Advanced search
Start date
Betweenand
(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

Double Disruption of alpha(2A)- and alpha(2C)-Adrenoceptors Results in Sympathetic Hyperactivity and High-Bone-Mass Phenotype

Full text
Author(s):
Show less -
Fonseca, Tatiana L. [1] ; Jorgetti, Vanda [2] ; Costa, Cristiane C. [1] ; Capelo, Luciane P. [1] ; Covarrubias, Ambart E. [3] ; Moulatlet, Ana C. [1] ; Teixeira, Marilia B. [1] ; Hesse, Eric [4] ; Morethson, Priscilla [5] ; Beber, Eduardo H. [1] ; Freitas, Fatima R. [1] ; Wang, Charles C. [6] ; Nonaka, Keico O. [6] ; Oliveira, Ricardo [7] ; Casarini, Dulce E. [8] ; Zorn, Telma M. [3] ; Brum, Patricia C. [9] ; Gouveia, Cecilia H. [1]
Total Authors: 18
Affiliation:
[1] Univ Sao Paulo, Inst Biomed Sci, Dept Anat, BR-05508000 Sao Paulo - Brazil
[2] Univ Sao Paulo, Sch Med, BR-05508000 Sao Paulo - Brazil
[3] Univ Sao Paulo, Inst Biomed Sci, Dept Cell & Dev Biol, BR-05508000 Sao Paulo - Brazil
[4] Hannover Med Sch, Dept Trauma Surg, D-3000 Hannover - Germany
[5] Univ Sao Paulo, Inst Biomed Sci, Dept Physiol & Biophys, BR-05508000 Sao Paulo - Brazil
[6] Univ Fed Sao Carlos, Dept Physiol Sci, BR-13560 Sao Carlos, SP - Brazil
[7] RDO Diagnost Med, Sao Paulo - Brazil
[8] Univ Fed Sao Paulo, Div Renal, Sch Med, Dept Internal Med, Sao Paulo - Brazil
[9] Univ Sao Paulo, Sch Phys Educ & Sport, BR-05508000 Sao Paulo - Brazil
Total Affiliations: 9
Document type: Journal article
Source: Journal of Bone and Mineral Research; v. 26, n. 3, p. 591-603, MAR 2011.
Web of Science Citations: 34
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. (AU)