Identification of Genes Differentially Expressed in Simvastatin-Induced Alveolar Bone Formation

J. Liu, S. K. Chanumolu, Z. Krei, M. Albahrani, A. Akhtam, Z. Jia, X. Wang, D. Wang, H. H. Otu, R. A. Reinhardt, A. Nawshad

Research output: Contribution to journalArticlepeer-review

5 Scopus citations

Abstract

Local delivery of simvastatin (SIM) has exhibited potential in preventing inflammation and limiting bone loss associated with experimental periodontitis. The primary aim of this study was to analyze transcriptome changes that may contribute to SIM's reduction of periodontal inflammation and bone loss. We evaluate the global genetic profile and signaling mechanisms induced by SIM on experimental periodontitis bone loss and inflammation. Twenty mature female Sprague Dawley rats were subjected to ligature-induced experimental periodontitis around maxillary second molars (M2) either unilaterally (one side untreated, n = 10) or bilaterally (n = 10). After the ligature removal at day 7, sites were injected with either carrier, pyrophosphate (PPi ×3), 1.5-mg SIM-dose equivalent SIM-pyrophosphate prodrug, or no injection. Three days after ligature removal, animals were euthanized; the M1-M2 interproximal was evaluated with μCT, histology, and protein expression. M2 palatal gingiva was harvested for RNA sequencing. Although ligature alone caused upregulation of proinflammatory and bone catabolic genes and proteins, seen in human periodontitis, SIM-PPi upregulated anti-inflammatory (IL-10, IL-1 receptor-like 1) and bone anabolic (insulin-like growth factor, osteocrin, fibroblast growth factor, and Wnt/ β-catenin) genes. The PPi carrier alone did not have these effects. Genetic profile and signaling mechanism data may help identify enhanced pharmacotherapeutic approaches to limit or regenerate periodontitis bone loss.

Original languageEnglish (US)
Article numbere10122
JournalJBMR Plus
Volume3
Issue number5
DOIs
StatePublished - May 2019

Keywords

  • ANABOLICS
  • DENTAL BIOLOGY
  • GH/IGF-1
  • MOLECULAR PATHWAYS–REMODELING
  • WNT/Β-CATENIN/LRPS

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Orthopedics and Sports Medicine

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