Gao Xiaoli, Zhou Jianhua, Bian Yuanyuan, Huang Shengyun, Zhang Dongsheng
Department of Oral and Maxillofacial Surgery, School and Hospital of Stomatology, Shangdong University and Shandong Provincial Key Laboratory of Oral Tissue Regeneration and Shandong Engineering Laboratory for Dental Materials and Oral Tissue Regeneration, Jinan, Shandong 250012, P.R. China.
Department of Oral and Maxillofacial Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong 250021, P.R. China.
Exp Ther Med. 2021 Jun;21(6):628. doi: 10.3892/etm.2021.10060. Epub 2021 Apr 15.
Simvastatin promotes bone formation and increases bone mineral density in patients with hyperlipidemia and ameliorates hypercholesterolemia-induced microstructure changes in the jaw bone of animals. However, whether and how treatment with simvastatin can modulate the hypercholesterolemia-induced alveolar bone resorption is unclear. The present study aimed to examine the therapeutic efficacy and potential mechanisms of simvastatin application in hypercholesterolemia-induced alveolar bone resorption. The association between hyperlipidemia and alveolar bone resorption in 100 patients with periodontitis was examined. Additionally, male Sprague-Dawley rats were fed a standard rodent chow (NC) for 32 weeks or a high cholesterol diet (HCD) for 24 weeks. The HCD-fed rats were randomized, continually fed with HCD and treated with vehicle saline (HC) or simvastatin by gavage (5 mg/kg; SIM, n=10/group) for 8 weeks. The morphological changes to alveolar bone resorption in rats were analyzed by linear measurements. The relative levels of osteoprotegerin (OPG), receptor activator of nuclear factor-κB ligand RANKL, nuclear factor-κB (NF-κB), microtubule-associated protein 1 light chain 3 (LC3) and p62 in the alveolar bone tissues were determined by reverse transcription-quantitative PCR and/or immunohistochemistry. Sulcus bleeding index (SBI), clinical attachment loss (CAL), probing depth (PD) and the distance of cemantoenamel junction-alveolar bone crest (CEJ-ABC) in patients with hyperlipidemia were significantly greater than that in the controls (P<0.001). The levels of hyperlipidemia were positively correlated with the values of SBI, CAL, PD and CEJ-ABC in this population. Compared with the NC rats, higher levels of alveolar bone resorption, NF-κB expression, higher ratios of RANKL/OPG mRNA transcripts and LC3 to p62 expression were detected in the alveolar bone tissues of HC group. Simvastatin intervention significantly mitigated hypercholesterolemia-induced alveolar bone loss and RANKL mRNA transcription, but increased the ratios of LC3/p62 protein expression in the alveolar bone tissues of rats. Hyperlipidemia is associated with alveolar bone resorption and simvastatin treatment alleviated the hypercholesterolemia-related alveolar bone loss by down-regulating the NF-κB expression.
辛伐他汀可促进高脂血症患者的骨形成并增加骨密度，改善高胆固醇血症诱导的动物颌骨微观结构变化。然而，辛伐他汀治疗是否以及如何调节高胆固醇血症诱导的牙槽骨吸收尚不清楚。本研究旨在探讨辛伐他汀在高胆固醇血症诱导的牙槽骨吸收中的治疗效果及潜在机制。检测了100例牙周炎患者高脂血症与牙槽骨吸收之间的关联。此外，将雄性Sprague-Dawley大鼠喂饲标准啮齿动物饲料（NC）32周或高胆固醇饮食（HCD）24周。将喂饲HCD的大鼠随机分组，继续喂饲HCD，并通过灌胃给予溶媒盐水（HC）或辛伐他汀（5 mg/kg；SIM，每组n = 10）8周。通过线性测量分析大鼠牙槽骨吸收的形态学变化。采用逆转录定量PCR和/或免疫组织化学法测定牙槽骨组织中骨保护素（OPG）、核因子κB受体活化因子配体RANKL、核因子κB（NF-κB）、微管相关蛋白1轻链3（LC3）和p62的相对水平。高脂血症患者的龈沟出血指数（SBI）、临床附着丧失（CAL）、探诊深度（PD）以及牙骨质釉质界至牙槽嵴顶的距离（CEJ-ABC）均显著大于对照组（P<0.001）。该人群中高脂血症水平与SBI、CAL、PD及CEJ-ABC值呈正相关。与NC组大鼠相比，HC组大鼠牙槽骨组织中牙槽骨吸收水平、NF-κB表达、RANKL/OPG mRNA转录物及LC3与p62表达的比值更高。辛伐他汀干预显著减轻了高胆固醇血症诱导的牙槽骨丢失和RANKL mRNA转录，但增加了大鼠牙槽骨组织中LC3/p62蛋白表达的比值。高脂血症与牙槽骨吸收相关，辛伐他汀治疗通过下调NF-κB表达减轻了高胆固醇血症相关的牙槽骨丢失。
