Global Disruption of α2A Adrenoceptor Barely Affects Bone Tissue but Minimizes the Detrimental Effects of Thyrotoxicosis on Cortical Bone
Evidence shows that sympathetic nervous system (SNS) activation inhibits bone formation and activates bone resorption leading to bone loss. Because thyroid hormone (TH) interacts with the SNS to control several physiological processes, we raised the hypothesis that this interaction also controls bon...
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Frontiers Media S.A.
2018-08-01
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| Series: | Frontiers in Endocrinology |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fendo.2018.00486/full |
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| author | Gisele M. Martins Gisele M. Martins Marília B. C. G. Teixeira Marcos V. Silva Marcos V. Silva Bianca Neofiti-Papi Bianca Neofiti-Papi Manuela Miranda-Rodrigues Manuela Miranda-Rodrigues Patricia C. Brum Cecilia H. A. Gouveia Cecilia H. A. Gouveia |
| author_facet | Gisele M. Martins Gisele M. Martins Marília B. C. G. Teixeira Marcos V. Silva Marcos V. Silva Bianca Neofiti-Papi Bianca Neofiti-Papi Manuela Miranda-Rodrigues Manuela Miranda-Rodrigues Patricia C. Brum Cecilia H. A. Gouveia Cecilia H. A. Gouveia |
| author_sort | Gisele M. Martins |
| collection | DOAJ |
| description | Evidence shows that sympathetic nervous system (SNS) activation inhibits bone formation and activates bone resorption leading to bone loss. Because thyroid hormone (TH) interacts with the SNS to control several physiological processes, we raised the hypothesis that this interaction also controls bone remodeling. We have previously shown that mice with double-gene inactivation of α2A- and -adrenoceptors (α2A/2C-AR−/−) present high bone mass (HBM) phenotype and resistance to thyrotoxicosis-induced osteopenia, which supports a TH-SNS interaction to control bone mass and suggests that it involves α2-AR signaling. Accordingly, we detected expression of α2A-AR, α2B-AR and α2C-AR in the skeleton, and that triiodothyronine (T3) modulates α2C-AR mRNA expression in the bone. Later, we found that mice with single-gene inactivation of α2C-AR (α2C-AR−/−) present low bone mass in the femur and HBM in the vertebra, but that both skeletal sites are resistant to TH-induce osteopenia, showing that the SNS actions occur in a skeletal site-dependent manner, and that thyrotoxicosis depends on α2C-AR signaling to promote bone loss. To further dissect the specific roles of α2-AR subtypes, in this study, we evaluated the skeletal phenotype of mice with single-gene inactivation of α2A-AR (α2A-AR−/−), and the effect of daily treatment with a supraphysiological dose of T3, for 4 or 12 weeks, on bone microarchitecture and bone resistance to fracture. Micro-computed tomographic (μCT) analysis revealed normal trabecular and cortical bone structure in the femur and vertebra of euthyroid α2A-AR−/− mice. Thyrotoxicosis was more detrimental to femoral trabecular bone in α2A-AR−/− than in WT mice, whereas this bone compartment had been previously shown to present resistance to thyrotoxicosis in α2C-AR−/− mice. Altogether these findings reveal that TH excess depends on α2C-AR signaling to negatively affect femoral trabecular bone. In contrast, thyrotoxicosis was more deleterious to femoral and vertebral cortical bone in WT than in α2A-AR−/− mice, suggesting that α2A-AR signaling contributes to TH actions on cortical bone. These findings further support a TH-SNS interaction to control bone physiology, and suggest that α2A-AR and α2C-AR signaling pathways have key roles in the mechanisms through which thyrotoxicosis promotes its detrimental effects on bone remodeling, structure and resistance to fracture. |
| first_indexed | 2024-12-17T06:44:29Z |
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| publishDate | 2018-08-01 |
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| series | Frontiers in Endocrinology |
| spelling | doaj.art-173b222035714d90b5100f0857fe0b932022-12-21T21:59:46ZengFrontiers Media S.A.Frontiers in Endocrinology1664-23922018-08-01910.3389/fendo.2018.00486391129Global Disruption of α2A Adrenoceptor Barely Affects Bone Tissue but Minimizes the Detrimental Effects of Thyrotoxicosis on Cortical BoneGisele M. Martins0Gisele M. Martins1Marília B. C. G. Teixeira2Marcos V. Silva3Marcos V. Silva4Bianca Neofiti-Papi5Bianca Neofiti-Papi6Manuela Miranda-Rodrigues7Manuela Miranda-Rodrigues8Patricia C. Brum9Cecilia H. A. Gouveia10Cecilia H. A. Gouveia11Department of Anatomy, Institute of Biomedical Sciences, University of São Paulo, São Paulo, BrazilDepartment of Morphology, Federal University of Espírito Santo, Vitória, BrazilDepartment of Anatomy, Institute of Biomedical Sciences, University of São Paulo, São Paulo, BrazilDepartment of Anatomy, Institute of Biomedical Sciences, University of São Paulo, São Paulo, BrazilDepartment of Morphology, Federal University of Sergipe, Aracaju, BrazilDepartment of Anatomy, Institute of Biomedical Sciences, University of São Paulo, São Paulo, BrazilSchool of Medicine, University of São Paulo, São Paulo, BrazilDepartment of Anatomy, Institute of Biomedical Sciences, University of São Paulo, São Paulo, BrazilUniversity of Western Ontario, London, ON, CanadaSchool of Physical Education and Sport, University of São Paulo, São Paulo, BrazilDepartment of Anatomy, Institute of Biomedical Sciences, University of São Paulo, São Paulo, BrazilSchool of Medicine, University of São Paulo, São Paulo, BrazilEvidence shows that sympathetic nervous system (SNS) activation inhibits bone formation and activates bone resorption leading to bone loss. Because thyroid hormone (TH) interacts with the SNS to control several physiological processes, we raised the hypothesis that this interaction also controls bone remodeling. We have previously shown that mice with double-gene inactivation of α2A- and -adrenoceptors (α2A/2C-AR−/−) present high bone mass (HBM) phenotype and resistance to thyrotoxicosis-induced osteopenia, which supports a TH-SNS interaction to control bone mass and suggests that it involves α2-AR signaling. Accordingly, we detected expression of α2A-AR, α2B-AR and α2C-AR in the skeleton, and that triiodothyronine (T3) modulates α2C-AR mRNA expression in the bone. Later, we found that mice with single-gene inactivation of α2C-AR (α2C-AR−/−) present low bone mass in the femur and HBM in the vertebra, but that both skeletal sites are resistant to TH-induce osteopenia, showing that the SNS actions occur in a skeletal site-dependent manner, and that thyrotoxicosis depends on α2C-AR signaling to promote bone loss. To further dissect the specific roles of α2-AR subtypes, in this study, we evaluated the skeletal phenotype of mice with single-gene inactivation of α2A-AR (α2A-AR−/−), and the effect of daily treatment with a supraphysiological dose of T3, for 4 or 12 weeks, on bone microarchitecture and bone resistance to fracture. Micro-computed tomographic (μCT) analysis revealed normal trabecular and cortical bone structure in the femur and vertebra of euthyroid α2A-AR−/− mice. Thyrotoxicosis was more detrimental to femoral trabecular bone in α2A-AR−/− than in WT mice, whereas this bone compartment had been previously shown to present resistance to thyrotoxicosis in α2C-AR−/− mice. Altogether these findings reveal that TH excess depends on α2C-AR signaling to negatively affect femoral trabecular bone. In contrast, thyrotoxicosis was more deleterious to femoral and vertebral cortical bone in WT than in α2A-AR−/− mice, suggesting that α2A-AR signaling contributes to TH actions on cortical bone. These findings further support a TH-SNS interaction to control bone physiology, and suggest that α2A-AR and α2C-AR signaling pathways have key roles in the mechanisms through which thyrotoxicosis promotes its detrimental effects on bone remodeling, structure and resistance to fracture.https://www.frontiersin.org/article/10.3389/fendo.2018.00486/fullthyroid hormonethyrotoxicosissympathetic nervous systemα2A-adrenoceptorcortical bonetrabecular bone |
| spellingShingle | Gisele M. Martins Gisele M. Martins Marília B. C. G. Teixeira Marcos V. Silva Marcos V. Silva Bianca Neofiti-Papi Bianca Neofiti-Papi Manuela Miranda-Rodrigues Manuela Miranda-Rodrigues Patricia C. Brum Cecilia H. A. Gouveia Cecilia H. A. Gouveia Global Disruption of α2A Adrenoceptor Barely Affects Bone Tissue but Minimizes the Detrimental Effects of Thyrotoxicosis on Cortical Bone Frontiers in Endocrinology thyroid hormone thyrotoxicosis sympathetic nervous system α2A-adrenoceptor cortical bone trabecular bone |
| title | Global Disruption of α2A Adrenoceptor Barely Affects Bone Tissue but Minimizes the Detrimental Effects of Thyrotoxicosis on Cortical Bone |
| title_full | Global Disruption of α2A Adrenoceptor Barely Affects Bone Tissue but Minimizes the Detrimental Effects of Thyrotoxicosis on Cortical Bone |
| title_fullStr | Global Disruption of α2A Adrenoceptor Barely Affects Bone Tissue but Minimizes the Detrimental Effects of Thyrotoxicosis on Cortical Bone |
| title_full_unstemmed | Global Disruption of α2A Adrenoceptor Barely Affects Bone Tissue but Minimizes the Detrimental Effects of Thyrotoxicosis on Cortical Bone |
| title_short | Global Disruption of α2A Adrenoceptor Barely Affects Bone Tissue but Minimizes the Detrimental Effects of Thyrotoxicosis on Cortical Bone |
| title_sort | global disruption of α2a adrenoceptor barely affects bone tissue but minimizes the detrimental effects of thyrotoxicosis on cortical bone |
| topic | thyroid hormone thyrotoxicosis sympathetic nervous system α2A-adrenoceptor cortical bone trabecular bone |
| url | https://www.frontiersin.org/article/10.3389/fendo.2018.00486/full |
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