Reversal of the diabetic bone signature with anabolic therapies in mice
Abstract The mechanisms underlying the bone disease induced by diabetes are complex and not fully understood; and antiresorptive agents, the current standard of care, do not restore the weakened bone architecture. Herein, we reveal the diabetic bone signature in mice at the tissue, cell, and transcr...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Nature Publishing Group
2023-04-01
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| Series: | Bone Research |
| Online Access: | https://doi.org/10.1038/s41413-023-00261-0 |
| _version_ | 1797801545552625664 |
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| author | Silvia Marino Nisreen Akel Shenyang Li Meloney Cregor Meghan Jones Betiana Perez Gaston Troncoso Jomeeka Meeks Scott Stewart Amy Y. Sato Intawat Nookaew Teresita Bellido |
| author_facet | Silvia Marino Nisreen Akel Shenyang Li Meloney Cregor Meghan Jones Betiana Perez Gaston Troncoso Jomeeka Meeks Scott Stewart Amy Y. Sato Intawat Nookaew Teresita Bellido |
| author_sort | Silvia Marino |
| collection | DOAJ |
| description | Abstract The mechanisms underlying the bone disease induced by diabetes are complex and not fully understood; and antiresorptive agents, the current standard of care, do not restore the weakened bone architecture. Herein, we reveal the diabetic bone signature in mice at the tissue, cell, and transcriptome levels and demonstrate that three FDA-approved bone-anabolic agents correct it. Diabetes decreased bone mineral density (BMD) and bone formation, damaged microarchitecture, increased porosity of cortical bone, and compromised bone strength. Teriparatide (PTH), abaloparatide (ABL), and romosozumab/anti-sclerostin antibody (Scl-Ab) all restored BMD and corrected the deteriorated bone architecture. Mechanistically, PTH and more potently ABL induced similar responses at the tissue and gene signature levels, increasing both formation and resorption with positive balance towards bone gain. In contrast, Scl-Ab increased formation but decreased resorption. All agents restored bone architecture, corrected cortical porosity, and improved mechanical properties of diabetic bone; and ABL and Scl-Ab increased toughness, a fracture resistance index. Remarkably, all agents increased bone strength over the healthy controls even in the presence of severe hyperglycemia. These findings demonstrate the therapeutic value of bone anabolic agents to treat diabetes-induced bone disease and suggest the need for revisiting the approaches for the treatment of bone fragility in diabetes. |
| first_indexed | 2024-03-13T04:52:06Z |
| format | Article |
| id | doaj.art-f8602743f42c4095b8142500de95df68 |
| institution | Directory Open Access Journal |
| issn | 2095-6231 |
| language | English |
| last_indexed | 2024-03-13T04:52:06Z |
| publishDate | 2023-04-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | Bone Research |
| spelling | doaj.art-f8602743f42c4095b8142500de95df682023-06-18T11:09:03ZengNature Publishing GroupBone Research2095-62312023-04-0111111210.1038/s41413-023-00261-0Reversal of the diabetic bone signature with anabolic therapies in miceSilvia Marino0Nisreen Akel1Shenyang Li2Meloney Cregor3Meghan Jones4Betiana Perez5Gaston Troncoso6Jomeeka Meeks7Scott Stewart8Amy Y. Sato9Intawat Nookaew10Teresita Bellido11Department of Physiology and Cell Biology, University of Arkansas for Medical SciencesDepartment of Physiology and Cell Biology, University of Arkansas for Medical SciencesCentral Arkansas Veterans Healthcare System, John L. McClellan Little RockDepartment of Physiology and Cell Biology, University of Arkansas for Medical SciencesDepartment of Physiology and Cell Biology, University of Arkansas for Medical SciencesDepartment of Physiology and Cell Biology, University of Arkansas for Medical SciencesDepartment of Physiology and Cell Biology, University of Arkansas for Medical SciencesDepartment of Physiology and Cell Biology, University of Arkansas for Medical SciencesDepartment of Biostatistics, University of Arkansas for Medical SciencesDepartment of Physiology and Cell Biology, University of Arkansas for Medical SciencesDepartment of Biomedical Informatics, University of Arkansas for Medical SciencesDepartment of Physiology and Cell Biology, University of Arkansas for Medical SciencesAbstract The mechanisms underlying the bone disease induced by diabetes are complex and not fully understood; and antiresorptive agents, the current standard of care, do not restore the weakened bone architecture. Herein, we reveal the diabetic bone signature in mice at the tissue, cell, and transcriptome levels and demonstrate that three FDA-approved bone-anabolic agents correct it. Diabetes decreased bone mineral density (BMD) and bone formation, damaged microarchitecture, increased porosity of cortical bone, and compromised bone strength. Teriparatide (PTH), abaloparatide (ABL), and romosozumab/anti-sclerostin antibody (Scl-Ab) all restored BMD and corrected the deteriorated bone architecture. Mechanistically, PTH and more potently ABL induced similar responses at the tissue and gene signature levels, increasing both formation and resorption with positive balance towards bone gain. In contrast, Scl-Ab increased formation but decreased resorption. All agents restored bone architecture, corrected cortical porosity, and improved mechanical properties of diabetic bone; and ABL and Scl-Ab increased toughness, a fracture resistance index. Remarkably, all agents increased bone strength over the healthy controls even in the presence of severe hyperglycemia. These findings demonstrate the therapeutic value of bone anabolic agents to treat diabetes-induced bone disease and suggest the need for revisiting the approaches for the treatment of bone fragility in diabetes.https://doi.org/10.1038/s41413-023-00261-0 |
| spellingShingle | Silvia Marino Nisreen Akel Shenyang Li Meloney Cregor Meghan Jones Betiana Perez Gaston Troncoso Jomeeka Meeks Scott Stewart Amy Y. Sato Intawat Nookaew Teresita Bellido Reversal of the diabetic bone signature with anabolic therapies in mice Bone Research |
| title | Reversal of the diabetic bone signature with anabolic therapies in mice |
| title_full | Reversal of the diabetic bone signature with anabolic therapies in mice |
| title_fullStr | Reversal of the diabetic bone signature with anabolic therapies in mice |
| title_full_unstemmed | Reversal of the diabetic bone signature with anabolic therapies in mice |
| title_short | Reversal of the diabetic bone signature with anabolic therapies in mice |
| title_sort | reversal of the diabetic bone signature with anabolic therapies in mice |
| url | https://doi.org/10.1038/s41413-023-00261-0 |
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