The role of the sympathetic nervous system in controlling bone metabolism

Togari, Akifumi; Arai, M.; Kondo, Ayami

doi:10.1517/14728222.9.5.931

Cited by 75 publications

(42 citation statements)

References 71 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Consistent with the BMD findings, the mCT analysis (Fig. 2B) showed increased BV/TV in L 4 and in the distal femurs of KO animals (80% and 57%, respectively). An increase in Tb.N also was observed in L 4 of KO mice (35%).…”

Section: Resultssupporting

confidence: 86%

Double disruption of α2A- and α2C -adrenoceptors results in sympathetic hyperactivity and high-bone-mass phenotype

Fonseca

Jorgetti

Costa

et al. 2010

Journal of Bone and Mineral Research

View full text Add to dashboard Cite

Evidence demonstrates that sympathetic nervous system (SNS) activation causes osteopenia via b 2 -adrenoceptor (b2-AR) signaling. Here we show that female mice with chronic sympathetic hyperactivity owing to double knockout of adrenoceptors that negatively regulate norepinephrine release, a 2A -AR and a 2C -AR (a 2A /a 2C -ARKO), present an unexpected and generalized phenotype of high bone mass with decreased bone resorption and increased formation. In a 2A /a 2C -ARKO versus wild-type (WT) mice, micro-computed tomographic (mCT) 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-kB (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 b 2 -AR mRNA expression also was similar in KO and WT littermates, whereas a 2A -, a 2B -and a 2C -AR mRNAs were detected in the tibia of WT mice and in osteoblast-like MC3T3-E1 cells. By immunohistochemistry, we detected a 2A -, a 2B -, a 2C -and b 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 a 2 -AR agonist clonidine and to the nonspecific a-AR antagonist phentolamine. These findings suggest that b 2 -AR is not the single adrenoceptor involved in bone turnover regulation and show that a 2 -AR signaling also may mediate the SNS actions in the skeleton. ß

show abstract

Section: Resultssupporting

confidence: 86%

Double disruption of α2A- and α2C -adrenoceptors results in sympathetic hyperactivity and high-bone-mass phenotype

Fonseca

Jorgetti

Costa

et al. 2010

Journal of Bone and Mineral Research

View full text Add to dashboard Cite

show abstract

“…Similar observations were described for keratinocytes (Pullar et al, 2006) and airway smooth muscle cells (Hirshman et al, 2001;Hirshman et al, 2005). Although it is well known that osteoblasts express badrenergic receptors ) and that the nervous system is involved in the regulation of bone turnover (Togari et al, 2005), the activation of b-adrenoreceptors in osteoblasts has not been previously linked to alteration of the actin cytoskeleton.…”

Section: Discussionsupporting

confidence: 74%

Impact of substrate elasticity on human hematopoietic stem and progenitor cell adhesion and motility

Lee-Thedieck

Rauch

Fiammengo

et al. 2012

Journal of Cell Science

View full text Add to dashboard Cite

SummaryIn the bone marrow, hematopoietic stem cells (HSCs) reside in endosteal and vascular niches. The interactions with the niches are essential for the maintenance of HSC number and properties. Although the molecular nature of these interactions is well understood, little is known about the role of physical parameters such as matrix elasticity. Osteoblasts, the major cellular component of the endosteal HSC niche, flatten during HSC mobilization. We show that this process is accompanied by osteoblast stiffening, demonstrating that not only biochemical signals but also mechanical properties of the niche are modulated. HSCs react to stiffer substrates with increased cell adhesion and migration, which could facilitate the exit of HSCs from the niche. These results indicate that matrix elasticity is an important factor in regulating the retention of HSCs in the endosteal niche and should be considered in attempts to propagate HSCs in vitro for clinical applications.

show abstract

“…The proliferation and differentiation of mononuclear preosteoclasts and the activity of the differentiated osteoclasts are controlled by numerous systemic hormones, cytokines, growth factors, and the nervous system. Recently, the sympathetic nervous system has been implicated in bone metabolism (3,6,7,19). We previously reported that the α 1B -, α 2B -, and β 2-ARs; substance P receptor (SP-R); vasoactive intestinal peptide receptor (VIP-R); and calcitonin gene-related peptide receptor (CGRP-R) are expressed in human osteoclastic cells and that a β -adrenergic agonist was able to directly stimulate bone-resorbing activity in human osteoclastlike cells (3,20).…”

Section: Introductionmentioning

confidence: 99%

Demonstration of Direct Neurite–Osteoclastic Cell Communication In Vitro via the Adrenergic Receptor

2010

Self Cite

View full text Add to dashboard Cite

Abstract. There is currently great interest in the bone metabolism induced by the sympathetic nerve system. Recently, direct neurite-osteoblastic cell communication was demonstrated using an in vitro co-culture model comprising neurite-sprouting murine superior cervical ganglia and MC3T3-E1 osteoblast-like cells. In the present study, we examined whether the direct nerve-osteoclastic cell communication was present in an in vitro co-culture model comprising cultured murine superior cervical ganglia and mouse osteoclast-like cells. RAW264.7 cells treated with receptor activator of NF-κ B ligand were used as osteoclast-like cells. We found that the addition of scorpion venom (SV) elicited neurite activation via intracellular Ca 2+ mobilization and, after a lag period, osteoclastic Ca 2+ mobilization in the co-culture. SV did not have any direct effect on the osteoclastic cells in the absence of the neurites. The addition of an α 1 -adrenergic receptor (AR) antagonist, prazosin, concentration-dependently prevented the osteoclastic activation that resulted as a consequence of neural activation by SV. We also found that α 1 -adrenergic receptor agonists evoked transient Ca 2+ mobilization and gene expression of interleukin-6 in osteoclastic cells. These results demonstrate that osteoclastic activation occurs via α 1 -AR in osteoclastic cells as a direct response to neuronal activation.

show abstract

The role of the sympathetic nervous system in controlling bone metabolism

Cited by 75 publications

References 71 publications

Double disruption of α2A- and α2C -adrenoceptors results in sympathetic hyperactivity and high-bone-mass phenotype

Double disruption of α2A- and α2C -adrenoceptors results in sympathetic hyperactivity and high-bone-mass phenotype

Impact of substrate elasticity on human hematopoietic stem and progenitor cell adhesion and motility

Demonstration of Direct Neurite–Osteoclastic Cell Communication In Vitro via the Adrenergic Receptor

Contact Info

Product

Resources

About