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Lactone form 3‐hydroxy‐3‐methylglutaryl‐coenzyme A reductase inhibitors (statins) stimulate the osteoblastic differentiation of mouse periodontal ligament cells via the ERK pathway
Author(s) -
Kim I. S.,
Jeong B. C.,
Kim O. S.,
Kim Y. J.,
Lee S. E.,
Lee K. N.,
Koh J. T.,
Chung H. J.
Publication year - 2011
Publication title -
journal of periodontal research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.31
H-Index - 83
eISSN - 1600-0765
pISSN - 0022-3484
DOI - 10.1111/j.1600-0765.2010.01329.x
Subject(s) - bone sialoprotein , osteocalcin , lovastatin , simvastatin , chemistry , periodontal fiber , osteoblast , alkaline phosphatase , endocrinology , medicine , dentin sialophosphoprotein , biochemistry , biology , cholesterol , dentistry , enzyme , in vitro
Kim IS, Jeong BC, Kim OS, Kim YJ, Lee SE, Lee KN, Koh JT, Chung HJ. Lactone form 3‐hydroxy‐3‐methylglutaryl‐coenzyme A reductase inhibitors (statins) stimulate the osteoblastic differentiation of mouse periodontal ligament cells via the ERK pathway. J Periodont Res 2011; 46: 204–213. © 2010 John Wiley & Sons A/SBackground and Objective: Recent studies reported that the lactone forms of 3‐hydroxy‐ 3‐methylglutaryl‐coenzyme A reductase inhibitors, which are also known as statins, have a bone stimulatory effect. However, there are few reports on the effect of statins on periodontal ligament cells. This study examined the statin‐induced osteoblastic differentiation of mouse periodontal ligament cells as well as its mechanism. Material and Methods: Mouse periodontal ligament cells were cultured with lovastatin or simvastatin, and their viability was measured. The levels of alkaline phosphatase (ALP), osteocalcin, bone sialoprotein and bone morphogenetic protein‐2 mRNA expression were evaluated by RT‐PCR. The osteoblastic differentiation was characterized by the ALP activity and Alizarin Red‐S staining for calcium deposition. The activity of the osteocalcin gene ( OG2 ) and synthetic osteoblast‐specific elements (6× OSE ) promoter with statins was also measured using a luciferase assay. For the signal mechanism of statins, the ERK1/2 MAPK activity was determined by western blot analysis. Results: A statin treatment at concentrations < 1 μ m did not affect the cell viability. Lovastatin or simvastatin at 0.1 μ m increased the levels of ALP, osteocalcin, bone sialoprotein and bone morphogenetic protein‐2 mRNA in mouse periodontal ligament cells. In addition, the ALP activity, mineralized nodule formation and OG2 and OSE promoter activity were higher in the lovastatin‐ or simvastatin‐treated cells than the control cells. Western blot analysis confirmed that the statins stimulated the phosphorylation of ERK1/2. Conclusion: Lovastatin and simvastatin may stimulate the osteoblastic differentiation of periodontal ligament cells via the ERK1/2 pathway. This suggests that the statins may be useful for regenerating periodontal hard tissue.