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. © 2018 The Authors. JBMR Plus Published by Wiley Periodicals, Inc. on behalf of the American Society for Bone and
Mineral Research.