dc.creator | Fonseca, Tatiana L. | |
dc.creator | Jorgetti, Vanda | |
dc.creator | Costa, Cristiane C. | |
dc.creator | Capelo, Luciane P. | |
dc.creator | Covarrubias, Ambart E. | |
dc.creator | Moulatlet, Ana C. | |
dc.creator | Teixeira, Marilia B. | |
dc.creator | Hesse, Eric | |
dc.creator | Morethson, Priscilla | |
dc.creator | Beber, Eduardo H. | |
dc.creator | Freitas, Fatima R. | |
dc.creator | Wang, Charles C. | |
dc.creator | Nonaka, Keico O. | |
dc.creator | Oliveira, Ricardo | |
dc.creator | Casarini, Dulce E. | |
dc.creator | Zorn, Telma M. | |
dc.creator | Brum, Patricia C. | |
dc.creator | Gouveia, Cecilia H. | |
dc.date.accessioned | 2012-10-18T23:11:06Z | |
dc.date.accessioned | 2018-07-04T14:45:50Z | |
dc.date.available | 2012-10-18T23:11:06Z | |
dc.date.available | 2018-07-04T14:45:50Z | |
dc.date.created | 2012-10-18T23:11:06Z | |
dc.date.issued | 2011 | |
dc.identifier | JOURNAL OF BONE AND MINERAL RESEARCH, v.26, n.3, p.591-603, 2011 | |
dc.identifier | 0884-0431 | |
dc.identifier | http://producao.usp.br/handle/BDPI/17308 | |
dc.identifier | 10.1002/jbmr.243 | |
dc.identifier | http://dx.doi.org/10.1002/jbmr.243 | |
dc.identifier.uri | http://repositorioslatinoamericanos.uchile.cl/handle/2250/1614113 | |
dc.description.abstract | Evidence demonstrates that sympathetic nervous system (SNS) activation causes osteopenia via beta(2)-adrenoceptor (beta(2)-AR) signaling. Here we show that female mice with chronic sympathetic hyperactivity owing to double knockout of adrenoceptors that negatively regulate norepinephrine release, alpha(2A)-AR and alpha(2C)-AR(alpha(2A)/alpha(2C)-ARKO), present an unexpected and generalized phenotype of high bone mass with decreased bone resorption and increased formation. In alpha(2A)/alpha(2C)-ARKO versus wild-type (WT) mice, micro-computed tomographic (mu CT) analysis showed increased, better connected, and more plate-shaped trabeculae in the femur and vertebra and increased cortical thickness in the vertebra, whereas biomechanical analysis showed increased tibial and femoral strength. Tibial mRNA expression of tartrate-resistant acid phosphatase (TRACP) and receptor activator of NF-kappa B (RANK), which are osteoclast-related factors, was lower in knockout (KO) mice. Plasma leptin and brain mRNA levels of cocaine amphetamine-regulated transcript (CART), which are factors that centrally affect bone turnover, and serum levels of estradiol were similar between mice strains. Tibial beta(2)-AR mRNA expression also was similar in KO and WT littermates, whereas alpha(2A)-, alpha(2B)- and alpha(2C)-AR mRNAs were detected in the tibia of WT mice and in osteoblast-like MC3T3-E1 cells. By immunohistochemistry, we detected alpha(2A)-, alpha(2B)-, alpha(2C)- and beta(2)-ARs in osteoblasts, osteoclasts, and chondrocytes of 18.5-day-old mouse fetuses and 35-day-old mice. Finally, we showed that isolated osteoclasts in culture are responsive to the selective alpha(2)-AR agonist clonidine and to the nonspecific alpha-AR antagonist phentolamine. These findings suggest that beta(2)-AR is not the single adrenoceptor involved in bone turnover regulation and show that alpha(2)-AR signaling also may mediate the SNS actions in the skeleton. (c) 2011 American Society for Bone and Mineral Research. | |
dc.language | eng | |
dc.publisher | WILEY-BLACKWELL | |
dc.relation | Journal of Bone and Mineral Research | |
dc.rights | Copyright WILEY-BLACKWELL | |
dc.rights | restrictedAccess | |
dc.subject | SYMPATHETIC HYPERACTIVITY | |
dc.subject | BONE METABOLISM | |
dc.subject | BONE MASS | |
dc.subject | SNS | |
dc.subject | ADRENERGIC RECEPTORS | |
dc.title | Double disruption of alpha(2A)- and alpha(2C)-adrenoceptors results in sympathetic hyperactivity and high-bone-mass phenotype | |
dc.type | Artículos de revistas | |