| pubmed-article:20814988 | pubmed:abstractText | Evidence demonstrates that sympathetic nervous system (SNS) activation causes osteopenia via ?(2)-adrenoceptor (?2-AR) signaling. Here we show that female mice with chronic sympathetic hyperactivity owing to double knockout of adrenoceptors that negatively regulate norepinephrine release, ?(2A)-AR and ?(2C)-AR (?(2A) /?(2C)-ARKO), present an unexpected and generalized phenotype of high bone mass with decreased bone resorption and increased formation. In ?(2A) /?(2C)-ARKO versus wild-type (WT) mice, micro-computed tomographic (µCT) 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-?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 ?(2)-AR mRNA expression also was similar in KO and WT littermates, whereas ?(2A)-, ?(2B)- and ?(2C)-AR mRNAs were detected in the tibia of WT mice and in osteoblast-like MC3T3-E1 cells. By immunohistochemistry, we detected ?(2A)-, ?(2B)-, ?(2C)- and ?(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 ?(2)-AR agonist clonidine and to the nonspecific ?-AR antagonist phentolamine. These findings suggest that ?(2)-AR is not the single adrenoceptor involved in bone turnover regulation and show that ?(2)-AR signaling also may mediate the SNS actions in the skeleton. | lld:pubmed |
