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Age-dependent impact of inferior alveolar nerve transection on mandibular bone metabolism and the underlying mechanisms

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Abstract

Aging is associated with peripheral nerve degradation and bone destruction. The aim of the study is to elucidate the influence of sensory denervation on bone metabolism in different age groups by establishing a modified unilateral inferior alveolar nerve transection (IANT) model. The rats, divided into young, middle-aged and aged group, were sacrificed at 1, 2, 4 and 8 weeks after right IANT. The histological changes of mandibles were analyzed by fluorescent double labeling, micro-CT, HE, TRAP and anti-CGRP immunohistochemical staining. Molecular mechanisms underlying the changes were analyzed by qPCR and western blot. Differences between the test and control side were evaluated by paired-samples t test. The Friedman test and separate Wilcoxon signed-rank tests were applied to analyze age-dependent difference. The impact of IANT was the most intensive in developing bone, the most persistent in full grown bone and the faintest in the aged bone. The role of IAN in keeping homeostasis was closely related to the anabolic effect of CGRP, which suppressed the number of osteoclasts through OPG/RANKL ratio and controlled growth factors expression like BMP2. This study contributes to a better understanding of the molecular mechanisms of CGRP in vivo and the relationship among sensory nerve, bone metabolism and aging.

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References

  • Adam C, Llorens A, Baroukh B, Cherruau M, Saffar J (2000) Effects of capsaicin-induced sensory denervation on osteoclastic resorption in adult rats. Exp Physiol 85:61–66

    Article  CAS  Google Scholar 

  • Atsumi Y, Imai T, Matsumoto K, Sakuda M, Kurisu K, Wakisaka S (2000) Effects of neonatal injury of the inferior alveolar nerve on the development and regeneration of periodontal nerve fibers in the rat incisor. Brain Res 871:201–209

    Article  CAS  PubMed  Google Scholar 

  • Berger C et al (2008) Change in bone mineral density as a function of age in women and men and association with the use of antiresorptive agents. Can Med Assoc J 178:1660–1668

    Article  Google Scholar 

  • Blain H et al (2008) Cortical and trabecular bone distribution in the femoral neck in osteoporosis and osteoarthritis. Bone 43:862–868

    Article  CAS  PubMed  Google Scholar 

  • Bo Y, Yan L, Gang Z, Tao L, Yinghui T (2012) Effect of calcitonin gene-related peptide on osteoblast differentiation in an osteoblast and endothelial cell co-culture system. Cell Biol Int 36:909–915

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bucelli RC, Gonsiorek EA, Kim W-Y, Bruun D, Rabin RA, Higgins D, Lein PJ (2008) Statins decrease expression of the proinflammatory neuropeptides calcitonin gene-related peptide and substance P in sensory neurons. J Pharmacol Exp Ther 324:1172–1180

    Article  CAS  PubMed  Google Scholar 

  • Ceballos D, Cuadras J, Verdú E, Navarro X (1999) Morphometric and ultrastructural changes with ageing in mouse peripheral nerve. J Anat 195:563–576

    Article  PubMed  PubMed Central  Google Scholar 

  • Ding Y, Arai M, Kondo H, Togari A (2010) Effects of capsaicin-induced sensory denervation on bone metabolism in adult rats. Bone 46:1591–1596

    Article  CAS  PubMed  Google Scholar 

  • Hill E, Turner R, Elde R (1991) Effects of neonatal sympathectomy and capsaicin treatment on bone remodeling in rats. Neuroscience 44:747–755

    Article  CAS  PubMed  Google Scholar 

  • Hukkanen M, Konttinen Y, Santavirta S, Paavolainen P, Gu X-H, Terenghi G, Polak J (1993) Rapid proliferation of calcitonin gene-related peptide-immunoreactive nerves during healing of rat tibial fracture suggests neural involvement in bone growth and remodelling. Neuroscience 54:969–979

    Article  CAS  PubMed  Google Scholar 

  • Jacobsen EB, Heyeraas KJ (1996) Effect of capsaicin treatment or inferior alveolar nerve resection on dentine formation and calcitonin gene-related peptide-and substance P-immunoreactive nerve fibres in rat molar pulp. Arch Oral Biol 41:1121–1131

    Article  CAS  PubMed  Google Scholar 

  • Lerner UH, Persson E (2008) Osteotropic effects by the neuropeptides calcitonin gene-related peptide, substance P and vasoactive intestinal peptide. J Musculoskelet Neuronal Interact 8:154–165

    CAS  PubMed  Google Scholar 

  • Lin M-H, Mau L-P, Cochran DL, Shieh Y-S, Huang P-H, Huang R-Y (2014) Risk assessment of inferior alveolar nerve injury for immediate implant placement in the posterior mandible: a virtual implant placement study. J Dent 42:263–270

    Article  PubMed  Google Scholar 

  • Lv L, Wang Y, Zhang J, Zhang T, Li S (2014) Healing of periodontal defects and calcitonin gene related peptide expression following inferior alveolar nerve transection in rats. J Mol Histol 45:311–320

    Article  CAS  PubMed  Google Scholar 

  • Mrak E, Guidobono F, Moro G, Fraschini G, Rubinacci A, Villa I (2010) Calcitonin gene-related peptide (CGRP) inhibits apoptosis in human osteoblasts by β-catenin stabilization. J Cell Physiol 225:701–708

    Article  CAS  PubMed  Google Scholar 

  • Offley SC et al (2005) Capsaicin-sensitive Sensory neurons contribute to the maintenance of trabecular bone integrity. J Bone Miner Res 20:257–267

    Article  PubMed  Google Scholar 

  • Pang P, Shimo T, Takada H, Matsumoto K, Yoshioka N, Ibaragi S, Sasaki A (2015) Expression pattern of sonic hedgehog signaling and calcitonin gene-related peptide in the socket healing process after tooth extraction. Biochem Biophys Res Commun 467:21–26

    Article  CAS  PubMed  Google Scholar 

  • Rivner MH, Swift TR, Malik K (2001) Influence of age and height on nerve conduction. Muscle Nerve 24:1134–1141

    Article  CAS  PubMed  Google Scholar 

  • Santos MI, Unger RE, Sousa RA, Reis RL, Kirkpatrick CJ (2009) Crosstalk between osteoblasts and endothelial cells co-cultured on a polycaprolactone–starch scaffold and the in vitro development of vascularization. Biomaterials 30:4407–4415

    Article  CAS  PubMed  Google Scholar 

  • Sauer S, Reeh P, Bove G (2001) Noxious heat-induced CGRP release from rat sciatic nerve axons in vitro. Eur J Neurosci 14:1203–1208

    Article  CAS  PubMed  Google Scholar 

  • Song Q, Li S, Patil PM (2014) Inferior alveolar and mental nerve injuries associated with open reduction and internal fixation of mandibular fractures: a 7 years retrospective study. J Cranio-Maxillofac Surg 42:1378–1381

    Article  Google Scholar 

  • Sun Y, Tao R, Zhang M, Cao X, Wang H, Xue L, Wu M (2013) Expression of calcitonin gene-related peptide in rat pulp and periodontal tissues by indirect immunofluorescence method. Monoclon Antib Immunodiagn Immunother 32:404–408

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Szolcsányi J (2004) Forty years in capsaicin research for sensory pharmacology and physiology. Neuropeptides 38:377–384

    Article  CAS  PubMed  Google Scholar 

  • Togari A, Arai M (2008) Pharmacological topics of bone metabolism: the physiological function of the sympathetic nervous system in modulating bone resorption. J Pharmacol Sci 106:542–546

    Article  CAS  PubMed  Google Scholar 

  • Tuo Y et al (2013) The biological effects and mechanisms of calcitonin gene-related peptide on human endothelial cell. J Recept Signal Transduct 33:114–123

    Article  CAS  Google Scholar 

  • Ward KA et al (2011) Influence of age and sex steroids on bone density and geometry in middle-aged and elderly European men. Osteoporos Int 22:1513–1523

    Article  CAS  PubMed  Google Scholar 

  • Wimalawansa SJ (1996) Calcitonin gene-related peptide and its receptors: molecular genetics, physiology, pathophysiology, and therapeutic potentials. Endocr Rev 17:533–585

    Article  CAS  PubMed  Google Scholar 

  • Wu M, Zhao Z, Han Y (2014) The changes of Proteome in MG-63 cells after induced by calcitonin gene-related peptide. Biochem Biophys Res Commun 453:648–652

    Article  CAS  PubMed  Google Scholar 

  • Xu G, Jiang D (2014) The role and mechanism of exogenous calcitonin gene-related peptide on mesenchymal stem cell proliferation and osteogenetic formation. Cell Biochem Biophys 69:369–378

    Article  CAS  PubMed  Google Scholar 

  • Yamashiro T, Fujiyama K, Fujiyoshi Y, Inaguma N, Takano-Yamamoto T (2000) Inferior alveolar nerve transection inhibits increase in osteoclast appearance during experimental tooth movement. Bone 26:663–669

    Article  CAS  PubMed  Google Scholar 

  • Ye F et al (2007) Involvement of endothelial cell-derived CGRP in heat stress-induced protection of endothelial function. Vascul Pharmacol 46:238–246

    Article  CAS  PubMed  Google Scholar 

  • Yu X, Lv L, Zhang J, Zhang T, Xiao C, Li S (2015) Expression of neuropeptides and bone remodeling-related factors during periodontal tissue regeneration in denervated rats. J Mol Histol 46:195–203

    Article  CAS  PubMed  Google Scholar 

  • Zhou Z, Yin Y, Jiang F, Niu Y, Wan S, Chen N, Shen M (2016) CBX7 deficiency plays a positive role in dentin and alveolar bone development. J Mol Histol 47:401–411

    Article  CAS  PubMed  Google Scholar 

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Acknowledgments

This study was supported by National Natural Science Foundation (No. 81170995).

Funding

This study was supported by National Key Clinical Speciality on Oral Implantology, National Science Foundation (No. 81170995).

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Correspondence to Ping Gong.

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Wu, Q., Yang, B., Cao, C. et al. Age-dependent impact of inferior alveolar nerve transection on mandibular bone metabolism and the underlying mechanisms. J Mol Hist 47, 579–586 (2016). https://doi.org/10.1007/s10735-016-9697-9

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  • DOI: https://doi.org/10.1007/s10735-016-9697-9

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