Mice lacking DKK1 in T cells exhibit high bone mass and are protected from estrogen-deficiency-induced bone loss
Summary: The Wnt inhibitor Dickkopf-1 (DKK1) is a negative regulator of bone formation and bone mass and is dysregulated in various bone diseases. How DKK1 contributes to postmenopausal osteoporosis, however, remains poorly understood. Here, we show that mice lacking DKK1 in T cells are protected fr...
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| Format: | Article |
| Language: | English |
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Elsevier
2021-03-01
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| Series: | iScience |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2589004221001929 |
| _version_ | 1818611085605863424 |
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| author | Juliane Lehmann Sylvia Thiele Ulrike Baschant Tilman D. Rachner Christof Niehrs Lorenz C. Hofbauer Martina Rauner |
| author_facet | Juliane Lehmann Sylvia Thiele Ulrike Baschant Tilman D. Rachner Christof Niehrs Lorenz C. Hofbauer Martina Rauner |
| author_sort | Juliane Lehmann |
| collection | DOAJ |
| description | Summary: The Wnt inhibitor Dickkopf-1 (DKK1) is a negative regulator of bone formation and bone mass and is dysregulated in various bone diseases. How DKK1 contributes to postmenopausal osteoporosis, however, remains poorly understood. Here, we show that mice lacking DKK1 in T cells are protected from ovariectomy-induced bone loss. Ovariectomy activated CD4+ and CD8+ T cells and increased their production of DKK1. Co-culture of activated T cells with osteoblasts inhibited Wnt signaling in osteoblasts, leading to impaired differentiation. Importantly, DKK1 expression in T cells also controlled physiological bone remodeling. T-cell-deficient Dkk1 knock-out mice had a higher bone mass with an increased bone formation rate and decreased numbers of osteoclasts compared with controls, a phenotype that was rescued by adoptive transfer of wild-type T cells. Thus, these findings highlight that T cells control bone remodeling in health and disease via their expression of DKK1. |
| first_indexed | 2024-12-16T15:24:43Z |
| format | Article |
| id | doaj.art-b49a9a7229e1475da4e88646176b9934 |
| institution | Directory Open Access Journal |
| issn | 2589-0042 |
| language | English |
| last_indexed | 2024-12-16T15:24:43Z |
| publishDate | 2021-03-01 |
| publisher | Elsevier |
| record_format | Article |
| series | iScience |
| spelling | doaj.art-b49a9a7229e1475da4e88646176b99342022-12-21T22:26:33ZengElsevieriScience2589-00422021-03-01243102224Mice lacking DKK1 in T cells exhibit high bone mass and are protected from estrogen-deficiency-induced bone lossJuliane Lehmann0Sylvia Thiele1Ulrike Baschant2Tilman D. Rachner3Christof Niehrs4Lorenz C. Hofbauer5Martina Rauner6Department of Medicine III, Division of Endocrinology, Diabetes and Bone Diseases, Technische Universität Dresden, Dresden 01307, Germany; Center for Healthy Aging, Technische Universität Dresden, Dresden, GermanyDepartment of Medicine III, Division of Endocrinology, Diabetes and Bone Diseases, Technische Universität Dresden, Dresden 01307, Germany; Center for Healthy Aging, Technische Universität Dresden, Dresden, GermanyDepartment of Medicine III, Division of Endocrinology, Diabetes and Bone Diseases, Technische Universität Dresden, Dresden 01307, Germany; Center for Healthy Aging, Technische Universität Dresden, Dresden, GermanyDepartment of Medicine III, Division of Endocrinology, Diabetes and Bone Diseases, Technische Universität Dresden, Dresden 01307, Germany; Center for Healthy Aging, Technische Universität Dresden, Dresden, GermanyDivision of Molecular Embryology, DKFZ-ZMBH Alliance, Heidelberg, Germany; Institute of Molecular Biology, Mainz, GermanyDepartment of Medicine III, Division of Endocrinology, Diabetes and Bone Diseases, Technische Universität Dresden, Dresden 01307, Germany; Center for Regenerative Therapies Dresden, Technische Universität Dresden, Dresden, GermanyDepartment of Medicine III, Division of Endocrinology, Diabetes and Bone Diseases, Technische Universität Dresden, Dresden 01307, Germany; Center for Healthy Aging, Technische Universität Dresden, Dresden, Germany; Corresponding authorSummary: The Wnt inhibitor Dickkopf-1 (DKK1) is a negative regulator of bone formation and bone mass and is dysregulated in various bone diseases. How DKK1 contributes to postmenopausal osteoporosis, however, remains poorly understood. Here, we show that mice lacking DKK1 in T cells are protected from ovariectomy-induced bone loss. Ovariectomy activated CD4+ and CD8+ T cells and increased their production of DKK1. Co-culture of activated T cells with osteoblasts inhibited Wnt signaling in osteoblasts, leading to impaired differentiation. Importantly, DKK1 expression in T cells also controlled physiological bone remodeling. T-cell-deficient Dkk1 knock-out mice had a higher bone mass with an increased bone formation rate and decreased numbers of osteoclasts compared with controls, a phenotype that was rescued by adoptive transfer of wild-type T cells. Thus, these findings highlight that T cells control bone remodeling in health and disease via their expression of DKK1.http://www.sciencedirect.com/science/article/pii/S2589004221001929Molecular PhysiologyImmunologyCell Biology |
| spellingShingle | Juliane Lehmann Sylvia Thiele Ulrike Baschant Tilman D. Rachner Christof Niehrs Lorenz C. Hofbauer Martina Rauner Mice lacking DKK1 in T cells exhibit high bone mass and are protected from estrogen-deficiency-induced bone loss iScience Molecular Physiology Immunology Cell Biology |
| title | Mice lacking DKK1 in T cells exhibit high bone mass and are protected from estrogen-deficiency-induced bone loss |
| title_full | Mice lacking DKK1 in T cells exhibit high bone mass and are protected from estrogen-deficiency-induced bone loss |
| title_fullStr | Mice lacking DKK1 in T cells exhibit high bone mass and are protected from estrogen-deficiency-induced bone loss |
| title_full_unstemmed | Mice lacking DKK1 in T cells exhibit high bone mass and are protected from estrogen-deficiency-induced bone loss |
| title_short | Mice lacking DKK1 in T cells exhibit high bone mass and are protected from estrogen-deficiency-induced bone loss |
| title_sort | mice lacking dkk1 in t cells exhibit high bone mass and are protected from estrogen deficiency induced bone loss |
| topic | Molecular Physiology Immunology Cell Biology |
| url | http://www.sciencedirect.com/science/article/pii/S2589004221001929 |
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