Simvastatin intervention mitigates hypercholesterolemia‑induced alveolar bone resorption in rats

Gao,Xiaoli; Zhou,Jianhua; Bian,Yuanyuan; Huang,Shengyun; Zhang,Dongsheng

doi:10.3892/etm.2021.10060

Simvastatin intervention mitigates hypercholesterolemia‑induced alveolar bone resorption in rats

Authors:
- Xiaoli Gao
- Jianhua Zhou
- Yuanyuan Bian
- Shengyun Huang
- Dongsheng Zhang
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Affiliations: 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 Stomatology, Qingdao Municipal Hospital, Qingdao, Shandong 266071, P.R. China, Department of Oral and Maxillofacial Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong 250021, P.R. China
Published online on: April 15, 2021 https://doi.org/10.3892/etm.2021.10060
Article Number: 628
Copyright: © Gao et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

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.

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