Dusp1 in osteolytic diseases-mechanisms and therapeutic potential
Abstract Osteolytic diseases are a significant and escalating global public health issue, driven by the acceleration of population aging and the rising incidence of degenerative, metabolic, and neoplastic diseases. The primary therapeutic strategy for osteolytic diseases is to suppress the bone reso...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2025-07-01
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| Series: | Scientific Reports |
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| Online Access: | https://doi.org/10.1038/s41598-025-05142-6 |
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| author | Boyu Liu Ming Lei Baicheng Wan Yanbing Feng Yilin Teng Deshuang Xi Shou Chen Gaofeng Zeng Shaohui Zong |
| author_facet | Boyu Liu Ming Lei Baicheng Wan Yanbing Feng Yilin Teng Deshuang Xi Shou Chen Gaofeng Zeng Shaohui Zong |
| author_sort | Boyu Liu |
| collection | DOAJ |
| description | Abstract Osteolytic diseases are a significant and escalating global public health issue, driven by the acceleration of population aging and the rising incidence of degenerative, metabolic, and neoplastic diseases. The primary therapeutic strategy for osteolytic diseases is to suppress the bone resorption activity of osteoclasts. Dusp1 is a member of the serine/threonine inducible nuclear phosphatase family and has significant anti-inflammatory effects. In this study, Dusp1 overexpression was induced via lentiviral transfection. We found that Dusp1 antagonized RANKL stimulation, mediated the MAPK signaling pathway, and downregulated the key downstream transcription factors c-FOS and NFATc1, thereby reducing the expression of osteoclast-specific genes. Furthermore, Dusp1 reduced the number and activity of osteoclasts both in vivo and in vitro, leading to a diminished bone resorption function. In addition, the results of animal experiments demonstrated that Dusp1 protected mice from LPS-induced skull osteolysis. Overall, our study reveals that Dusp1 suppresses osteoclast formation and activity by downregulating the MAPK/c-FOS/NFATc1 signaling pathway. These findings suggest the potential of Dusp1 to protect against osteolytic diseases. |
| format | Article |
| id | doaj-art-b955c9202b994ded8eaece5fb51cddf8 |
| institution | Kabale University |
| issn | 2045-2322 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj-art-b955c9202b994ded8eaece5fb51cddf82025-08-20T04:01:24ZengNature PortfolioScientific Reports2045-23222025-07-0115111510.1038/s41598-025-05142-6Dusp1 in osteolytic diseases-mechanisms and therapeutic potentialBoyu Liu0Ming Lei1Baicheng Wan2Yanbing Feng3Yilin Teng4Deshuang Xi5Shou Chen6Gaofeng Zeng7Shaohui Zong8Department of Spine Osteopathia, The First Affiliated Hospital of Guangxi Medical University, Guangxi Medical UniversityDepartment of Spine Osteopathia, The First Affiliated Hospital of Guangxi Medical University, Guangxi Medical UniversityDepartment of Spine Osteopathia, The First Affiliated Hospital of Guangxi Medical University, Guangxi Medical UniversityDepartment of Spine Osteopathia, The First Affiliated Hospital of Guangxi Medical University, Guangxi Medical UniversityDepartment of Spine Osteopathia, The First Affiliated Hospital of Guangxi Medical University, Guangxi Medical UniversityDepartment of Spine Osteopathia, The First Affiliated Hospital of Guangxi Medical University, Guangxi Medical UniversityDepartment of Spine Osteopathia, The First Affiliated Hospital of Guangxi Medical University, Guangxi Medical UniversityDepartment of Nutrition and Food Hygiene, College of Public Hygiene of Guangxi Medical UniversityDepartment of Spine Osteopathia, The First Affiliated Hospital of Guangxi Medical University, Guangxi Medical UniversityAbstract Osteolytic diseases are a significant and escalating global public health issue, driven by the acceleration of population aging and the rising incidence of degenerative, metabolic, and neoplastic diseases. The primary therapeutic strategy for osteolytic diseases is to suppress the bone resorption activity of osteoclasts. Dusp1 is a member of the serine/threonine inducible nuclear phosphatase family and has significant anti-inflammatory effects. In this study, Dusp1 overexpression was induced via lentiviral transfection. We found that Dusp1 antagonized RANKL stimulation, mediated the MAPK signaling pathway, and downregulated the key downstream transcription factors c-FOS and NFATc1, thereby reducing the expression of osteoclast-specific genes. Furthermore, Dusp1 reduced the number and activity of osteoclasts both in vivo and in vitro, leading to a diminished bone resorption function. In addition, the results of animal experiments demonstrated that Dusp1 protected mice from LPS-induced skull osteolysis. Overall, our study reveals that Dusp1 suppresses osteoclast formation and activity by downregulating the MAPK/c-FOS/NFATc1 signaling pathway. These findings suggest the potential of Dusp1 to protect against osteolytic diseases.https://doi.org/10.1038/s41598-025-05142-6Dusp1OverexpressionLentivirusOsteoclastOsteolysisMAPK |
| spellingShingle | Boyu Liu Ming Lei Baicheng Wan Yanbing Feng Yilin Teng Deshuang Xi Shou Chen Gaofeng Zeng Shaohui Zong Dusp1 in osteolytic diseases-mechanisms and therapeutic potential Scientific Reports Dusp1 Overexpression Lentivirus Osteoclast Osteolysis MAPK |
| title | Dusp1 in osteolytic diseases-mechanisms and therapeutic potential |
| title_full | Dusp1 in osteolytic diseases-mechanisms and therapeutic potential |
| title_fullStr | Dusp1 in osteolytic diseases-mechanisms and therapeutic potential |
| title_full_unstemmed | Dusp1 in osteolytic diseases-mechanisms and therapeutic potential |
| title_short | Dusp1 in osteolytic diseases-mechanisms and therapeutic potential |
| title_sort | dusp1 in osteolytic diseases mechanisms and therapeutic potential |
| topic | Dusp1 Overexpression Lentivirus Osteoclast Osteolysis MAPK |
| url | https://doi.org/10.1038/s41598-025-05142-6 |
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