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

Autor(es):Mostrar menos -

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]

Afiliação do(s) autor(es)

^[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

• Tipo de documento: Artigo Científico
• Fonte: Journal of Bone and Mineral Research; v. 26, n. 3, p. 591-603, MAR 2011.
• Citações Web of Science: 33

Resumo

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)

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