Selective β2-adrenergic Antagonist Butoxamine Reduces Orthodontic Tooth Movement

Sato, Takuma; Miyazawa, Ken; Suzuki, Yuki; Mizutani, Yusuke; Uchibori, S.; Asaoka, Ryo; Arai, M.; Togari, Akifumi; Goto, Shigemi

doi:10.1177/0022034514536730

Cited by 22 publications

(18 citation statements)

References 30 publications

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“…Adrb1/2 -/-mice showed a decrease in osteoclast differentiation and OTM distance. Although OTM distance may also be affected by other SNS-regulated activities, such as masticatory movement and alveolar bone density (Passatore and Roatta, 2007;Sato et al, 2014), our data provide a novel mechanism by which SNS-regulated OTM is mediated by force-induced Adrb2 activation. In previous studies, animal models were used to investigate the function of SNS in bone mechanoadaptive responses, such as tail suspension and sciatic neurectomy.…”

Section: Discussionmentioning

confidence: 85%

Force-induced Adrb2 in Periodontal Ligament Cells Promotes Tooth Movement

Cao¹,

Kou²,

Yang³

et al. 2014

J Dent Res

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The sympathetic nervous system (SNS) regulates bone resorption through β-2 adrenergic receptor (Adrb2). In orthodontic tooth movement (OTM), mechanical force induces and regulates alveolar bone remodeling. Compressive forceassociated osteoclast differentiation and alveolar bone resorption are the rate-limiting steps of tooth movement. However, whether mechanical force can activate Adrb2 and thus contribute to OTM remains unknown. In this study, orthodontic nickel-titanium springs were applied to the upper first molars of rats and Adrb1/2 -/-mice to confirm the role of SNS and Adrb2 in OTM. The results showed that blockage of SNS activity in the jawbones of rats by means of superior cervical ganglion ectomy reduced OTM distance from 860 to 540 μm after 14 d of force application. In addition, the injection of nonselective Adrb2 agonist isoproterenol activated the downstream signaling of SNS to accelerate OTM from 300 to 540 μm after 7 d of force application. Adrb1/2 -/-mice showed significantly reduced OTM distance (19.5 μm) compared with the wild-type mice (107.6 μm) after 7 d of force application. Histopathologic analysis showed that the number of Adrb2-positive cells increased in the compressive region of periodontal ligament after orthodontic force was applied on rats. Mechanistically, mechanical compressive force upregulated Adrb2 expression in primary-cultured human periodontal ligament cells (PDLCs) through the elevation of intracellular Ca 2+ concentration. Activation of Adrb2 in PDLCs increased the RANKL/OPG ratio and promoted the peripheral blood mononuclear cell differentiation to osteoclasts in the cocultured system. Upregulation of Adrb2 in PDLCs promoted osteoclastogenesis, which accelerated OTM through Adrb2-enhanced bone resorption. In summary, this study suggests that mechanical force-induced Adrb2 activation in PDLCs contributes to SNS-regulated OTM.

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Section: Discussionmentioning

confidence: 85%

Force-induced Adrb2 in Periodontal Ligament Cells Promotes Tooth Movement

Cao¹,

Kou²,

Yang³

et al. 2014

J Dent Res

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“…The sympathetic nervous system regulates bone metabolism by decreasing osteoblast activity and increasing osteoclast activity (Elefteriou et al, ; Togari & Arai, ; Takeda et al, ). Tooth movement is increased by increased bone metabolic turnover due to sympathetic activation (Kondo, Kondo, Miyazawa, Goto, & Togari, ; Sato et al, ). A previous study reported that spontaneously hypertensive rats (SHR) with sympathicotonia (Klemola, Huttunen, Laine, Weckström, & Hirvonen, ; Nagatsu et al, ; Wang, Hsu, Jee, & Matthews, ) have hypertension and osteoporosis due to decreased lumbar and tibial bone mass (Sato, Arai, Goto, & Togari, ).…”

Section: Introductionmentioning

confidence: 99%

“…A previous study reported that spontaneously hypertensive rats (SHR) with sympathicotonia (Klemola, Huttunen, Laine, Weckström, & Hirvonen, ; Nagatsu et al, ; Wang, Hsu, Jee, & Matthews, ) have hypertension and osteoporosis due to decreased lumbar and tibial bone mass (Sato, Arai, Goto, & Togari, ). It was recently reported that SHR with sympathicotonia result in increased tooth movement distance and decreased alveolar bone mass and that the selective β2‐adrenergic receptor (β2‐AR) blocker butoxamine decreases tooth movement and restores decreased maxillary alveolar bone volume (Sato et al, ). In the absence of tooth movement, alveolar bone formation did not differ between SHR and WKY, and bone resorption tended to be high, but alveolar bone mass did not change (Sato et al, ).…”

Section: Introductionmentioning

confidence: 99%

“…It was recently reported that SHR with sympathicotonia result in increased tooth movement distance and decreased alveolar bone mass and that the selective β2‐adrenergic receptor (β2‐AR) blocker butoxamine decreases tooth movement and restores decreased maxillary alveolar bone volume (Sato et al, ). In the absence of tooth movement, alveolar bone formation did not differ between SHR and WKY, and bone resorption tended to be high, but alveolar bone mass did not change (Sato et al, ).…”

Section: Introductionmentioning

confidence: 99%

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Suppression of tooth movement‐induced sclerostin expression using β‐adrenergic receptor blockers

et al. 2020

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Objective Regulation of bone metabolism by the sympathetic nervous system has recently been clarified. Tooth movement is increased by increased bone metabolic turnover due to sympathetic activation. This study aimed to compare the effects of the β‐adrenergic receptor (β‐AR) blockers atenolol (β1‐AR blocker), butoxamine (β2‐AR blocker) and propranolol (non‐selective β‐AR blocker) on tooth movement in spontaneously hypertensive rats (SHR) with sympathicotonia. Materials and Methods Spontaneously hypertensive rats were divided into the following four groups: an SHR control group and groups treated with 0.1 mg/kg atenolol, 1 mg/kg butoxamine or 1 mg/kg propranolol (n = 6 rats/group). Atenolol, butoxamine or propranolol was administered daily to each treatment group, and orthodontic force was applied using a closed‐coil spring. Finally, immunohistochemical analysis was performed for receptor activator of nuclear factor kappa‐B ligand (RANKL) and sclerostin (SOST). Results Atenolol, butoxamine and propranolol inhibited tooth movement and increased maxillary alveolar bone volume. Histological analysis revealed that these β‐AR blockers decreased osteoclast activity on the compression side. Furthermore, immunohistochemical analysis revealed that atenolol, butoxamine and propranolol decreased the number of RANKL‐ and SOST‐positive osteocytes on the compression side. Conclusions β‐AR blockers decreased tooth movement and downregulated SOST in osteocytes, accompanied by increasing alveolar bone resorption.

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“…Thus, application of mediators such as human growth hormone, nitric oxide, osteocalcin, parathyroid hormone, prostaglandins, and vitamin D has all shown to increase OTM . Conversely, in addition to OPG, bisphosphonates, butoxamine, echistatin, estradiol, MMP inhibitor, nitric oxide synthase inhibitor, and prostaglandin inhibitors contribute to decreased tooth movement . Further experiments are required to determine the optimal dosage and frequency, the efficiency of gene vs protein delivery, the determination of any systemic side effects, and the costs associated with such interventions prior to the utilization of biologic/pharmacologic agents as a part of standard orthodontic therapy.…”

Section: Precision Biomedicine In Orthodonticsmentioning

confidence: 99%

Moving towards precision orthodontics: An evolving paradigm shift in the planning and delivery of customized orthodontic therapy

Jheon

Oberoi

Solem

et al. 2017

Orthod Craniofacial Res

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Advances in precision medicine portend similar progress in orthodontics and will be increasingly harnessed to achieve customized treatment approaches and enhance treatment efficiencies. Our goal is to provide a background on emerging advances in computer technologies and biomedicine and highlight their current and likely future applications to precision orthodontics. A review of orthodontically relevant technologies and advances in pertinent biological research was undertaken. Innovations in computer hardware and software, and 3D imaging technologies offer the ability for customized treatment and biomechanical planning that will be more fully realized within the next few decades. These technologies combined with 3D printing are already being applied to customized appliance fabrication such as aligners and retainers. The future prospects for custom fabrication of orthodontic brackets of appropriate material properties and smart devices are highly desirable and compelling goals. Within biomedicine, the fundamental understanding of cartilage growth and bone biology is currently being tested in animal models to modify mandibular growth and modulate tooth movement, respectively. Some of these discoveries will ultimately have clinical applications in orthodontics including for growth modification, accelerating orthodontic tooth movement, and enhancing anchorage or retention of teeth. Additional genomic and proteomic information will add to further customization of orthodontic diagnosis and treatments. Over the coming decades, precision orthodontics will continue to benefit from advances in many fields and will require the integration of advances in technology, and biomedical and clinical research to deliver optimal, efficient, safe, and reproducible personalized orthodontic treatment.

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Selective β2-adrenergic Antagonist Butoxamine Reduces Orthodontic Tooth Movement

Cited by 22 publications

References 30 publications

Force-induced Adrb2 in Periodontal Ligament Cells Promotes Tooth Movement

Force-induced Adrb2 in Periodontal Ligament Cells Promotes Tooth Movement

Suppression of tooth movement‐induced sclerostin expression using β‐adrenergic receptor blockers

Moving towards precision orthodontics: An evolving paradigm shift in the planning and delivery of customized orthodontic therapy

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