Mapk7 enhances osteogenesis and suppresses adipogenesis by activating Lrp6/β-catenin signaling axis in mesenchymal stem cells
Abstract The lineage commitment and differentiation of mesenchymal stem cells (MSCs) play a crucial role in bone homeostasis. MAPK7 (Mitogen-activated protein kinase 7), a member of MAPK family, controls cell differentiation, proliferation and survival. However, the specific role of Mapk7 in regulat...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2025-02-01
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| Series: | Communications Biology |
| Online Access: | https://doi.org/10.1038/s42003-025-07765-x |
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| author | Chuan Li Jiahui Long Shuqing Chen Liru Tian Ya Xiao Shulin Chen Deying Su Baolin Zhang Peiqiang Su Liao Zhiheng Caixia Xu |
| author_facet | Chuan Li Jiahui Long Shuqing Chen Liru Tian Ya Xiao Shulin Chen Deying Su Baolin Zhang Peiqiang Su Liao Zhiheng Caixia Xu |
| author_sort | Chuan Li |
| collection | DOAJ |
| description | Abstract The lineage commitment and differentiation of mesenchymal stem cells (MSCs) play a crucial role in bone homeostasis. MAPK7 (Mitogen-activated protein kinase 7), a member of MAPK family, controls cell differentiation, proliferation and survival. However, the specific role of Mapk7 in regulating osteogenic and adipogenic differentiation of MSCs remains to be determined. In this study, depletion of Mapk7 in MSCs by crossing Prx1-Cre mice to Mapk7 flox/flox resulted in severe low bone mass and accumulation of fat in bone marrow exhibiting osteoporosis (OP) in mice. Mapk7 promoted osteogenic differentiation and inhibited adipogenic differentiation of MSCs after knocking out and over-expressing Mapk7 in vitro. Mechanistically, Mapk7 activated Wnt/β-catenin signaling by phosphorylating Lrp6 at Ser1490, which ultimately enhanced osteogenesis and suppressed adipogenesis of MSCs. This is of great clinical and scientific significance for understanding biological function of Mapk7 and developing potential therapeutic targets for treatment of MSCs differentiation imbalance related bone diseases, such as, osteoporosis. |
| format | Article |
| id | doaj-art-1b8fcf944e3f4850acefae2398d970ec |
| institution | DOAJ |
| issn | 2399-3642 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Communications Biology |
| spelling | doaj-art-1b8fcf944e3f4850acefae2398d970ec2025-08-20T03:03:38ZengNature PortfolioCommunications Biology2399-36422025-02-018111510.1038/s42003-025-07765-xMapk7 enhances osteogenesis and suppresses adipogenesis by activating Lrp6/β-catenin signaling axis in mesenchymal stem cellsChuan Li0Jiahui Long1Shuqing Chen2Liru Tian3Ya Xiao4Shulin Chen5Deying Su6Baolin Zhang7Peiqiang Su8Liao Zhiheng9Caixia Xu10Research Center for Translational Medicine, The First Affiliated Hospital of Sun Yat-sen UniversityResearch Center for Translational Medicine, The First Affiliated Hospital of Sun Yat-sen UniversityDepartment of Traditional Chinese Medicine, The First Affiliated Hospital, Sun Yat-sen UniversityResearch Center for Translational Medicine, The First Affiliated Hospital of Sun Yat-sen UniversityResearch Center for Translational Medicine, The First Affiliated Hospital of Sun Yat-sen UniversityResearch Center for Translational Medicine, The First Affiliated Hospital of Sun Yat-sen UniversityResearch Center for Translational Medicine, The First Affiliated Hospital of Sun Yat-sen UniversityGuangdong Provincial Key Laboratory of Orthopedics and Traumatology, Department of Spine Surgery, The First Affiliated Hospital of Sun Yat-sen UniversityGuangdong Provincial Key Laboratory of Orthopedics and Traumatology, Department of Spine Surgery, The First Affiliated Hospital of Sun Yat-sen UniversityGuangdong Provincial Key Laboratory of Orthopedics and Traumatology, Department of Spine Surgery, The First Affiliated Hospital of Sun Yat-sen UniversityResearch Center for Translational Medicine, The First Affiliated Hospital of Sun Yat-sen UniversityAbstract The lineage commitment and differentiation of mesenchymal stem cells (MSCs) play a crucial role in bone homeostasis. MAPK7 (Mitogen-activated protein kinase 7), a member of MAPK family, controls cell differentiation, proliferation and survival. However, the specific role of Mapk7 in regulating osteogenic and adipogenic differentiation of MSCs remains to be determined. In this study, depletion of Mapk7 in MSCs by crossing Prx1-Cre mice to Mapk7 flox/flox resulted in severe low bone mass and accumulation of fat in bone marrow exhibiting osteoporosis (OP) in mice. Mapk7 promoted osteogenic differentiation and inhibited adipogenic differentiation of MSCs after knocking out and over-expressing Mapk7 in vitro. Mechanistically, Mapk7 activated Wnt/β-catenin signaling by phosphorylating Lrp6 at Ser1490, which ultimately enhanced osteogenesis and suppressed adipogenesis of MSCs. This is of great clinical and scientific significance for understanding biological function of Mapk7 and developing potential therapeutic targets for treatment of MSCs differentiation imbalance related bone diseases, such as, osteoporosis.https://doi.org/10.1038/s42003-025-07765-x |
| spellingShingle | Chuan Li Jiahui Long Shuqing Chen Liru Tian Ya Xiao Shulin Chen Deying Su Baolin Zhang Peiqiang Su Liao Zhiheng Caixia Xu Mapk7 enhances osteogenesis and suppresses adipogenesis by activating Lrp6/β-catenin signaling axis in mesenchymal stem cells Communications Biology |
| title | Mapk7 enhances osteogenesis and suppresses adipogenesis by activating Lrp6/β-catenin signaling axis in mesenchymal stem cells |
| title_full | Mapk7 enhances osteogenesis and suppresses adipogenesis by activating Lrp6/β-catenin signaling axis in mesenchymal stem cells |
| title_fullStr | Mapk7 enhances osteogenesis and suppresses adipogenesis by activating Lrp6/β-catenin signaling axis in mesenchymal stem cells |
| title_full_unstemmed | Mapk7 enhances osteogenesis and suppresses adipogenesis by activating Lrp6/β-catenin signaling axis in mesenchymal stem cells |
| title_short | Mapk7 enhances osteogenesis and suppresses adipogenesis by activating Lrp6/β-catenin signaling axis in mesenchymal stem cells |
| title_sort | mapk7 enhances osteogenesis and suppresses adipogenesis by activating lrp6 β catenin signaling axis in mesenchymal stem cells |
| url | https://doi.org/10.1038/s42003-025-07765-x |
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