Knockdown of LncRNA H19 inhibits vascularization and endochondral ossification via the MiRNA-21a-5p-Smad7/p-Smad2/3 pathway in fracture repair
Abstract The biological process of fracture repair involves inflammation, vascularization, endochondral ossification, and cartilage production. Long non-coding RNAs (lncRNAs) are essential for the growth and maintenance of the skeleton. In this study, the role of the long non-coding RNA H19 in endoc...
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Nature Portfolio
2025-07-01
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| Online Access: | https://doi.org/10.1038/s41598-025-11300-7 |
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| author | Qiuyue Sun Chen Zhang Bowen Chen Junyi Liao Aowen Bao Chen Zhao Hong Chen Dawei He Wei Huang Guangming Dai |
| author_facet | Qiuyue Sun Chen Zhang Bowen Chen Junyi Liao Aowen Bao Chen Zhao Hong Chen Dawei He Wei Huang Guangming Dai |
| author_sort | Qiuyue Sun |
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| description | Abstract The biological process of fracture repair involves inflammation, vascularization, endochondral ossification, and cartilage production. Long non-coding RNAs (lncRNAs) are essential for the growth and maintenance of the skeleton. In this study, the role of the long non-coding RNA H19 in endochondral ossification during fracture repair was investigated. We examined H19 expression in the contexts of skeletal development and fracture repair and found that hypertrophic chondrocytes, growing endochondral bone spongiosa, and cortical bone exhibit H19 expression. H19 expression in cortical bone was similar to that in skeletal muscle, suggesting a potential role in bone development regulation. Inhibiting H19 near fractures in a mouse model resulted in disruption of vascularization and delayed endochondral ossification, ultimately leading to delayed fracture union. Importantly, H19 inhibition had no impact on the formation of the cartilaginous callus, indicating its specific role in vascularization and ossification. Further analysis revealed that H19 reduced miR-21a-5p’s inhibition of smad7 by functioning as a sponge for miR-21a-5p. H19 silencing led to a decrease in Smad7 expression and a rise in Smad2/3 phosphorylation, and delayed both ossification and vascularization. In conclusion, H19 influences bone remodeling and fracture healing by modulating the miR-21a-5p-smad7-TGFβ-smad2/3 axis, presenting therapeutic potential for fracture repair. |
| format | Article |
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| institution | Kabale University |
| issn | 2045-2322 |
| language | English |
| publishDate | 2025-07-01 |
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| spelling | doaj-art-dbdd4cdf510f4055b8d442851f383dba2025-08-20T03:46:07ZengNature PortfolioScientific Reports2045-23222025-07-0115111710.1038/s41598-025-11300-7Knockdown of LncRNA H19 inhibits vascularization and endochondral ossification via the MiRNA-21a-5p-Smad7/p-Smad2/3 pathway in fracture repairQiuyue Sun0Chen Zhang1Bowen Chen2Junyi Liao3Aowen Bao4Chen Zhao5Hong Chen6Dawei He7Wei Huang8Guangming Dai9Department of Orthopedics, Children’s Hospital of Chongqing Medical University, National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing Key Laboratory of Structural Birth Defect and ReconstructionVIP Medical Center, The First Affiliated Hospital of Chongqing Medical UniversityDepartment of Orthopedics, The First Affiliated Hospital of Chongqing Medical UniversityDepartment of Orthopedics, The First Affiliated Hospital of Chongqing Medical UniversityDepartment of Orthopedics, Children’s Hospital of Chongqing Medical University, National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing Key Laboratory of Structural Birth Defect and ReconstructionDepartment of Orthopedics, The First Affiliated Hospital of Chongqing Medical UniversityDepartment of Orthopedics, The First Affiliated Hospital of Chongqing Medical UniversityDepartment of Urology, Children’s Hospital of Chongqing Medical University, National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, the Laboratory of Targeted Delivery of Traditional Chinese MedicineDepartment of Orthopedics, The First Affiliated Hospital of Chongqing Medical UniversityDepartment of Orthopedics, Children’s Hospital of Chongqing Medical University, National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing Key Laboratory of Structural Birth Defect and ReconstructionAbstract The biological process of fracture repair involves inflammation, vascularization, endochondral ossification, and cartilage production. Long non-coding RNAs (lncRNAs) are essential for the growth and maintenance of the skeleton. In this study, the role of the long non-coding RNA H19 in endochondral ossification during fracture repair was investigated. We examined H19 expression in the contexts of skeletal development and fracture repair and found that hypertrophic chondrocytes, growing endochondral bone spongiosa, and cortical bone exhibit H19 expression. H19 expression in cortical bone was similar to that in skeletal muscle, suggesting a potential role in bone development regulation. Inhibiting H19 near fractures in a mouse model resulted in disruption of vascularization and delayed endochondral ossification, ultimately leading to delayed fracture union. Importantly, H19 inhibition had no impact on the formation of the cartilaginous callus, indicating its specific role in vascularization and ossification. Further analysis revealed that H19 reduced miR-21a-5p’s inhibition of smad7 by functioning as a sponge for miR-21a-5p. H19 silencing led to a decrease in Smad7 expression and a rise in Smad2/3 phosphorylation, and delayed both ossification and vascularization. In conclusion, H19 influences bone remodeling and fracture healing by modulating the miR-21a-5p-smad7-TGFβ-smad2/3 axis, presenting therapeutic potential for fracture repair.https://doi.org/10.1038/s41598-025-11300-7Fracture repairVascularizationEndochondral ossificationLong non-coding RNA H19miR-21a-5psmad7 |
| spellingShingle | Qiuyue Sun Chen Zhang Bowen Chen Junyi Liao Aowen Bao Chen Zhao Hong Chen Dawei He Wei Huang Guangming Dai Knockdown of LncRNA H19 inhibits vascularization and endochondral ossification via the MiRNA-21a-5p-Smad7/p-Smad2/3 pathway in fracture repair Scientific Reports Fracture repair Vascularization Endochondral ossification Long non-coding RNA H19 miR-21a-5p smad7 |
| title | Knockdown of LncRNA H19 inhibits vascularization and endochondral ossification via the MiRNA-21a-5p-Smad7/p-Smad2/3 pathway in fracture repair |
| title_full | Knockdown of LncRNA H19 inhibits vascularization and endochondral ossification via the MiRNA-21a-5p-Smad7/p-Smad2/3 pathway in fracture repair |
| title_fullStr | Knockdown of LncRNA H19 inhibits vascularization and endochondral ossification via the MiRNA-21a-5p-Smad7/p-Smad2/3 pathway in fracture repair |
| title_full_unstemmed | Knockdown of LncRNA H19 inhibits vascularization and endochondral ossification via the MiRNA-21a-5p-Smad7/p-Smad2/3 pathway in fracture repair |
| title_short | Knockdown of LncRNA H19 inhibits vascularization and endochondral ossification via the MiRNA-21a-5p-Smad7/p-Smad2/3 pathway in fracture repair |
| title_sort | knockdown of lncrna h19 inhibits vascularization and endochondral ossification via the mirna 21a 5p smad7 p smad2 3 pathway in fracture repair |
| topic | Fracture repair Vascularization Endochondral ossification Long non-coding RNA H19 miR-21a-5p smad7 |
| url | https://doi.org/10.1038/s41598-025-11300-7 |
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