Loss of Bcl-3 delays bone fracture healing through activating NF-κB signaling in mesenchymal stem cells
Background: Bone fracture healing is a postnatal regenerative process in which fibrocartilaginous callus formation and bony callus formation are important. Bony callus formation requires osteoblastic differentiation of MSCs. Materials and methods: The formation of callus was assessed by μCT, Safrani...
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| Format: | Article |
| Language: | English |
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Elsevier
2022-07-01
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| Series: | Journal of Orthopaedic Translation |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2214031X22000729 |
| _version_ | 1829096417878081536 |
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| author | Fuxiao Wang Jiawei Guo Yili Wang Yan Hu Hao Zhang Jiao Chen Yingying Jing Liehu Cao Xiao Chen Jiacan Su |
| author_facet | Fuxiao Wang Jiawei Guo Yili Wang Yan Hu Hao Zhang Jiao Chen Yingying Jing Liehu Cao Xiao Chen Jiacan Su |
| author_sort | Fuxiao Wang |
| collection | DOAJ |
| description | Background: Bone fracture healing is a postnatal regenerative process in which fibrocartilaginous callus formation and bony callus formation are important. Bony callus formation requires osteoblastic differentiation of MSCs. Materials and methods: The formation of callus was assessed by μCT, Safranin-O, H&E and Masson trichrome staining. Osteogenesis of MSCs was analyzed by ALP staining, ARS staining, qRT-PCR and WB. And we also used IF and TOP/FOP Flash luciferase reporter to assess the nuclear translocation of PP65. Results: In this study, we found Bcl-3 showed a significant correlation with bone fracture healing. Results of μCT showed that loss of Bcl-3 delays bone fracture healing. Safranin-O, H&E and Masson trichrome staining confirmed that loss of Bcl-3 impacted the formation of cartilage and woven bone in callus. Further experiments in vitro manifested that Bcl-3-knockdown could inhibit MSCs osteoblastic differentiation through releasing the inhibition on NF-κB signaling by Co-IP, IF staining and luciferase reporter assay. Conclusions: We unveiled that loss of Bcl-3 could lead to inhibited osteogenic differentiation of MSCs via promoting PP65 nuclear translocation. The translational potential of this article: Our data demonstrated that overexpression of Bcl-3 accelerates bone fracture healing, which serves as a promising therapeutic target for bone fracture treatment. |
| first_indexed | 2024-04-11T08:56:50Z |
| format | Article |
| id | doaj.art-f4e1d3abcd4b4496bbfce2b2607c35f5 |
| institution | Directory Open Access Journal |
| issn | 2214-031X |
| language | English |
| last_indexed | 2024-04-11T08:56:50Z |
| publishDate | 2022-07-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Journal of Orthopaedic Translation |
| spelling | doaj.art-f4e1d3abcd4b4496bbfce2b2607c35f52022-12-22T04:33:17ZengElsevierJournal of Orthopaedic Translation2214-031X2022-07-01357280Loss of Bcl-3 delays bone fracture healing through activating NF-κB signaling in mesenchymal stem cellsFuxiao Wang0Jiawei Guo1Yili Wang2Yan Hu3Hao Zhang4Jiao Chen5Yingying Jing6Liehu Cao7Xiao Chen8Jiacan Su9Musculoskeletal Organoid Research Center, Institute of Translational Medicine, Shanghai University, Shanghai 200444, ChinaDepartment of Orthopedics Trauma, Shanghai Changhai Hospital, Naval Medical University, Shanghai 200433, ChinaMusculoskeletal Organoid Research Center, Institute of Translational Medicine, Shanghai University, Shanghai 200444, ChinaMusculoskeletal Organoid Research Center, Institute of Translational Medicine, Shanghai University, Shanghai 200444, ChinaDepartment of Orthopedics Trauma, Shanghai Changhai Hospital, Naval Medical University, Shanghai 200433, ChinaMusculoskeletal Organoid Research Center, Institute of Translational Medicine, Shanghai University, Shanghai 200444, ChinaMusculoskeletal Organoid Research Center, Institute of Translational Medicine, Shanghai University, Shanghai 200444, ChinaDepartment of Orthopedics, Shanghai Baoshan Luodian Hospital, Baoshan District, Shanghai 201908, China; Corresponding author.Department of Orthopedics Trauma, Shanghai Changhai Hospital, Naval Medical University, Shanghai 200433, China; Corresponding author.Musculoskeletal Organoid Research Center, Institute of Translational Medicine, Shanghai University, Shanghai 200444, China; Department of Orthopedics Trauma, Shanghai Changhai Hospital, Naval Medical University, Shanghai 200433, China; Corresponding author. Musculoskeletal Organoid Research Center, Institute of Translational Medicine, Shanghai University, Shanghai, 201901, China.Background: Bone fracture healing is a postnatal regenerative process in which fibrocartilaginous callus formation and bony callus formation are important. Bony callus formation requires osteoblastic differentiation of MSCs. Materials and methods: The formation of callus was assessed by μCT, Safranin-O, H&E and Masson trichrome staining. Osteogenesis of MSCs was analyzed by ALP staining, ARS staining, qRT-PCR and WB. And we also used IF and TOP/FOP Flash luciferase reporter to assess the nuclear translocation of PP65. Results: In this study, we found Bcl-3 showed a significant correlation with bone fracture healing. Results of μCT showed that loss of Bcl-3 delays bone fracture healing. Safranin-O, H&E and Masson trichrome staining confirmed that loss of Bcl-3 impacted the formation of cartilage and woven bone in callus. Further experiments in vitro manifested that Bcl-3-knockdown could inhibit MSCs osteoblastic differentiation through releasing the inhibition on NF-κB signaling by Co-IP, IF staining and luciferase reporter assay. Conclusions: We unveiled that loss of Bcl-3 could lead to inhibited osteogenic differentiation of MSCs via promoting PP65 nuclear translocation. The translational potential of this article: Our data demonstrated that overexpression of Bcl-3 accelerates bone fracture healing, which serves as a promising therapeutic target for bone fracture treatment.http://www.sciencedirect.com/science/article/pii/S2214031X22000729Bcl-3Fracture healingMesenchymal stem cellsNF-κB |
| spellingShingle | Fuxiao Wang Jiawei Guo Yili Wang Yan Hu Hao Zhang Jiao Chen Yingying Jing Liehu Cao Xiao Chen Jiacan Su Loss of Bcl-3 delays bone fracture healing through activating NF-κB signaling in mesenchymal stem cells Journal of Orthopaedic Translation Bcl-3 Fracture healing Mesenchymal stem cells NF-κB |
| title | Loss of Bcl-3 delays bone fracture healing through activating NF-κB signaling in mesenchymal stem cells |
| title_full | Loss of Bcl-3 delays bone fracture healing through activating NF-κB signaling in mesenchymal stem cells |
| title_fullStr | Loss of Bcl-3 delays bone fracture healing through activating NF-κB signaling in mesenchymal stem cells |
| title_full_unstemmed | Loss of Bcl-3 delays bone fracture healing through activating NF-κB signaling in mesenchymal stem cells |
| title_short | Loss of Bcl-3 delays bone fracture healing through activating NF-κB signaling in mesenchymal stem cells |
| title_sort | loss of bcl 3 delays bone fracture healing through activating nf κb signaling in mesenchymal stem cells |
| topic | Bcl-3 Fracture healing Mesenchymal stem cells NF-κB |
| url | http://www.sciencedirect.com/science/article/pii/S2214031X22000729 |
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