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dc.contributorSistema FMUSP-HC: Faculdade de Medicina da Universidade de São Paulo (FMUSP) e Hospital das Clínicas da FMUSP
dc.contributor.authorNEOFITI-PAPI, Bianca
dc.contributor.authorALBUQUERQUE, Ruda P.
dc.contributor.authorMIRANDA-RODRIGUES, Manuela
dc.contributor.authorGONCALVES, Natalia J. N.
dc.contributor.authorJORGETTI, Vanda
dc.contributor.authorBRUM, Patricia C.
dc.contributor.authorFERREIRA, Julio C. B.
dc.contributor.authorGOUVEIA, Cecilia H. A.
dc.date.accessioned2019-09-23T14:21:33Z-
dc.date.available2019-09-23T14:21:33Z-
dc.date.issued2019
dc.identifier.citationTHYROID, v.29, n.8, p.1060-1072, 2019
dc.identifier.issn1050-7256
dc.identifier.urihttps://observatorio.fm.usp.br/handle/OPI/33588-
dc.description.abstractBackground: Thyrotoxicosis increases bone turnover, resulting in net bone loss. Sympathetic nervous system (SNS) activation, via beta 2-adrenoceptor (beta 2-AR) signaling, also has osteopenic effects. Because thyroid hormones (TH) interact with the SNS to regulate several physiological processes, we hypothesized that this interaction also occurs to regulate bone mass. Previous studies support this hypothesis, as alpha 2-AR knockout (KO) mice are less susceptible to thyrotoxicosis-induced osteopenia. Here, we evaluated whether TH-SNS interactions in bone involve beta 2-AR signaling. Methods: Thyrotoxicosis was induced in 120-day-old female and male mice with beta 2-AR gene inactivation (beta 2-AR(-/-)) by daily treatment with supraphysiological doses of triiodothyronine (T3) for 12 weeks. The impact of thyrotoxicosis on femoral bone microarchitecture, remodeling, fracture risk, and gene expression of the receptor activator of nuclear factor-kappa-B (RANK)-RANK ligand (RANKL)-osteoprotegerin (OPG) pathway was evaluated. In addition, the effect of the beta 2-AR-specific agonist clenbuterol (CL) on cAMP accumulation was determined in osteoblastic (MC3T3-E1) cells treated with T3 and/or 17 beta-estradiol (E2). Results: Thyrotoxicosis negatively affected trabecular bone microarchitecture in wild-type (WT) females, but this effect was milder or nonexistent in beta 2-AR(-/-) animals, whereas the opposite was seen in males. T3 treatment increased the femoral RANKL/OPG mRNA ratio and the endosteal perimeter and medullary area of the diaphysis in WT females and males, but not in beta 2-AR(-/-) mice, suggesting that T3 promotes endosteal resorption in cortical bone, in a mechanism that involves beta 2-AR signaling. T3 treatment increased endocortical mineral apposition rate only in WT females but not in beta 2-AR(-/-) mice, suggesting that TH also induce bone formation in a beta 2-AR signaling-dependent mechanism. T3 treatment decreased femoral resistance to fracture only in WT females, but not in KO mice. E2 and CL similarly increased cAMP accumulation in MC3T3-E1 cells; whereas T3 alone had no effect, but it completely blocked E2-stimulated cAMP accumulation, suggesting that some T3 effects on bone may involve E2/cAMP signaling in osteoblasts. Conclusions: These findings sustain the hypothesis that T3 interacts with the SNS to regulate bone morphophysiology in a beta 2-AR signaling-dependent mechanism. The data also reveal sex as an important modifier of skeletal manifestations of thyrotoxicosis, as well as a modifier of the TH-SNS interactions to control bone microarchitecture, remodeling, and resistance to fracture.eng
dc.language.isoeng
dc.publisherMARY ANN LIEBERT, INCeng
dc.relation.ispartofThyroid
dc.rightsrestrictedAccesseng
dc.subjectthyroid hormoneseng
dc.subjectsympathetic nervous systemeng
dc.subjectbeta 2-adrenoceptoreng
dc.subjectthyrotoxicosis and boneeng
dc.subject.othersympathetic-nervous-systemeng
dc.subject.otherbone-masseng
dc.subject.otherparathyroid-hormoneeng
dc.subject.otherthyroid-hormoneeng
dc.subject.otherosteoporosiseng
dc.subject.otherhyperthyroidismeng
dc.subject.otherpropranololeng
dc.subject.otherdisruptioneng
dc.subject.otherestrogeneng
dc.subject.otherproteineng
dc.titleThyrotoxicosis Involves beta 2-Adrenoceptor Signaling to Negatively Affect Microarchitecture and Biomechanical Properties of the Femureng
dc.typearticleeng
dc.rights.holderCopyright MARY ANN LIEBERT, INCeng
dc.identifier.doi10.1089/thy.2018.0259
dc.identifier.pmid31264512
dc.subject.wosEndocrinology & Metabolismeng
dc.type.categoryoriginal articleeng
dc.type.versionpublishedVersioneng
hcfmusp.author.externalNEOFITI-PAPI, Bianca:Univ Sao Paulo, Inst Biomed Sci, Dept Anat, Av Prof LineuPrestes 2415, BR-05508000 Sao Paulo, SP, Brazil; Univ Sao Paulo, Sch Med, Sao Paulo, Brazil
hcfmusp.author.externalALBUQUERQUE, Ruda P.:Univ Sao Paulo, Inst Biomed Sci, Dept Anat, Av Prof LineuPrestes 2415, BR-05508000 Sao Paulo, SP, Brazil
hcfmusp.author.externalMIRANDA-RODRIGUES, Manuela:Univ Sao Paulo, Inst Biomed Sci, Dept Anat, Av Prof LineuPrestes 2415, BR-05508000 Sao Paulo, SP, Brazil; Univ Western Ontario, Dept Genet Med, London, ON, Canada
hcfmusp.author.externalGONCALVES, Natalia J. N.:RDO Diagnost Med, Sao Paulo, Brazil
hcfmusp.author.externalBRUM, Patricia C.:Univ Sao Paulo, Sch Phys Educ & Sport, Sao Paulo, Brazil
hcfmusp.author.externalFERREIRA, Julio C. B.:Univ Sao Paulo, Inst Biomed Sci, Dept Anat, Av Prof LineuPrestes 2415, BR-05508000 Sao Paulo, SP, Brazil
hcfmusp.author.externalGOUVEIA, Cecilia H. A.:Univ Sao Paulo, Inst Biomed Sci, Dept Anat, Av Prof LineuPrestes 2415, BR-05508000 Sao Paulo, SP, Brazil; Univ Sao Paulo, Sch Med, Sao Paulo, Brazil
hcfmusp.description.beginpage1060
hcfmusp.description.endpage1072
hcfmusp.description.issue8
hcfmusp.description.volume29
hcfmusp.origemWOS
hcfmusp.origem.idWOS:000481888700005
hcfmusp.origem.id2-s2.0-85071189637
hcfmusp.publisher.cityNEW ROCHELLEeng
hcfmusp.publisher.countryUSAeng
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dc.description.indexMEDLINEeng
dc.identifier.eissn1557-9077
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hcfmusp.scopus.lastupdate2022-05-06-
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