CD73 alleviates osteoarthritis by maintaining anabolism and suppressing catabolism of chondrocytes extracellular matrix
Background: Osteoarthritis (OA) is the most common degenerative joint disease, with articular cartilage degeneration as primary manifestation. Intra-articular injection of exogenous liposomal adenosine in mice knee has been shown to alleviate OA progression. However, the role of CD73, the rate-limit...
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Elsevier
2024-11-01
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| Series: | Journal of Orthopaedic Translation |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2214031X24001013 |
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| author | Hu Guo Zhongyang Lv Maochun Wang Weitong Li Ya Xie Zizheng Liu Fufei Chen Ruiyang Jiang Yuan Liu Rui Wu Jiawei Li Ziying Sun Guihua Tan Dongquan Shi |
| author_facet | Hu Guo Zhongyang Lv Maochun Wang Weitong Li Ya Xie Zizheng Liu Fufei Chen Ruiyang Jiang Yuan Liu Rui Wu Jiawei Li Ziying Sun Guihua Tan Dongquan Shi |
| author_sort | Hu Guo |
| collection | DOAJ |
| description | Background: Osteoarthritis (OA) is the most common degenerative joint disease, with articular cartilage degeneration as primary manifestation. Intra-articular injection of exogenous liposomal adenosine in mice knee has been shown to alleviate OA progression. However, the role of CD73, the rate-limiting enzyme of extracellular adenosine synthesis, in OA is still unknown. Methods: In this work, we explored the expression changes of adenosine-related molecules via bioinformatic analysis. In addition, the expression level of these molecules was detected in OA cartilage. We also conducted a case–control study to investigate the genetic variants of selected SNPs on genes encoded adenosine-related molecules. To further explore the function of CD73 in chondrocytes, we knocked down the expression of CD73 with small interfering RNA and overexpressed CD73 with the use of lentivirus, and detected the expression of markers for anabolism and catabolism in mouse primary chondrocytes with or without IL-1β treatment. We also conducted in vivo experiments to explore the role of CD73 in OA. Results: We found that the expression of CD73 was upregulated in OA, and the variants of SNP rs2229523 (base A to G) on NT5E (the encoding gene of CD73) were significantly higher in OA population, which might cause the amino acid encoded by this SNP change from threonine to alanine. The original helix structure in the adjacent region of amino acid encoded by SNP rs2229523 would be deconstructed after its mutation. Furthermore, we found that CD73 promoting the expression of Col2a1 but suppressing the expression of Mmp13 expression in mouse primary chondrocytes under inflammatory environment. The overexpression of CD73 attenuated bone remodeling and alleviated cartilage degeneration in DMM mice. Moreover, the physical activities were also improved in DMM mice overexpressed CD73 with the use of adeno-associated virus. Conclusions: The variants of SNP rs2229523 (base A to G) on NT5E were significantly higher in OA population, and CD73 could alleviate OA by maintaining anabolism and suppressing catabolism of chondrocytes extracellular matrix. The Translational Potential of this Article: This work showed that CD73 might be one of the biological therapeutic targets of OA, which would provide a reference for future novel treatment strategy of OA. |
| format | Article |
| id | doaj-art-0a7850d3dd9e4e9ea1aafc280e3ebe96 |
| institution | Kabale University |
| issn | 2214-031X |
| language | English |
| publishDate | 2024-11-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Journal of Orthopaedic Translation |
| spelling | doaj-art-0a7850d3dd9e4e9ea1aafc280e3ebe962024-12-05T05:20:24ZengElsevierJournal of Orthopaedic Translation2214-031X2024-11-014996106CD73 alleviates osteoarthritis by maintaining anabolism and suppressing catabolism of chondrocytes extracellular matrixHu Guo0Zhongyang Lv1Maochun Wang2Weitong Li3Ya Xie4Zizheng Liu5Fufei Chen6Ruiyang Jiang7Yuan Liu8Rui Wu9Jiawei Li10Ziying Sun11Guihua Tan12Dongquan Shi13Division of Sports Medicine and Adult Reconstructive Surgery, Department of Orthopedic Surgery, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, ChinaDivision of Sports Medicine and Adult Reconstructive Surgery, Department of Orthopedic Surgery, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, China; Department of Orthopedics, Nanjing Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, ChinaDivision of Sports Medicine and Adult Reconstructive Surgery, Department of Orthopedic Surgery, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, ChinaDivision of Sports Medicine and Adult Reconstructive Surgery, Department of Orthopedic Surgery, Nanjing Drum Tower Hospital Clinical College of Nanjing University of Chinese Medicine, Nanjing, ChinaDivision of Sports Medicine and Adult Reconstructive Surgery, Department of Orthopedic Surgery, Nanjing Drum Tower Hospital Clinical College of Nanjing University of Chinese Medicine, Nanjing, ChinaDivision of Sports Medicine and Adult Reconstructive Surgery, Department of Orthopedic Surgery, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, ChinaDivision of Sports Medicine and Adult Reconstructive Surgery, Department of Orthopedic Surgery, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, ChinaDivision of Sports Medicine and Adult Reconstructive Surgery, Department of Orthopedic Surgery, Nanjing Drum Tower Hospital Clinical College of Xuzhou Medical University, Xuzhou Medical University, Nanjing, ChinaDivision of Sports Medicine and Adult Reconstructive Surgery, Department of Orthopedic Surgery, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, ChinaDivision of Sports Medicine and Adult Reconstructive Surgery, Department of Orthopedic Surgery, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, ChinaDepartment of Orthopedic Surgery, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, ChinaDivision of Sports Medicine and Adult Reconstructive Surgery, Department of Orthopedic Surgery, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, China; Department of Orthopedics, Nanjing Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, ChinaDivision of Sports Medicine and Adult Reconstructive Surgery, Department of Orthopedic Surgery, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, ChinaDivision of Sports Medicine and Adult Reconstructive Surgery, Department of Orthopedic Surgery, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, China; Corresponding author.Background: Osteoarthritis (OA) is the most common degenerative joint disease, with articular cartilage degeneration as primary manifestation. Intra-articular injection of exogenous liposomal adenosine in mice knee has been shown to alleviate OA progression. However, the role of CD73, the rate-limiting enzyme of extracellular adenosine synthesis, in OA is still unknown. Methods: In this work, we explored the expression changes of adenosine-related molecules via bioinformatic analysis. In addition, the expression level of these molecules was detected in OA cartilage. We also conducted a case–control study to investigate the genetic variants of selected SNPs on genes encoded adenosine-related molecules. To further explore the function of CD73 in chondrocytes, we knocked down the expression of CD73 with small interfering RNA and overexpressed CD73 with the use of lentivirus, and detected the expression of markers for anabolism and catabolism in mouse primary chondrocytes with or without IL-1β treatment. We also conducted in vivo experiments to explore the role of CD73 in OA. Results: We found that the expression of CD73 was upregulated in OA, and the variants of SNP rs2229523 (base A to G) on NT5E (the encoding gene of CD73) were significantly higher in OA population, which might cause the amino acid encoded by this SNP change from threonine to alanine. The original helix structure in the adjacent region of amino acid encoded by SNP rs2229523 would be deconstructed after its mutation. Furthermore, we found that CD73 promoting the expression of Col2a1 but suppressing the expression of Mmp13 expression in mouse primary chondrocytes under inflammatory environment. The overexpression of CD73 attenuated bone remodeling and alleviated cartilage degeneration in DMM mice. Moreover, the physical activities were also improved in DMM mice overexpressed CD73 with the use of adeno-associated virus. Conclusions: The variants of SNP rs2229523 (base A to G) on NT5E were significantly higher in OA population, and CD73 could alleviate OA by maintaining anabolism and suppressing catabolism of chondrocytes extracellular matrix. The Translational Potential of this Article: This work showed that CD73 might be one of the biological therapeutic targets of OA, which would provide a reference for future novel treatment strategy of OA.http://www.sciencedirect.com/science/article/pii/S2214031X24001013AdenosineCD73Chondrocytes extracellular matrixOsteoarthritisSingle nucleotide polymorphisms |
| spellingShingle | Hu Guo Zhongyang Lv Maochun Wang Weitong Li Ya Xie Zizheng Liu Fufei Chen Ruiyang Jiang Yuan Liu Rui Wu Jiawei Li Ziying Sun Guihua Tan Dongquan Shi CD73 alleviates osteoarthritis by maintaining anabolism and suppressing catabolism of chondrocytes extracellular matrix Journal of Orthopaedic Translation Adenosine CD73 Chondrocytes extracellular matrix Osteoarthritis Single nucleotide polymorphisms |
| title | CD73 alleviates osteoarthritis by maintaining anabolism and suppressing catabolism of chondrocytes extracellular matrix |
| title_full | CD73 alleviates osteoarthritis by maintaining anabolism and suppressing catabolism of chondrocytes extracellular matrix |
| title_fullStr | CD73 alleviates osteoarthritis by maintaining anabolism and suppressing catabolism of chondrocytes extracellular matrix |
| title_full_unstemmed | CD73 alleviates osteoarthritis by maintaining anabolism and suppressing catabolism of chondrocytes extracellular matrix |
| title_short | CD73 alleviates osteoarthritis by maintaining anabolism and suppressing catabolism of chondrocytes extracellular matrix |
| title_sort | cd73 alleviates osteoarthritis by maintaining anabolism and suppressing catabolism of chondrocytes extracellular matrix |
| topic | Adenosine CD73 Chondrocytes extracellular matrix Osteoarthritis Single nucleotide polymorphisms |
| url | http://www.sciencedirect.com/science/article/pii/S2214031X24001013 |
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