[Effect of inferior alveolar nerve transection on mandibular condyles in rats and the repair effect of calcitonin gene-related peptide].

OBJECTIVE: To explore the impact of inferior alveolar nerve injury on mandibular condylar cartilage and condylar subchondral bone. And to further investigate the potential roles and molecular mechanisms of calcitonin gene-related peptide (CGRP) in condylar cartilage and subchondral bone.

METHODS: Sixty male 4-week-old Sprague-Dawley (SD) rats were randomly divided into three groups: a sham operation control group (only the right inferior alveolar nerve exposed and no other treatment was done), an inferior alveolar nerve transection (IANT) group (the right inferior alveolar nerve was transected more than 3 mm at the level of right mandibular oblique ridge), and a CGRP group (injection of 100 nmol/L CGRP into the right temporomandibular joint area after nerve transection, with 200 μL injections every three days for four weeks). Samples were collected at 1-, 2-, 4-, 6-, and 8-weeks post-surgery for analysis using a stereomicroscope, micro-CT, and histological staining to observe changes in the condylar cartilage and subchondral bone. Transcriptome sequencing and Western blot experiments were conducted on chondrocyte treated with CGRP (100 nmol/L) to analyze differences in gene and protein expression, as well as related biological processes and pathways. SPSS was used to analyze the differences between groups of the samples.

RESULTS: Compared with the sham operation group, alterations in the right condylar cartilage and subchondral bone were observable in the IANT group during the early phase of inferior alveolar nerve transection, specifically within the first week. For condylar cartilage, it could be observed that its overall thickness decreased, the surface fiber layer was incomplete, the pro-liferation layer cells decreased, and the hypertrophic cells increased relatively. For the subchondral bone of condyle, it could be seen that the head was narrowed, and the bone quality was worse than that of the sham group. In the CGRP group, the morphology of the condylar process, the thickness of the condylar cartilage layer, and the quality of the condylar subchondral bone were significantly better than those in the IANT group. In vitro cultured rat chondrocytes treated with CGRP were subjected to transcriptomic sequencing analysis, which suggested that CGRP might upregulate cartilage cell synthesis metabolism and cartilage-protective genes such as Col2a1 and Prg4 through pathways like phosphatidylinositol 3-kinase-protein kinase B (PI3K-Akt). After 7 days of CGRP induction, Western blot experiments revealed that CGRP had increased the expression of COL2A1 and SOX9 proteins.

CONCLUSION: Damage to the inferior alveolar nerve can cause degenerative changes in the condylar cartilage and subchondral bone. Injection of CGRP into the joint area can repair these damages to a certain extent. It is inferred that the injury of inferior alveolar nerve may lead to these negative changes by affecting the anabolism of chondrocytes, and CGRP may mitigate the effects of inferior alveolar nerve damage on the condylar cartilage and subchondral bone by activating signaling pathways such as PI3K-Akt in cartilage cells.