Effect of sympathetic nervous activity on alveolar bone loss induced by occlusal hypofunction in rats
Introduction
Mechanical stimuli regulate the formation and maintenance of bone.1 Alveolar bone is considered to be an appropriate tissue for studying the mechanisms of structural changes in bone induced by mechanical stimuli because of its high turnover rate in response to mechanical loading including occlusal force.2 Occlusal force applied to teeth is transmitted to the alveolar/jaw bone through periodontal ligaments and maintains alveolar bone mass.3, 4, 5, 6, 7, 8 Under conditions of occlusal hypofunction, alveolar bone resorption is accelerated by an increase in osteoclasts via an osteoclast differentiation factor, receptor activator of nuclear factor kappa-B ligand (RANKL),3, 4, 5, 6 and bone formation is suppressed,7, 8 which depends on decreases in angiogenic activity and the production of vascular endothelial growth factor (VEGF) in the periodontium.9, 10
Bone mass and structure depend on the interaction of both osteoblasts and osteoclasts.11, 12, 13, 14 Bone formation and resorption are under the control of systemic hormones and local cytokines.11, 15 A previous study showed that the adipocyte-derived hormone leptin regulates bone formation via the sympathetic nervous system.16 The sympathetic nervous system controls bone resorption by increasing the expression of RANKL, via β2-adrenergic receptors in the leptin-dependent neuronal regulation of bone formation.17 Increased sympathetic nervous activity causes bone loss via an increase in bone resorption and a decrease in bone formation, which are associated with changes in β2-adrenergic activity that affect both osteoblasts and osteoclasts.18 Accordingly, β-adrenergic activity in the sympathetic nervous system plays a key role in both bone formation and resorption.
Moreover, a previous study showed that hindlimb unloading by tail suspension induces bone loss via the sympathetic nervous system.19 Sympathetic nervous activity mediates unloading-induced bone loss through the suppression of bone formation by osteoblasts and the enhancement of resorption by osteoclasts. However, the effect of sympathetic nervous activity on alveolar bone loss induced by occlusal hypofunction in rats is still not fully understood. Occlusal hypofunction decreases alveolar bone mass and accelerates bone resorption. Therefore, we hypothesized that modulation of the sympathetic nervous system via β-adrenergic receptors is involved in the metabolism of alveolar bone. In this study, we examined the effect of sympathetic nervous activity on occlusal hypofunction-induced alveolar bone loss in rats using a non-selective β-adrenergic receptor antagonist.
Section snippets
Experimental model
Twenty-four 5-week-old male Wistar rats were maintained under pathogen-free conditions and randomly divided into 4 groups; Groups C, H, B and HB. Group C was an untreated group that served as a control. In the occlusal hypofunction group (Group H), an anterior bite plate and a metal cap constructed from band material (0.180 in. × 0.005 in.; Rocky Mountain Morita, Tokyo, Japan) were attached to the maxillary and mandibular incisors, respectively, by means of light-curing composite resin (Clearfil
Body weight
The body weights of the rats were monitored throughout the experimental period. There were no significant changes in body weight in any of the groups during the course of the study.
Findings in micro-CT images of alveolar bone structure
Fig. 3 shows that the periodontal space in Groups H/HB was narrower than that in Groups C/B due to occlusal hypofunction. Trabecular bone in the interradicular septum in Group H was sparsely connected compared to that in Group C. Furthermore, that in Group HB was more densely compacted than that in Group H.
Quantitative evaluation of alveolar and tibial bone structure
In
Discussion
Mechanical stress acting on bone plays a crucial role in the maintenance of bone homeostasis, and a prolonged lack of mechanical stimulation leads to disuse osteoporosis.15, 23, 24, 25 The unloading of occlusal force on alveolar bone results in atrophic changes in alveolar bone and periodontal tissue.4, 5, 6, 7, 8, 20, 26, 27, 28, 29 Especially, bone formation was suppressed and bone resorption was significantly accelerated during the initial phase of occlusal hypofunction in rat models.4, 8
Acknowledgments
We wish to thank Dr. Masaki Yanagishita and Dr. Keiji Moriyama for their valuable advice.
Funding: This study was supported in part by Grants-in-Aid for Scientific Research (20592390, 20592393) from the Japanese Ministry of Education, Culture, Sports, Science and Technology.
Conflict of interest: None declared.
Ethical approval: The experimental procedures described here were approved by the Institutional Animal Care and Use Committee (#0110199A) and performed in accordance with the Animal Care
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