Loss of intraflagellar transport 140 in osteoblasts cripples bone fracture healing
The indispensability of primary cilia in skeletal development has been widely recognized. We have previously shown that intraflagellar transport 140 (IFT140), a protein component of a bidirectional intraflagellar transport system required for ciliary function, controls bone development and dentinoge...
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KeAi Communications Co. Ltd.
2025-07-01
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| Series: | Fundamental Research |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2667325822003715 |
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| author | Qiqi Fan Xuekui Wang Mengqi Zhou Yubei Chen Dike Tao Songxi Rong Shuang Zhou Hui Xue Yao Sun |
| author_facet | Qiqi Fan Xuekui Wang Mengqi Zhou Yubei Chen Dike Tao Songxi Rong Shuang Zhou Hui Xue Yao Sun |
| author_sort | Qiqi Fan |
| collection | DOAJ |
| description | The indispensability of primary cilia in skeletal development has been widely recognized. We have previously shown that intraflagellar transport 140 (IFT140), a protein component of a bidirectional intraflagellar transport system required for ciliary function, controls bone development and dentinogenesis. However, it remains unknown whether IFT140 functionally contributes to bone fracture rehabilitation. Here an osteotomy-induced femoral fracture model was generated in Ift140-transgenic (Ift140-TG) and osteoblast-specific Ift140-conditional knockout (Ift140-cKO) mice. Micro-computed tomography, osteogenic induction, qualitative polymerase chain reaction, and toluidine blue and safranin O/fast green staining assays were used to characterize the dynamics of bone fracture healing from various perspectives. We found that IFT140 was relatively enriched in the bone callus and decreased in fracture-susceptible aged, or diabetic bones. Ift140-cKO mice had impaired osteogenic differentiation from bone mesenchymal stem cells, lower bone mass, and delayed fracture closure, whereas Ift140-TG mice had promising healing outcomes. Overall, our findings demonstrated for the first time that IFT140 has a beneficial role in fracture repair. Future investigation of the primary cilium in the context of aging and osteoporosis would certainly benefit patients at high risk of bone fractures. |
| format | Article |
| id | doaj-art-e31cfcad3b3e42ec85a48ba5a220f793 |
| institution | DOAJ |
| issn | 2667-3258 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | KeAi Communications Co. Ltd. |
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| series | Fundamental Research |
| spelling | doaj-art-e31cfcad3b3e42ec85a48ba5a220f7932025-08-20T02:48:43ZengKeAi Communications Co. Ltd.Fundamental Research2667-32582025-07-01541795180310.1016/j.fmre.2022.09.006Loss of intraflagellar transport 140 in osteoblasts cripples bone fracture healingQiqi Fan0Xuekui Wang1Mengqi Zhou2Yubei Chen3Dike Tao4Songxi Rong5Shuang Zhou6Hui Xue7Yao Sun8Department of Oral Implantology, Shanghai Engineering Research Center of Tooth Restoration and Regeneration, Stomatological Hospital and Dental School of Tongji University, Shanghai 200072, China; Department of Stomatology, Huashan Hospital of Fudan University, Shanghai 200040, ChinaDepartment of Oral Implantology, Shanghai Engineering Research Center of Tooth Restoration and Regeneration, Stomatological Hospital and Dental School of Tongji University, Shanghai 200072, ChinaDepartment of Oral Implantology, Shanghai Engineering Research Center of Tooth Restoration and Regeneration, Stomatological Hospital and Dental School of Tongji University, Shanghai 200072, China; Department of Endodontics, Shanghai Stomatological Hospital and Oral Biomedical Engineering Laboratory, Shanghai Stomatological Hospital, Fudan University, Shanghai 200001, ChinaDepartment of Oral Implantology, Shanghai Engineering Research Center of Tooth Restoration and Regeneration, Stomatological Hospital and Dental School of Tongji University, Shanghai 200072, ChinaDepartment of Oral Implantology, Shanghai Engineering Research Center of Tooth Restoration and Regeneration, Stomatological Hospital and Dental School of Tongji University, Shanghai 200072, ChinaDepartment of Oral Implantology, Shanghai Engineering Research Center of Tooth Restoration and Regeneration, Stomatological Hospital and Dental School of Tongji University, Shanghai 200072, ChinaDepartment of Oral Implantology, Shanghai Engineering Research Center of Tooth Restoration and Regeneration, Stomatological Hospital and Dental School of Tongji University, Shanghai 200072, China; Department of Stomatology, Children's Hospital of Soochow University, Suzhou 215003, ChinaDepartment of Oral Implantology, Shanghai Engineering Research Center of Tooth Restoration and Regeneration, Stomatological Hospital and Dental School of Tongji University, Shanghai 200072, China; Department of Stomatology, The First Affiliated Hospital of Qiqihar Medical University, Qiqihar 161041, ChinaDepartment of Oral Implantology, Shanghai Engineering Research Center of Tooth Restoration and Regeneration, Stomatological Hospital and Dental School of Tongji University, Shanghai 200072, China; Corresponding author.The indispensability of primary cilia in skeletal development has been widely recognized. We have previously shown that intraflagellar transport 140 (IFT140), a protein component of a bidirectional intraflagellar transport system required for ciliary function, controls bone development and dentinogenesis. However, it remains unknown whether IFT140 functionally contributes to bone fracture rehabilitation. Here an osteotomy-induced femoral fracture model was generated in Ift140-transgenic (Ift140-TG) and osteoblast-specific Ift140-conditional knockout (Ift140-cKO) mice. Micro-computed tomography, osteogenic induction, qualitative polymerase chain reaction, and toluidine blue and safranin O/fast green staining assays were used to characterize the dynamics of bone fracture healing from various perspectives. We found that IFT140 was relatively enriched in the bone callus and decreased in fracture-susceptible aged, or diabetic bones. Ift140-cKO mice had impaired osteogenic differentiation from bone mesenchymal stem cells, lower bone mass, and delayed fracture closure, whereas Ift140-TG mice had promising healing outcomes. Overall, our findings demonstrated for the first time that IFT140 has a beneficial role in fracture repair. Future investigation of the primary cilium in the context of aging and osteoporosis would certainly benefit patients at high risk of bone fractures.http://www.sciencedirect.com/science/article/pii/S2667325822003715Primary CiliaIntraflagellar Transport 140Bone fractureOsteoblastsBone Mesenchymal Stem Cells |
| spellingShingle | Qiqi Fan Xuekui Wang Mengqi Zhou Yubei Chen Dike Tao Songxi Rong Shuang Zhou Hui Xue Yao Sun Loss of intraflagellar transport 140 in osteoblasts cripples bone fracture healing Fundamental Research Primary Cilia Intraflagellar Transport 140 Bone fracture Osteoblasts Bone Mesenchymal Stem Cells |
| title | Loss of intraflagellar transport 140 in osteoblasts cripples bone fracture healing |
| title_full | Loss of intraflagellar transport 140 in osteoblasts cripples bone fracture healing |
| title_fullStr | Loss of intraflagellar transport 140 in osteoblasts cripples bone fracture healing |
| title_full_unstemmed | Loss of intraflagellar transport 140 in osteoblasts cripples bone fracture healing |
| title_short | Loss of intraflagellar transport 140 in osteoblasts cripples bone fracture healing |
| title_sort | loss of intraflagellar transport 140 in osteoblasts cripples bone fracture healing |
| topic | Primary Cilia Intraflagellar Transport 140 Bone fracture Osteoblasts Bone Mesenchymal Stem Cells |
| url | http://www.sciencedirect.com/science/article/pii/S2667325822003715 |
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