifactorial disease affecting the entire joint, with remodeling of subchondral bone playing a key role in the degeneration of the overlying cartilage. Therefore, this study constructed a bipedal postmenopausal KOA mouse model to better understand how the interplay between subchondral bone remodeling and cartilage degeneration contributes to KOA development. A single-cell atlas of the osteochondral composite tissue was established. Furthermore, three novel subtypes of chondrocytes, including Smoc2 + angiogenic chondrocytes, Angptl7 + angiogenic chondrocytes, and Col1a1 + osteogenic chondrocytes, were identified in femoral condyles of KOA mice. In addition, the Angptl7 + chondrocytes promoted angiogenesis in the subchondral bone of KOA mice by interacting with endothelial cells via the FGF2-FGFR2 signaling pathway. The number of H-type vessels was increased in the subchondral bone, recruiting osteoprogenitor cells and facilitating osteogenesis in KOA mice. Sparc + osteoblasts have negatively regulated bone mineralization and osteoblastic differentiation, aggravated the pathological remodeling of subchondral bone, and promoted the progression of KOA. The above findings have offered new targets and opened up an avenue for the therapeutic intervention of KOA.https://doi.org/10.1038/s41392-025-02136-8 |
| spellingShingle | Yuan Liu Wacili Da Ming-Jie Xu Chao-Xin Xiao Tao Deng Sheng-Liang Zhou Xiao-Ting Chen Yao-Jia Zhou Li Tang Yong Nie Yi Zeng Hui-Qi Xie Bin Shen Single-cell transcriptomics reveals novel chondrocyte and osteoblast subtypes and their role in knee osteoarthritis pathogenesis Signal Transduction and Targeted Therapy |
| title | Single-cell transcriptomics reveals novel chondrocyte and osteoblast subtypes and their role in knee osteoarthritis pathogenesis |
| title_full | Single-cell transcriptomics reveals novel chondrocyte and osteoblast subtypes and their role in knee osteoarthritis pathogenesis |
| title_fullStr | Single-cell transcriptomics reveals novel chondrocyte and osteoblast subtypes and their role in knee osteoarthritis pathogenesis |
| title_full_unstemmed | Single-cell transcriptomics reveals novel chondrocyte and osteoblast subtypes and their role in knee osteoarthritis pathogenesis |
| title_short | Single-cell transcriptomics reveals novel chondrocyte and osteoblast subtypes and their role in knee osteoarthritis pathogenesis |
| title_sort | single cell transcriptomics reveals novel chondrocyte and osteoblast subtypes and their role in knee osteoarthritis pathogenesis |
| url | https://doi.org/10.1038/s41392-025-02136-8 |
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