Local delivery of simvastatin maintains tooth anchorage during mechanical tooth moving via anti-inflammation property and AMPK/MAPK/NF-kB inhibition

Lianyi Xu, Xiaojuan Sun, Guangxun Zhu, Jing Mao, Babak Baban, Xu Qin

Research output: Contribution to journalArticlepeer-review

Abstract

Simvastatin (SMV) could increase tooth anchorage during orthodontic tooth movement (OTM). However, previous studies on its bone-specific anabolic and anti-inflammation properties were based on static in vitro and in vivo conditions. AMPK is a stress-activated kinase that protects tissue against serious damage from overloading inflammation. Rat periodontal ligament cells (PDLCs) were subjected to a serial of SMV concentrations to investigate the optimization that promoted osteogenic differentiation. The PDLCs in static and/or tensile culturing conditions then received the proper concentration SMV. Related factors expression was measured by the protein array, real-time PCR and Western blot. The 0.05UM SMV triggered osteogenic differentiation of PDLCs. The inhibition of AMPK activation through a pharmacological approach (Compound C) caused dramatic decrease in osteogenic/angiogenic gene expression and significant increase in inflammatory NF-κB phosphorylation. In contrast, pharmacological activation of AMPK by AICAR significantly inhibited inflammatory factors expression and activated ERK1/2, P38 MAPK phosphorylation. Moreover, AMPK activation induced by SMV delivery significantly attenuated the osteoclastogenesis and decreased the expression of pro-inflammatory TNF-α and NF-κB in a rodent model of OTM. The current studies suggested that SMV could intrigue intrinsic activation of AMPK in PDLCs that promote attenuate the inflammation which occurred under tensile irritation through AMPK/MAPK/NF-kB Inhibition.

Original languageEnglish (US)
Pages (from-to)333-344
Number of pages12
JournalJournal of Cellular and Molecular Medicine
Volume25
Issue number1
DOIs
StatePublished - Jan 2021

Keywords

  • AMPK
  • MAPK
  • animal study
  • mechanical stress
  • periodontal ligament cells
  • simvastatin

ASJC Scopus subject areas

  • Molecular Medicine
  • Cell Biology

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