Regulation of sclerostin in glucocorticoid-induced osteoporosis (GIO) in mice and humans
Glucocorticoids (GC) are used for the treatment of inflammatory diseases, including various forms of arthritis. However, their use is limited, amongst others, by adverse effects on bone. The Wnt and bone formation inhibitor sclerostin was recently implicated in the pathogenesis of GC-induced osteopo...
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| Format: | Article |
| Language: | English |
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Bioscientifica
2019-07-01
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| Series: | Endocrine Connections |
| Subjects: | |
| Online Access: | https://ec.bioscientifica.com/view/journals/ec/8/7/EC-19-0104.xml |
| _version_ | 1818340439843930112 |
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| author | Sylvia Thiele Anke Hannemann Maria Winzer Ulrike Baschant Heike Weidner Matthias Nauck Rajesh V Thakker Martin Bornhäuser Lorenz C Hofbauer Martina Rauner |
| author_facet | Sylvia Thiele Anke Hannemann Maria Winzer Ulrike Baschant Heike Weidner Matthias Nauck Rajesh V Thakker Martin Bornhäuser Lorenz C Hofbauer Martina Rauner |
| author_sort | Sylvia Thiele |
| collection | DOAJ |
| description | Glucocorticoids (GC) are used for the treatment of inflammatory diseases, including various forms of arthritis. However, their use is limited, amongst others, by adverse effects on bone. The Wnt and bone formation inhibitor sclerostin was recently implicated in the pathogenesis of GC-induced osteoporosis. However, data are ambiguous. The aim of this study was to assess the regulation of sclerostin by GC using several mouse models with high GC levels and two independent cohorts of patients treated with GC. Male 24-week-old C57BL/6 and 18-week-old DBA/1 mice exposed to GC and 12-week-old mice with endogenous hypercortisolism displayed reduced bone formation as indicated by reduced levels of P1NP and increased serum sclerostin levels. The expression of sclerostin in femoral bone tissue and GC-treated bone marrow stromal cells, however, was not consistently altered. In contrast, GC dose- and time-dependently suppressed sclerostin at mRNA and protein levels in human mesenchymal stromal cells, and this effect was GC receptor dependent. In line with the human cell culture data, patients with rheumatoid arthritis (RA, n = 101) and polymyalgia rheumatica (PMR, n = 21) who were exposed to GC had lower serum levels of sclerostin than healthy age- and s ex-matched controls (−40%, P < 0.01 and −26.5%, P < 0.001, respectively). In summary, sclerostin appears to be differentially regulated by GC in mice and humans as it is suppressed by GCs in humans but is not consistently altered in mice. Further studies are required to delineate the differences between GC regulation of sclerostin in mice and humans and assess whether sclerostin mediates GC-induced osteoporosis in humans. |
| first_indexed | 2024-12-13T15:42:55Z |
| format | Article |
| id | doaj.art-859dcd8053174ff2af1c895a18d3602b |
| institution | Directory Open Access Journal |
| issn | 2049-3614 2049-3614 |
| language | English |
| last_indexed | 2024-12-13T15:42:55Z |
| publishDate | 2019-07-01 |
| publisher | Bioscientifica |
| record_format | Article |
| series | Endocrine Connections |
| spelling | doaj.art-859dcd8053174ff2af1c895a18d3602b2022-12-21T23:39:46ZengBioscientificaEndocrine Connections2049-36142049-36142019-07-0187923934https://doi.org/10.1530/EC-19-0104Regulation of sclerostin in glucocorticoid-induced osteoporosis (GIO) in mice and humansSylvia Thiele0Anke Hannemann1Maria Winzer2Ulrike Baschant3Heike Weidner4Matthias Nauck5Rajesh V Thakker6Martin Bornhäuser7Lorenz C Hofbauer8Martina Rauner9DFG Research Center and Cluster of Excellence for Regenerative Therapies, Technical University, Dresden, GermanyInstitute of Clinical Chemistry and Laboratory Medicine, University Medicine Greifswald, Greifswald, GermanyDepartment of Medicine III, Technische Universität Dresden, Dresden, Germany; Center for Healthy Aging, Technische Universität Dresden, Dresden, GermanyDepartment of Medicine III, Technische Universität Dresden, Dresden, Germany; Center for Healthy Aging, Technische Universität Dresden, Dresden, GermanyDepartment of Medicine III, Technische Universität Dresden, Dresden, Germany; Center for Healthy Aging, Technische Universität Dresden, Dresden, GermanyInstitute of Clinical Chemistry and Laboratory Medicine, University Medicine Greifswald, Greifswald, GermanyAcademic Endocrine Unit, Radcliffe Department of Medicine University of Oxford, Oxford Centre for Diabetes, Endocrinology, and Metabolism, Churchill Hospital, Oxford, UKDepartment of Medicine I, Technische Universität Dresden, Dresden, Germany; DFG Research Center and Cluster of Excellence for Regenerative Therapies, Technical University, Dresden, GermanyDFG Research Center and Cluster of Excellence for Regenerative Therapies, Technical University, Dresden, Germany; DFG Research Center and Cluster of Excellence for Regenerative Therapies, Technical University, Dresden, GermanyDepartment of Medicine III, Technische Universität Dresden, Dresden, Germany; Center for Healthy Aging, Technische Universität Dresden, Dresden, GermanyGlucocorticoids (GC) are used for the treatment of inflammatory diseases, including various forms of arthritis. However, their use is limited, amongst others, by adverse effects on bone. The Wnt and bone formation inhibitor sclerostin was recently implicated in the pathogenesis of GC-induced osteoporosis. However, data are ambiguous. The aim of this study was to assess the regulation of sclerostin by GC using several mouse models with high GC levels and two independent cohorts of patients treated with GC. Male 24-week-old C57BL/6 and 18-week-old DBA/1 mice exposed to GC and 12-week-old mice with endogenous hypercortisolism displayed reduced bone formation as indicated by reduced levels of P1NP and increased serum sclerostin levels. The expression of sclerostin in femoral bone tissue and GC-treated bone marrow stromal cells, however, was not consistently altered. In contrast, GC dose- and time-dependently suppressed sclerostin at mRNA and protein levels in human mesenchymal stromal cells, and this effect was GC receptor dependent. In line with the human cell culture data, patients with rheumatoid arthritis (RA, n = 101) and polymyalgia rheumatica (PMR, n = 21) who were exposed to GC had lower serum levels of sclerostin than healthy age- and s ex-matched controls (−40%, P < 0.01 and −26.5%, P < 0.001, respectively). In summary, sclerostin appears to be differentially regulated by GC in mice and humans as it is suppressed by GCs in humans but is not consistently altered in mice. Further studies are required to delineate the differences between GC regulation of sclerostin in mice and humans and assess whether sclerostin mediates GC-induced osteoporosis in humans.https://ec.bioscientifica.com/view/journals/ec/8/7/EC-19-0104.xmlsclerostinglucocorticoid-induced osteoporosisbone remodelingbone marrow stromal cellsglucocorticoid receptor |
| spellingShingle | Sylvia Thiele Anke Hannemann Maria Winzer Ulrike Baschant Heike Weidner Matthias Nauck Rajesh V Thakker Martin Bornhäuser Lorenz C Hofbauer Martina Rauner Regulation of sclerostin in glucocorticoid-induced osteoporosis (GIO) in mice and humans Endocrine Connections sclerostin glucocorticoid-induced osteoporosis bone remodeling bone marrow stromal cells glucocorticoid receptor |
| title | Regulation of sclerostin in glucocorticoid-induced osteoporosis (GIO) in mice and humans |
| title_full | Regulation of sclerostin in glucocorticoid-induced osteoporosis (GIO) in mice and humans |
| title_fullStr | Regulation of sclerostin in glucocorticoid-induced osteoporosis (GIO) in mice and humans |
| title_full_unstemmed | Regulation of sclerostin in glucocorticoid-induced osteoporosis (GIO) in mice and humans |
| title_short | Regulation of sclerostin in glucocorticoid-induced osteoporosis (GIO) in mice and humans |
| title_sort | regulation of sclerostin in glucocorticoid induced osteoporosis gio in mice and humans |
| topic | sclerostin glucocorticoid-induced osteoporosis bone remodeling bone marrow stromal cells glucocorticoid receptor |
| url | https://ec.bioscientifica.com/view/journals/ec/8/7/EC-19-0104.xml |
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