Simvastatin Promotes Cell Metabolism, Proliferation, and Osteoblastic Differentiation in Human Periodontal Ligament Cells

Yazawa, Hiroyuki; Zimmermann, Bernd; Asami, Yoshiko; Bernimoulin, Jean‐Pierre

doi:10.1902/jop.2005.76.2.295

Cited by 93 publications

(82 citation statements)

References 34 publications

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“…et al 6 stated the effect of SMV on human periodontal (PDL) cells in vitro and showed that, at a low concentration, SMV exhibits a positive effect on the proliferation and osteoblastic differentiation of human PDL cells, and these effects may be caused by inhibition of mevalonate pathway, indicating the role of SMV in bone regeneration. IL-6 and IL-8: In the present study, IL-6 and IL-8 levels are found to be higher in periodontitis patients, which is in accordance with studies done by Bartold et al 25 and Takahashi et al 26 This could be explained as Aggregatibacter actinomycetemcomitans and Campylobacter rectus have been shown to stimulate IL-6 and IL-8 production by human gingival fibroblasts.…”

Section: Discussionmentioning

confidence: 99%

“…4,5 Simvastatin (SMV), a synthetic statin, has a beneficial impact from a periodontal therapeutic standpoint on bone metabolism through osteoclast inactivation by affecting the generation of isoprenoids. 6 It has an anabolic effect and is a local stimulant for bone-growth regulatory factor. SMV also influences production of inflammatory cytokines via Creactive protein.…”

Section: Introductionmentioning

confidence: 99%

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Effect of topical simvastatin (1.2mg) on gingival crevicular fluid interleukin-6, interleukin-8 and interleukin-10 levels in chronic periodontitis – A clinicobiochemical study

Grover

Kapoor

Singh

2016

Journal of Oral Biology and Craniofacial Research

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CytokinesPeriodontal health GCF Host defence a b s t r a c tObjectives: The impact of simvastatin (SMV), a cholesterol lowering drug, on bone metabolism appears to involve complex interaction with cholesterol metabolites, hormones, inflammatory mediators and growth factors, thus having direct influence on extent and severity of periodontitis. The present study aims to evaluate the in vivo effect of subgingivally delivered SMV gel (1.2 mg) as a local drug-delivery agent on clinical parameters and on interleukin-6 (IL-6), interleukin-8 (IL-8) and interleukin-10 (IL-10) levels in gingival crevicular fluid (GCF) of chronic periodontitis patients. Materials and methods: 50 patients were selected and categorized into two treatment groups: control (scaling and root planing) and test group (scaling and root planing with SMV gel). At initial appointment, clinical parameters were measured. Biochemical analysis of GCF samples was done to evaluate the amount of IL-6, IL-8 and IL-10. GCF sampling and clinical parameters were repeated at one and three months for both the groups.Results: SMV has an inhibitory effect on pro-inflammatory cytokines (IL-6, IL-8) and stimulatory effect on anti-inflammatory cytokines (IL-10) in GCF of periodontitis patients and has significantly positive effect on all clinical parameters except relative attachment level (RAL).The addition of SMV, thereby, further alters the levels of cytokine that reflect enhanced antibacterial host defence activity at that site.Conclusion: Topical SMV has a beneficial effect on periodontal health. Removal of the bacterial plaque and subgingival delivery of SMV significantly modulates the chemokines present in GCF. To summarize, SMV shows promising role in the management of periodontitis.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Effect of topical simvastatin (1.2mg) on gingival crevicular fluid interleukin-6, interleukin-8 and interleukin-10 levels in chronic periodontitis – A clinicobiochemical study

Grover

Kapoor

Singh

2016

Journal of Oral Biology and Craniofacial Research

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“…Cerivastatin was the most potent agent, while pravastatin was unable to stimulate BMP-2 promoter activity and new bone formation in neonatal murine calvaria (Garrett et al 2001b). Investigation of the effects of simvastatin on cell proliferation and osteoblastic differentiation in human periodontal ligament (PDL) cells showed that simvastatin enhanced cell proliferation and alkaline phosphatase activity in a dose-dependent fashion (Yazawa et al 2005). Maeda et al (2001) studied the effect of simvastatin on osteoblast differentiation and function using a nontransformed osteoblast (MC3T3-E1) cell line and rat bone marrow cells.…”

Section: In-vitro Studiesmentioning

confidence: 99%

Statins and osteoporosis: new role for old drugs

Jadhav

Jain

2006

Journal of Pharmacy and Pharmacology

145

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Osteoporosis is the most common bone disease, affecting millions of people worldwide and leading to significant morbidity and high expenditure. Most of the current therapies available for its treatment are limited to the prevention or slowing down of bone loss rather than enhancing bone formation. Recent discovery of statins (HMG-CoA reductase inhibitors) as bone anabolic agents has spurred a great deal of interest among both basic and clinical bone researchers. In-vitro and some animal studies suggest that statins increase the bone mass by enhancing bone morphogenetic protein-2 (BMP-2)-mediated osteoblast expression. Although a limited number of case-control studies suggest that statins may have the potential to reduce the risk of fractures by increasing bone formation, other studies have failed to show a benefit in fracture reduction. Randomized, controlled clinical trials are needed to resolve this conflict. One possible reason for the discrepancy in the results of preclinical, as well as clinical, studies is the liver-specific nature of statins. Considering their high liver specificity and low oral bioavailability, distribution of statins to the bone microenvironment in optimum concentration is questionable. To unravel their exact mechanism and confirm beneficial action on bone, statins should reach the bone microenvironment in optimum concentration. Dose optimization and use of novel controlled drug delivery systems may help in increasing the bioavailability and distribution of statins to the bone microenvironment. Discovery of bone-specific statins or their bone-targeted delivery offers great potential in the treatment of osteoporosis. In this review, we have summarized various preclinical and clinical studies of statins and their action on bone. We have also discussed the possible mechanism of action of statins on bone. Finally, the role of drug delivery systems in confirming and assessing the actual potential of statins as anti-osteoporotic agents is highlighted.

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“…Statins are specific inhibitors of 3-hydroxy-3methyl-glutaryl coenzyme A (HMGCoA) reductase and are some of the most used drugs in the treatment of atherosclerosis and other cardiovascular conditions [Pedersen et al 1996]. Recent in vitro research has indicated an anabolic effect of these drugs on bone [Yazawa et al 2005]. Moreover, simvastatin was found to enhance bone formation through induction of BMP-2 and alkaline phosphatase and by the accumulation of bone matrix proteins [Maeda et al 2001].…”

Section: The Current Status Of 'Old Drugs For New Applications'mentioning

confidence: 99%

‘Old Drugs for New Applications’: Can Orthopedic Research Benefit from This Strategy?

Pan

Cheng

Wang

et al. 2011

Therapeutic Advances in Musculoskeletal

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New drug exploration is difficult in a clinical setting and the development of new drugs may be costly and time consuming. With further research into the pathological mechanisms and etiology of diseases as well as the rapid development of biological techniques, many 'old drugs' that have been applied in clinics may have new therapeutic functions which may shed light on clinical management. Based on this, we have investigated the 'old drugs for new applications' strategy in pharmacology which may be less expensive and more efficient in the clinical setting. In this paper we have explored and illustrated the potential applications of 'old drugs' for the treatment of orthopedic diseases, especially in arthritis and osteoporosis therapy.

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Simvastatin Promotes Cell Metabolism, Proliferation, and Osteoblastic Differentiation in Human Periodontal Ligament Cells

Abstract: These results suggest that at low concentration, simvastatin exhibits positive effect on proliferation and osteoblastic differentiation of human PDL cells, and these effects may be caused by the inhibition of the mevalonate pathway.

Cited by 93 publications

References 34 publications

Effect of topical simvastatin (1.2mg) on gingival crevicular fluid interleukin-6, interleukin-8 and interleukin-10 levels in chronic periodontitis – A clinicobiochemical study

Effect of topical simvastatin (1.2mg) on gingival crevicular fluid interleukin-6, interleukin-8 and interleukin-10 levels in chronic periodontitis – A clinicobiochemical study

Statins and osteoporosis: new role for old drugs

‘Old Drugs for New Applications’: Can Orthopedic Research Benefit from This Strategy?

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