Methyltransferase Setdb1 Promotes Osteoblast Proliferation by Epigenetically Silencing Macrod2 with the Assistance of Atf7ip
Bone loss caused by mechanical unloading is a threat to prolonged space flight and human health. Epigenetic modifications play a crucial role in varied biological processes, but the mechanism of histone modification on unloading-induced bone loss has rarely been studied. Here, we discovered for the...
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| Format: | Article |
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MDPI AG
2022-08-01
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| Series: | Cells |
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| Online Access: | https://www.mdpi.com/2073-4409/11/16/2580 |
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| author | Lijun Zhang Liqun Xu Xiaoyan Zhang Ke Wang Yingjun Tan Gaozhi Li Yixuan Wang Tong Xue Quan Sun Xinsheng Cao Ge Zhang Zebing Hu Shu Zhang Fei Shi |
| author_facet | Lijun Zhang Liqun Xu Xiaoyan Zhang Ke Wang Yingjun Tan Gaozhi Li Yixuan Wang Tong Xue Quan Sun Xinsheng Cao Ge Zhang Zebing Hu Shu Zhang Fei Shi |
| author_sort | Lijun Zhang |
| collection | DOAJ |
| description | Bone loss caused by mechanical unloading is a threat to prolonged space flight and human health. Epigenetic modifications play a crucial role in varied biological processes, but the mechanism of histone modification on unloading-induced bone loss has rarely been studied. Here, we discovered for the first time that the methyltransferase Setdb1 was downregulated under the mechanical unloading both in vitro and in vivo so as to attenuate osteoblast proliferation. Furthermore, we found these interesting processes depended on the repression of Macrod2 expression triggered by Setdb1 catalyzing the formation of H3K9me3 in the promoter region. Mechanically, we revealed that Macrod2 was upregulated under mechanical unloading and suppressed osteoblast proliferation through the GSK-3β/β-catenin signaling pathway. Moreover, Atf7ip cooperatively contributed to osteoblast proliferation by changing the localization of Setdb1 under mechanical loading. In summary, this research elucidated the role of the Atf7ip/Setdb1/Macrod2 axis in osteoblast proliferation under mechanical unloading for the first time, which can be a potential protective strategy against unloading-induced bone loss. |
| first_indexed | 2024-03-09T04:36:40Z |
| format | Article |
| id | doaj.art-395ca681bda14c72b62d8f910b264a2d |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-09T04:36:40Z |
| publishDate | 2022-08-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-395ca681bda14c72b62d8f910b264a2d2023-12-03T13:27:19ZengMDPI AGCells2073-44092022-08-011116258010.3390/cells11162580Methyltransferase Setdb1 Promotes Osteoblast Proliferation by Epigenetically Silencing Macrod2 with the Assistance of Atf7ipLijun Zhang0Liqun Xu1Xiaoyan Zhang2Ke Wang3Yingjun Tan4Gaozhi Li5Yixuan Wang6Tong Xue7Quan Sun8Xinsheng Cao9Ge Zhang10Zebing Hu11Shu Zhang12Fei Shi13The Key Laboratory of Aerospace Medicine, Ministry of Education, Air Force Medical University, Xi’an 710032, ChinaThe Key Laboratory of Aerospace Medicine, Ministry of Education, Air Force Medical University, Xi’an 710032, ChinaThe Key Laboratory of Aerospace Medicine, Ministry of Education, Air Force Medical University, Xi’an 710032, ChinaThe Key Laboratory of Aerospace Medicine, Ministry of Education, Air Force Medical University, Xi’an 710032, ChinaState Key Laboratory of Space Medicine Fundamentals and Application, China Astronaut Research and Training Center, Beijing 100094, ChinaThe Key Laboratory of Aerospace Medicine, Ministry of Education, Air Force Medical University, Xi’an 710032, ChinaThe Key Laboratory of Aerospace Medicine, Ministry of Education, Air Force Medical University, Xi’an 710032, ChinaThe Key Laboratory of Aerospace Medicine, Ministry of Education, Air Force Medical University, Xi’an 710032, ChinaThe Key Laboratory of Aerospace Medicine, Ministry of Education, Air Force Medical University, Xi’an 710032, ChinaThe Key Laboratory of Aerospace Medicine, Ministry of Education, Air Force Medical University, Xi’an 710032, ChinaInstitute for Advancing Translational Medicine in Bone & Joint Diseases, School of Chinese Medicine, Hong Kong Baptist University, Hong Kong 999077, ChinaThe Key Laboratory of Aerospace Medicine, Ministry of Education, Air Force Medical University, Xi’an 710032, ChinaThe Key Laboratory of Aerospace Medicine, Ministry of Education, Air Force Medical University, Xi’an 710032, ChinaThe Key Laboratory of Aerospace Medicine, Ministry of Education, Air Force Medical University, Xi’an 710032, ChinaBone loss caused by mechanical unloading is a threat to prolonged space flight and human health. Epigenetic modifications play a crucial role in varied biological processes, but the mechanism of histone modification on unloading-induced bone loss has rarely been studied. Here, we discovered for the first time that the methyltransferase Setdb1 was downregulated under the mechanical unloading both in vitro and in vivo so as to attenuate osteoblast proliferation. Furthermore, we found these interesting processes depended on the repression of Macrod2 expression triggered by Setdb1 catalyzing the formation of H3K9me3 in the promoter region. Mechanically, we revealed that Macrod2 was upregulated under mechanical unloading and suppressed osteoblast proliferation through the GSK-3β/β-catenin signaling pathway. Moreover, Atf7ip cooperatively contributed to osteoblast proliferation by changing the localization of Setdb1 under mechanical loading. In summary, this research elucidated the role of the Atf7ip/Setdb1/Macrod2 axis in osteoblast proliferation under mechanical unloading for the first time, which can be a potential protective strategy against unloading-induced bone loss.https://www.mdpi.com/2073-4409/11/16/2580Setdb1cell proliferationmechanical unloadingbone loss |
| spellingShingle | Lijun Zhang Liqun Xu Xiaoyan Zhang Ke Wang Yingjun Tan Gaozhi Li Yixuan Wang Tong Xue Quan Sun Xinsheng Cao Ge Zhang Zebing Hu Shu Zhang Fei Shi Methyltransferase Setdb1 Promotes Osteoblast Proliferation by Epigenetically Silencing Macrod2 with the Assistance of Atf7ip Cells Setdb1 cell proliferation mechanical unloading bone loss |
| title | Methyltransferase Setdb1 Promotes Osteoblast Proliferation by Epigenetically Silencing Macrod2 with the Assistance of Atf7ip |
| title_full | Methyltransferase Setdb1 Promotes Osteoblast Proliferation by Epigenetically Silencing Macrod2 with the Assistance of Atf7ip |
| title_fullStr | Methyltransferase Setdb1 Promotes Osteoblast Proliferation by Epigenetically Silencing Macrod2 with the Assistance of Atf7ip |
| title_full_unstemmed | Methyltransferase Setdb1 Promotes Osteoblast Proliferation by Epigenetically Silencing Macrod2 with the Assistance of Atf7ip |
| title_short | Methyltransferase Setdb1 Promotes Osteoblast Proliferation by Epigenetically Silencing Macrod2 with the Assistance of Atf7ip |
| title_sort | methyltransferase setdb1 promotes osteoblast proliferation by epigenetically silencing macrod2 with the assistance of atf7ip |
| topic | Setdb1 cell proliferation mechanical unloading bone loss |
| url | https://www.mdpi.com/2073-4409/11/16/2580 |
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