{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T22:46:29Z","timestamp":1790549189937,"version":"4.1.0"},"reference-count":53,"publisher":"SAGE Publications","issue":"8","license":[{"start":{"date-parts":[[2019,8,1]],"date-time":"2019-08-01T00:00:00Z","timestamp":1564617600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Thyroid\u00ae"],"published-print":{"date-parts":[[2019,8]]},"abstract":"<jats:sec>\n                    <jats:title>Background:<\/jats:title>\n                    <jats:p>\n                      Thyrotoxicosis increases bone turnover, resulting in net bone loss. Sympathetic nervous system (SNS) activation, via \u03b22-adrenoceptor (\u03b22-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\n                      <jats:italic toggle=\"yes\">\u03b12-AR<\/jats:italic>\n                      knockout (KO) mice are less susceptible to thyrotoxicosis-induced osteopenia. Here, we evaluated whether TH-SNS interactions in bone involve \u03b22-AR signaling.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>\n                      Thyrotoxicosis was induced in 120-day-old female and male mice with \u03b22-AR gene inactivation (\n                      <jats:italic toggle=\"yes\">\n                        \u03b22-AR\n                        <jats:sup>\u2212\/\u2212<\/jats:sup>\n                      <\/jats:italic>\n                      ) 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 \u03b22-AR-specific agonist clenbuterol (CL) on cAMP accumulation was determined in osteoblastic (MC3T3-E1) cells treated with T3 and\/or 17\u03b2-estradiol (E2).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>\n                      Thyrotoxicosis negatively affected trabecular bone microarchitecture in wild-type (WT) females, but this effect was milder or nonexistent in\n                      <jats:italic toggle=\"yes\">\n                        \u03b22-AR\n                        <jats:sup>\u2212\/\u2212<\/jats:sup>\n                      <\/jats:italic>\n                      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\n                      <jats:italic toggle=\"yes\">\n                        \u03b22-AR\n                        <jats:sup>\u2212\/\u2212<\/jats:sup>\n                      <\/jats:italic>\n                      mice, suggesting that T3 promotes endosteal resorption in cortical bone, in a mechanism that involves \u03b22-AR signaling. T3 treatment increased endocortical mineral apposition rate only in WT females but not in \u03b22-AR\n                      <jats:sup>\n                        <jats:italic toggle=\"yes\">\u2212\/\u2212<\/jats:italic>\n                      <\/jats:sup>\n                      mice, suggesting that TH also induce bone formation in a \u03b22-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.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions:<\/jats:title>\n                    <jats:p>These findings sustain the hypothesis that T3 interacts with the SNS to regulate bone morphophysiology in a \u03b22-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.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1089\/thy.2018.0259","type":"journal-article","created":{"date-parts":[[2019,7,2]],"date-time":"2019-07-02T07:13:43Z","timestamp":1562051623000},"page":"1060-1072","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":7,"title":["Thyrotoxicosis Involves \u03b22-Adrenoceptor Signaling to Negatively Affect Microarchitecture and Biomechanical Properties of the Femur"],"prefix":"10.1177","volume":"29","author":[{"given":"Bianca","family":"Neofiti-Papi","sequence":"first","affiliation":[{"name":"Department of Anatomy, Institute of Biomedical Sciences, University of S\u00e3o Paulo, S\u00e3o Paulo, Brazil."},{"name":"School of Medicine, and University of S\u00e3o Paulo, S\u00e3o Paulo, Brazil."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruda P.","family":"Albuquerque","sequence":"additional","affiliation":[{"name":"Department of Anatomy, Institute of Biomedical Sciences, University of S\u00e3o Paulo, S\u00e3o Paulo, Brazil."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manuela","family":"Miranda-Rodrigues","sequence":"additional","affiliation":[{"name":"Department of Anatomy, Institute of Biomedical Sciences, University of S\u00e3o Paulo, S\u00e3o Paulo, Brazil."},{"name":"Department of Genetic Medicine, University of Western Ontario, London, Ontario, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natalia J.N.","family":"Gon\u00e7alves","sequence":"additional","affiliation":[{"name":"RDO Diagn\u00f3sticos M\u00e9dicos, S\u00e3o Paulo, Brazil."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vanda","family":"Jorgetti","sequence":"additional","affiliation":[{"name":"School of Medicine, and University of S\u00e3o Paulo, S\u00e3o Paulo, Brazil."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patricia C.","family":"Brum","sequence":"additional","affiliation":[{"name":"School of Physical Education and Sport, University of S\u00e3o Paulo, S\u00e3o Paulo, Brazil."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julio C.B.","family":"Ferreira","sequence":"additional","affiliation":[{"name":"Department of Anatomy, Institute of Biomedical Sciences, University of S\u00e3o Paulo, S\u00e3o Paulo, Brazil."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cecilia H.A.","family":"Gouveia","sequence":"additional","affiliation":[{"name":"Department of Anatomy, Institute of Biomedical Sciences, University of S\u00e3o Paulo, S\u00e3o Paulo, Brazil."},{"name":"School of 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