自噬通过 RANKL/RANK/OPG 轴调控实验性大鼠根尖周炎模型中的骨丢失。

Autophagy regulates bone loss via the RANKL/RANK/OPG axis in an experimental rat apical periodontitis model.

机构信息

State Key Laboratory of Oral Diseases & National Center for Stomatology & National Clinical Research Center for Oral Diseases & Frontier Innovation Center for Dental Medicine Plus, West China Hospital of Stomatology, Sichuan University, Chengdu, China.

出版信息

Int Endod J. 2024 Sep;57(9):1315-1325. doi: 10.1111/iej.14103. Epub 2024 Jun 24.

DOI:10.1111/iej.14103

PMID:38923421

Abstract

AIM

Autophagy is involved in human apical periodontitis (AP). However, it is not clear whether autophagy is protective or destructive in bone loss via the receptor activator of nuclear factor-κB ligand (RANKL)/RANK/osteoprotegerin (OPG) axis. This study aimed to investigate the involvement of autophagy via the RANKL/RANK/OPG axis during the development of AP in an experimental rat model.

METHODOLOGY

Twenty-four female Sprague-Dawley rats were divided into control, experimental AP (EAP) + saline, and EAP + 3-methyladenine (An autophagy inhibitor, 3-MA) groups. The control group did not receive any treatment. The EAP + saline group and the EAP + 3-MA group received intraperitoneal injections of saline and 3-MA, respectively, starting 1 week after the pulp was exposed. Specimens were collected for microcomputed tomography (micro-CT) scanning, histological processing, and immunostaining to examine the expression of light chain 3 beta (LC3B), RANK, RANKL, and OPG. Data were analysed using one-way analysis of variance (p < .05).

RESULTS

Micro-CT showed greater bone loss in the EAP + 3-MA group than in the EAP + saline group, indicated by an elevated trabecular space (Tb.Sp) (p < .05). Inflammatory cell infiltration was observed in the EAP + saline and EAP + 3-MA groups. Compared with EAP + saline group, the EAP + 3-MA group showed weaker expression of LC3B (p < .01) and OPG (p < .05), more intense expression of RANK (p < .01) and RANKL (p < .01), and a higher RANKL/OPG ratio (p < .05).

CONCLUSION

Autophagy may exert a protective effect against AP by regulating the RANKL/RANK/OPG axis, thereby inhibiting excessive bone loss.

摘要

目的

自噬参与了人根尖周炎（AP）。然而，自噬通过核因子-κB 受体激活物配体（RANKL）/RANK/骨保护素（OPG）轴在骨丢失中是保护还是破坏作用尚不清楚。本研究旨在通过核因子-κB 受体激活物配体（RANKL）/RANK/骨保护素（OPG）轴，探讨自噬在实验性大鼠根尖周炎（AP）发展过程中的作用。

方法

将 24 只雌性 Sprague-Dawley 大鼠分为对照组、实验性 AP（EAP）+生理盐水组和 EAP+3-甲基腺嘌呤（自噬抑制剂，3-MA）组。对照组未接受任何治疗。EAP+生理盐水组和 EAP+3-MA 组分别在牙髓暴露后 1 周时给予腹腔内注射生理盐水和 3-MA。收集标本进行微计算机断层扫描（micro-CT）扫描、组织学处理和免疫染色，以检测自噬相关蛋白微管相关蛋白轻链 3 （LC3B）、RANK、RANKL 和 OPG 的表达。采用单因素方差分析（p<0.05）进行数据分析。

结果

micro-CT 显示 EAP+3-MA 组较 EAP+生理盐水组的骨丢失更为严重，表现为骨小梁间隙（Tb.Sp）增加（p<0.05）。EAP+生理盐水组和 EAP+3-MA 组均可见炎性细胞浸润。与 EAP+生理盐水组相比，EAP+3-MA 组的 LC3B（p<0.01）和 OPG（p<0.05）表达较弱，RANK（p<0.01）和 RANKL（p<0.01）表达较强，RANKL/OPG 比值较高（p<0.05）。