Details

Autor(en) / Beteiligte

• Lai, Eddie Hsiang-Hua, DDS, MS
• Hong, Chi-Yuan, DDS, DMSc
• Kok, Sang-Heng, DDS, PhD
• Hou, Kuo-Liang, MS
• Chao, Ling-Hsiu, DDS
• Lin, Li-Deh, DDS, PhD
• Chen, Mu-Hsiung, BS
• Wu, Ping-Han, DDS, MS
• Lin, Sze-Kwan, DDS, PhD

Titel

Simvastatin Alleviates the Progression of Periapical Lesions by Modulating Autophagy and Apoptosis in Osteoblasts

Ist Teil von

• Journal of endodontics, 2012-06, Vol.38 (6), p.757-763

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2012

Quelle

MEDLINE

Beschreibungen/Notizen

• Abstract Introduction Autophagy is a process for recycling intracellular organelles as a survival mechanism. Apoptosis has important biological roles in the pathogenesis of many diseases. This study elucidated the effect of simvastatin on autophagy/apoptosis in MC3T3E1 murine osteoblastic cells and also the significance of this action on the progression of induced rat apical periodontitis. Methods We examined the H2O2-stimulated expression of LC3-II (an autophagy marker) and poly (adenosine phosphate ribose) polymerase (PARP) fragmentation (an apoptosis marker) in MC3T3E1 by Western analysis. In a rat model of induced apical periodontitis, the relation between disease progression and osteoblastic expression of Beclin-1 (an autophagy marker) and terminal deoxyuridine triphosphate nick end-labeling (an apoptosis marker) was studied by radiographic and immunohistochemistry analyses. Results Western blot showed elevated levels of LC3-II and PARP cleavage after H2O2 treatment. An autophagy inhibitor 3-methyladenine promoted whereas rapamycin (an autophagy enhancer) diminished H2O2-induced PARP cleavage. Simvastatin enhanced H2O2-induced LC3-II formation and simultaneously decreased PARP fragmentation. Radiography and immunohistopathology demonstrated that simvastatin reduced the number of apoptotic osteoblasts and the extension of periapical lesions in rats. The number of Beclin-1–synthesizing osteoblasts also increased markedly after simvastatin treatment. Conclusions We found a negative relation between autophagy and apoptosis in osteoblastic cells. In addition, simvastatin suppressed apoptosis and enhanced autophagy both in vitro and in vivo . Our data implied that simvastain might alleviate the progression of apical periodontitis by promoting autophagy to protect osteoblasts from turning apoptotic.