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

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.

Inferior alveolar nerve transection disturbs innate immune responses and bone healing after tooth extraction

“…Previously, we observed that IANT led to the breakdown of the distal nerve endings, triggered an acute neuropeptide shortage, and resulted in a sharp increase in the nociceptive threshold . In the current study, surgical sensory denervation triggered a disturbance of normal bone remodeling involving the bone formation rate (Fig.…”

“…Thirty‐six 20‐week‐old male C57Bl/6J mice were acclimated for 1 week before surgery. A sensory denervation model was performed in the current study. Briefly, a skin incision along the middle one‐third of the lower mandible margin was performed after anesthetization.…”

“…Abundant sensory fibers derived from the inferior alveolar nerve (IAN) are distributed throughout the mandible, and denervation by inferior alveolar nerve transection (IANT) can complicate bone healing . The oral mucosa lining the alveolar bone faces an environment highly susceptible to microbial challenges, mechanical irritations, and surgical wounds .…”

“…IANT is a classical sensory denervation model for studying sensory–bone communications in jaw bones . Nerve endings of the IAN suffer degradation after injury, causing reduction in the release of sensory neurotransmitters and affecting the balance of bone metabolism .…”

“…IANT is a classical sensory denervation model for studying sensory–bone communications in jaw bones . Nerve endings of the IAN suffer degradation after injury, causing reduction in the release of sensory neurotransmitters and affecting the balance of bone metabolism . Calcitonin gene‐related peptide (CGRP), one of the classical sensory neurotransmitters, is closely associated with sensory–immune crosstalk .…”