CircRNA AFF4 induced by KDM1A promotes osteogenic differentiation through FNDC5/Irisin pathway
Abstract Background Circular RNA (circ) AFF4 was documented to regulate osteogenesis but the underlying mechanism remains to be elucidated. The preliminary study showed that circ_AFF4 may promote osteogenesis via FNDC5/Irisin. Furthermore, the online prediction tool indicated the interaction of circ...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2022-11-01
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| Series: | Molecular Medicine |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s10020-022-00557-7 |
| _version_ | 1828127926146564096 |
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| author | Ansong Liu Yong Chen Da Zhong Chenggong Wang Mi Yu Chao Liu Zhijun Yang Wenkang Chen Ke Yin |
| author_facet | Ansong Liu Yong Chen Da Zhong Chenggong Wang Mi Yu Chao Liu Zhijun Yang Wenkang Chen Ke Yin |
| author_sort | Ansong Liu |
| collection | DOAJ |
| description | Abstract Background Circular RNA (circ) AFF4 was documented to regulate osteogenesis but the underlying mechanism remains to be elucidated. The preliminary study showed that circ_AFF4 may promote osteogenesis via FNDC5/Irisin. Furthermore, the online prediction tool indicated the interaction of circ_AFF4, insulin-like growth factor-2 mRNA-binding protein 3 (IGF2BP3), FNDC5 and lysine (K)-specific demethylase 1 A (KDM1A). Therefore, this study aims to elucidate the relationships of KDM1A, circ_AFF4, IGF2BP3 and FNDC5/Irisin during osteogenesis. Methods The alkaline phosphatase (ALP) activities and osteogenic-related factors were determined using ALP and alizarin red S (ARS) staining, real-time quantitative PCR(RT-qPCR) and western blot. Immunoprecipitation (RIP), pull-down assay and fluorescence in situ hybridization (FISH) were used to examine the interactions among circ_AFF4/IGF2BP3/FNDC5. A mouse in vivo model was utilized to further confirm the regulatory effect on bone formation. Results Circ_AFF4 and KDM1A expression levels were increased during osteoinduction of BM-MSCs. Knockdown of circ_AFF4 and KDM1A significantly suppressed BM-MSC osteogenesis. We also proved that KDM1A directly bound to circ_AFF4 and FNDC5 promoter and induced circ_AFF4 and FNDC5 expression. Furthermore, circ_AFF4 enhanced the stability of FNDC5 by generating a circ_AFF4, IGF2BP3 and FNDC5 RNA-protein complex, and thereby induced Irisin and osteogenesis. The in vitro data was confirmed with in vivo model. Conclusion These findings elucidate that KDM1A induces circ_AFF4, which promotes promote osteogenesis via IGF2BP3. This study indicates that circ_AFF4 may potentially represent a critical therapeutic target for the diseases. |
| first_indexed | 2024-04-11T15:56:49Z |
| format | Article |
| id | doaj.art-70527d5a0107417987e4fa61333e7823 |
| institution | Directory Open Access Journal |
| issn | 1076-1551 1528-3658 |
| language | English |
| last_indexed | 2024-04-11T15:56:49Z |
| publishDate | 2022-11-01 |
| publisher | BMC |
| record_format | Article |
| series | Molecular Medicine |
| spelling | doaj.art-70527d5a0107417987e4fa61333e78232022-12-22T04:15:08ZengBMCMolecular Medicine1076-15511528-36582022-11-0128111510.1186/s10020-022-00557-7CircRNA AFF4 induced by KDM1A promotes osteogenic differentiation through FNDC5/Irisin pathwayAnsong Liu0Yong Chen1Da Zhong2Chenggong Wang3Mi Yu4Chao Liu5Zhijun Yang6Wenkang Chen7Ke Yin8The First Affiliated Hospital, Department of Orthopedics, Hengyang Medical School, University of South ChinaThe First Affiliated Hospital, Department of Spine, Hengyang Medical School, University of South ChinaDepartment of Orthopedics, Xiangya Hospital, Central South UniversityDepartment of Orthopedics, Xiangya Hospital, Central South UniversityHengyang Medical School, University of South ChinaThe First Affiliated Hospital, Department of Orthopedics, Hengyang Medical School, University of South ChinaThe First Affiliated Hospital, Department of Orthopedics, Hengyang Medical School, University of South ChinaThe First Affiliated Hospital, Department of Orthopedics, Hengyang Medical School, University of South ChinaThe First Affiliated Hospital, Department of Orthopedics, Hengyang Medical School, University of South ChinaAbstract Background Circular RNA (circ) AFF4 was documented to regulate osteogenesis but the underlying mechanism remains to be elucidated. The preliminary study showed that circ_AFF4 may promote osteogenesis via FNDC5/Irisin. Furthermore, the online prediction tool indicated the interaction of circ_AFF4, insulin-like growth factor-2 mRNA-binding protein 3 (IGF2BP3), FNDC5 and lysine (K)-specific demethylase 1 A (KDM1A). Therefore, this study aims to elucidate the relationships of KDM1A, circ_AFF4, IGF2BP3 and FNDC5/Irisin during osteogenesis. Methods The alkaline phosphatase (ALP) activities and osteogenic-related factors were determined using ALP and alizarin red S (ARS) staining, real-time quantitative PCR(RT-qPCR) and western blot. Immunoprecipitation (RIP), pull-down assay and fluorescence in situ hybridization (FISH) were used to examine the interactions among circ_AFF4/IGF2BP3/FNDC5. A mouse in vivo model was utilized to further confirm the regulatory effect on bone formation. Results Circ_AFF4 and KDM1A expression levels were increased during osteoinduction of BM-MSCs. Knockdown of circ_AFF4 and KDM1A significantly suppressed BM-MSC osteogenesis. We also proved that KDM1A directly bound to circ_AFF4 and FNDC5 promoter and induced circ_AFF4 and FNDC5 expression. Furthermore, circ_AFF4 enhanced the stability of FNDC5 by generating a circ_AFF4, IGF2BP3 and FNDC5 RNA-protein complex, and thereby induced Irisin and osteogenesis. The in vitro data was confirmed with in vivo model. Conclusion These findings elucidate that KDM1A induces circ_AFF4, which promotes promote osteogenesis via IGF2BP3. This study indicates that circ_AFF4 may potentially represent a critical therapeutic target for the diseases.https://doi.org/10.1186/s10020-022-00557-7Circular RNA AFF4KDM1AOsteogenic differentiationFNDC5Irisin |
| spellingShingle | Ansong Liu Yong Chen Da Zhong Chenggong Wang Mi Yu Chao Liu Zhijun Yang Wenkang Chen Ke Yin CircRNA AFF4 induced by KDM1A promotes osteogenic differentiation through FNDC5/Irisin pathway Molecular Medicine Circular RNA AFF4 KDM1A Osteogenic differentiation FNDC5 Irisin |
| title | CircRNA AFF4 induced by KDM1A promotes osteogenic differentiation through FNDC5/Irisin pathway |
| title_full | CircRNA AFF4 induced by KDM1A promotes osteogenic differentiation through FNDC5/Irisin pathway |
| title_fullStr | CircRNA AFF4 induced by KDM1A promotes osteogenic differentiation through FNDC5/Irisin pathway |
| title_full_unstemmed | CircRNA AFF4 induced by KDM1A promotes osteogenic differentiation through FNDC5/Irisin pathway |
| title_short | CircRNA AFF4 induced by KDM1A promotes osteogenic differentiation through FNDC5/Irisin pathway |
| title_sort | circrna aff4 induced by kdm1a promotes osteogenic differentiation through fndc5 irisin pathway |
| topic | Circular RNA AFF4 KDM1A Osteogenic differentiation FNDC5 Irisin |
| url | https://doi.org/10.1186/s10020-022-00557-7 |
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