Celastrol suppresses neovascularization in rat aortic vascular endothelial cells stimulated by inflammatory tenocytes via modulating the NLRP3 pathway
Appropriate formation of blood vessels is critical for tendon-bone healing during tendon injury, as excessive angiogenesis would exacerbate scar formation and lead to chronic pain and dysfunction. The mechanism to regulate inflammatory angiogenesis during tendon-bone healing remains to be elucidated...
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De Gruyter
2025-05-01
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| Series: | Open Medicine |
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| Online Access: | https://doi.org/10.1515/med-2024-1121 |
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| author | Yang Yong Wang Huajun Hou Huige Chen Jiwen Chen Xiaolei Zheng Hongjian Zheng Kai Ye Baofei Wu Chunhui Zheng Xiaofei Yuan Shiguo Zheng Boyuan |
| author_facet | Yang Yong Wang Huajun Hou Huige Chen Jiwen Chen Xiaolei Zheng Hongjian Zheng Kai Ye Baofei Wu Chunhui Zheng Xiaofei Yuan Shiguo Zheng Boyuan |
| author_sort | Yang Yong |
| collection | DOAJ |
| description | Appropriate formation of blood vessels is critical for tendon-bone healing during tendon injury, as excessive angiogenesis would exacerbate scar formation and lead to chronic pain and dysfunction. The mechanism to regulate inflammatory angiogenesis during tendon-bone healing remains to be elucidated. Here, we utilized lipopolysaccharide (LPS) to induce tenocyte inflammation and applied the conditioned medium from inflammatory tenocytes to treat rat aortic vascular endothelial cells (RAOECs). The results that indicated LPS treatment significantly induced the mRNA and protein upregulation of NLRP3, tumor necrosis factor α, IL-1β, and vascular endothelial growth factor A (VEGFA), as well as the secretion of VEGFA. Furthermore, the conditioned medium stimulated RAOEC angiogenesis. Celastrol, a quinone-methylated triterpenoid from Tripterygium wilfordii, has been reported to treat osteoarthritis. Here, celastrol could suppress LPS-induced upregulation of NLRP3 and IL-1β, and the secretion of VEGFA. Celastrol treatment also suppressed the conditioned medium-induced angiogenesis in RAOEC. Moreover, we established a rotator cuff tear rat model to stimulate tendon injury. Celastrol administration at the lesion significantly promoted tendon healing and functional recovery in injured mice by regulating NLRP3 and VEGFA levels. Taken together, these data suggest that the inflammation-induced tenocyte injury leads to angiogenesis, and that celastrol administration could suppress the inflammatory tenocyte-induced angiogenesis to promote tendon-bone healing via the NLRP3 pathway. |
| format | Article |
| id | doaj-art-1a7871f8aa7c4f95b26c30ccd39b6b6c |
| institution | OA Journals |
| issn | 2391-5463 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | De Gruyter |
| record_format | Article |
| series | Open Medicine |
| spelling | doaj-art-1a7871f8aa7c4f95b26c30ccd39b6b6c2025-08-20T01:52:14ZengDe GruyterOpen Medicine2391-54632025-05-0120112334210.1515/med-2024-1121Celastrol suppresses neovascularization in rat aortic vascular endothelial cells stimulated by inflammatory tenocytes via modulating the NLRP3 pathwayYang Yong0Wang Huajun1Hou Huige2Chen Jiwen3Chen Xiaolei4Zheng Hongjian5Zheng Kai6Ye Baofei7Wu Chunhui8Zheng Xiaofei9Yuan Shiguo10Zheng Boyuan11Department of Orthopedics, The Affiliated Shunde Hospital of Jinan University, Foshan, Guangdong Province, ChinaDepartment of Sports Medicine, The First Affiliated Hospital, Guangdong Provincial Key Laboratory of Speed Capability, The Guangzhou Key Laboratory of Precision Orthopedics and Regenerative Medicine, Jinan University, 510630, Guangzhou, ChinaDepartment of Sports Medicine, The First Affiliated Hospital, Guangdong Provincial Key Laboratory of Speed Capability, The Guangzhou Key Laboratory of Precision Orthopedics and Regenerative Medicine, Jinan University, 510630, Guangzhou, ChinaDepartment of Orthopedics, The Affiliated Shunde Hospital of Jinan University, Foshan, Guangdong Province, ChinaDepartment of Orthopedics, The Affiliated Shunde Hospital of Jinan University, Foshan, Guangdong Province, ChinaDepartment of Orthopedics, The Affiliated Shunde Hospital of Jinan University, Foshan, Guangdong Province, ChinaDepartment of Orthopaedic, Hainan Hospital, Guangdong Provincial Hospital of Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou, ChinaDepartment of Orthopaedic, Hainan Hospital, Guangdong Provincial Hospital of Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou, ChinaDepartment of Orthopedics, The Affiliated Shunde Hospital of Jinan University, Foshan, Guangdong Province, ChinaDepartment of Sports Medicine, The First Affiliated Hospital, Guangdong Provincial Key Laboratory of Speed Capability, The Guangzhou Key Laboratory of Precision Orthopedics and Regenerative Medicine, Jinan University, 510630, Guangzhou, ChinaDepartment of Orthopaedic, Hainan Hospital, Guangdong Provincial Hospital of Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou, ChinaDepartment of Sports Medicine, The First Affiliated Hospital, Guangdong Provincial Key Laboratory of Speed Capability, The Guangzhou Key Laboratory of Precision Orthopedics and Regenerative Medicine, Jinan University, 510630, Guangzhou, ChinaAppropriate formation of blood vessels is critical for tendon-bone healing during tendon injury, as excessive angiogenesis would exacerbate scar formation and lead to chronic pain and dysfunction. The mechanism to regulate inflammatory angiogenesis during tendon-bone healing remains to be elucidated. Here, we utilized lipopolysaccharide (LPS) to induce tenocyte inflammation and applied the conditioned medium from inflammatory tenocytes to treat rat aortic vascular endothelial cells (RAOECs). The results that indicated LPS treatment significantly induced the mRNA and protein upregulation of NLRP3, tumor necrosis factor α, IL-1β, and vascular endothelial growth factor A (VEGFA), as well as the secretion of VEGFA. Furthermore, the conditioned medium stimulated RAOEC angiogenesis. Celastrol, a quinone-methylated triterpenoid from Tripterygium wilfordii, has been reported to treat osteoarthritis. Here, celastrol could suppress LPS-induced upregulation of NLRP3 and IL-1β, and the secretion of VEGFA. Celastrol treatment also suppressed the conditioned medium-induced angiogenesis in RAOEC. Moreover, we established a rotator cuff tear rat model to stimulate tendon injury. Celastrol administration at the lesion significantly promoted tendon healing and functional recovery in injured mice by regulating NLRP3 and VEGFA levels. Taken together, these data suggest that the inflammation-induced tenocyte injury leads to angiogenesis, and that celastrol administration could suppress the inflammatory tenocyte-induced angiogenesis to promote tendon-bone healing via the NLRP3 pathway.https://doi.org/10.1515/med-2024-1121celastrolneovascularizationangiogenesisinflammationtenocytesnlrp3rotator cuff tear |
| spellingShingle | Yang Yong Wang Huajun Hou Huige Chen Jiwen Chen Xiaolei Zheng Hongjian Zheng Kai Ye Baofei Wu Chunhui Zheng Xiaofei Yuan Shiguo Zheng Boyuan Celastrol suppresses neovascularization in rat aortic vascular endothelial cells stimulated by inflammatory tenocytes via modulating the NLRP3 pathway Open Medicine celastrol neovascularization angiogenesis inflammation tenocytes nlrp3 rotator cuff tear |
| title | Celastrol suppresses neovascularization in rat aortic vascular endothelial cells stimulated by inflammatory tenocytes via modulating the NLRP3 pathway |
| title_full | Celastrol suppresses neovascularization in rat aortic vascular endothelial cells stimulated by inflammatory tenocytes via modulating the NLRP3 pathway |
| title_fullStr | Celastrol suppresses neovascularization in rat aortic vascular endothelial cells stimulated by inflammatory tenocytes via modulating the NLRP3 pathway |
| title_full_unstemmed | Celastrol suppresses neovascularization in rat aortic vascular endothelial cells stimulated by inflammatory tenocytes via modulating the NLRP3 pathway |
| title_short | Celastrol suppresses neovascularization in rat aortic vascular endothelial cells stimulated by inflammatory tenocytes via modulating the NLRP3 pathway |
| title_sort | celastrol suppresses neovascularization in rat aortic vascular endothelial cells stimulated by inflammatory tenocytes via modulating the nlrp3 pathway |
| topic | celastrol neovascularization angiogenesis inflammation tenocytes nlrp3 rotator cuff tear |
| url | https://doi.org/10.1515/med-2024-1121 |
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