Protective Effect of Metformin on Periapical Lesions in Rats by Decreasing the Ratio of Receptor Activator of Nuclear Factor Kappa B Ligand/Osteoprotegerin

Liu, Lingshuang; Zhang, Chi; Hu, Yuanming; Peng, Bin

doi:10.1016/j.joen.2012.03.010

Cited by 72 publications

(76 citation statements)

References 32 publications

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“…Experimental periapical lesion induction can be achieved using several methods, such as pulpal perforation (Liu et al . , Wolle et al . ) or pulpal stimulation with lipopolysaccharide (LPS) or other endodontic pathogens (Fukada et al .…”

Section: Discussionmentioning

confidence: 96%

“…), anti‐hyperglycaemic agents (Liu et al . ), bisphosphonates (Wayama et al . ), selective oestrogen receptor modulators (Gomes‐Filho et al .…”

Section: Discussionmentioning

confidence: 99%

“…In the present study, because of the evaluation of tissue reactions in the lesions, immunohistochemistry was preferred over PCR as in previous studies (Liu et al . , Chuang et al . , Bezerra da Silva et al .…”

Section: Discussionmentioning

confidence: 99%

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Anti‐inflammatory and antiresorptive functions of melatonin on experimentally induced periapical lesions

Sarıtekin¹,

Kaya²,

Aşçı³

et al. 2019

Int Endodontic J

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Aim To investigate the effects of systemically administered melatonin on inflammation and alveolar bone resorption in rats with experimentally induced periapical lesions. Methodology Thirty adult Sprague Dawley rats were divided equally into negative, positive control and melatonin groups. The pulp chambers of their mandibular first molars were exposed to the oral environment to induce experimental periapical lesions in the positive control and melatonin groups. The melatonin group received daily intraperitoneal injections of melatonin at a dose of 10 mg kg−1. After 21 days, the animals were euthanized; the hemi‐mandible parts were prepared for radiological, histopathological, immunohistochemical (IL‐1β, RANK, RANKL, OPG and tartrate‐resistant acid phosphatase (TRAP) and Brown–Brenn (bacteria) evaluations. Data were analysed by Kruskal–Wallis (for non‐parametric data) and one‐way anova tests (for parametric data) (P < 0.05). Results The area of radiographic periapical bone loss was significantly smaller in rats that were given daily intraperitoneal injections of melatonin (P < 0.01). The histopathological scores of the melatonin group were significantly lower than those of positive control group (P < 0.01). Histomorphometrically, the area of periapical bone loss in the melatonin group was significantly smaller than the positive control group (P < 0.01). The expression of IL1‐β, RANK and RANKL was significantly higher in the positive control group, whereas OPG was significantly higher in the melatonin group (P < 0.01). The number of osteoclasts was significantly greater in the positive control group by TRAP staining analyses (P < 0.01). The scores for bacteria localization using Brown–Brenn staining in the melatonin group was significantly lower than that of the positive control group (P < 0.01). Conclusions Melatonin demonstrated antiresorptive effects on bone associated with experimentally induced periapical lesions in rats via its anti‐inflammatory activity. Further studies are necessary to evaluate its possible effects on the healing of periapical lesions.

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Section: Discussionmentioning

confidence: 96%

“…), anti‐hyperglycaemic agents (Liu et al . ), bisphosphonates (Wayama et al . ), selective oestrogen receptor modulators (Gomes‐Filho et al .…”

Section: Discussionmentioning

confidence: 99%

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Anti‐inflammatory and antiresorptive functions of melatonin on experimentally induced periapical lesions

Sarıtekin¹,

Kaya²,

Aşçı³

et al. 2019

Int Endodontic J

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“…While the majority of studies reported osteogenic effects of metformin in vitro [4–9, 40], there are reports indicating that metformin has no osteogenic effect [10] or inhibits osteoblast differentiation [11]. Metformin was also shown to inhibit osteoclast differentiation in vivo and in vitro by stimulating osteoprotegerin and inhibiting RANKL expressions [13, 41], although Bak et al [40] showed no effect of metformin on osteoclast formation. Few clinical studies in diabetic patients have assessed the effect of metformin as a monotherapy on fracture risk, and they show overall poor evidence that it has major anabolic effects on bone.…”

Section: Discussionmentioning

confidence: 99%

The anti-diabetic drug metformin does not affect bone mass in vivo or fracture healing

et al. 2013

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SummaryThe present study shows no adverse effects of the anti-diabetic drug metformin on bone mass and fracture healing in rodents but demonstrates that metformin is not osteogenic in vivo, as previously proposed.IntroductionIn view of the increased incidence of fractures in patients with type 2 diabetes mellitus (T2DM), we investigated the effects of metformin, a widely used T2DM therapy, on bone mass and fracture healing in vivo using two different rodent models and modes of metformin administration.MethodsWe first subjected 12-week-old female C57BL/6 mice to ovariectomy (OVX). Four weeks after OVX, mice received either saline or metformin administered by gavage (100 mg/kg/daily). After 4 weeks of treatment, bone micro-architecture and cellular activity were determined in tibia by micro-CT and bone histomorphometry. In another experiment, female Wistar rats aged 3 months were given only water or metformin for 8 weeks via the drinking water (2 mg/ml). After 4 weeks of treatment, a mid-diaphyseal osteotomy was performed in the left femur. Rats were sacrificed 4 weeks after osteotomy and bone architecture analysed by micro-CT in the right tibia while fracture healing and callus volume were determined in the left femur by X-ray analysis and micro-CT, respectively.ResultsIn both models, our results show no significant differences in cortical and trabecular bone architecture in metformin-treated rodents compared to saline. Metformin had no effect on bone resorption but reduced bone formation rate in trabecular bone. Mean X-ray scores assessed on control and metformin fractures showed no significant differences of healing between the groups. Fracture callus volume and mineral content after 4 weeks were similar in both groups.ConclusionsOur results indicate that metformin has no effect on bone mass in vivo or fracture healing in rodents.

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“…Other studies reported the ability of metformin to prevent antiosteogenic effect of rosiglitazone in rats (28), to reduce receptor activator of nuclear factor κB ligand (RANKL) as well as to stimulate osteoprotegerin (OPG) expression in osteoblasts (7) RAT GROUP and to inhibit the periapical lesions in rats possibly by lowering the RANKL/ OPG ratio, subsequently reducing the number of osteoclasts and bone resorption areas (29). Indeed, another study reported that local delivery of metformin into periodontal pocket stimulated periodontal healing in chronic periodontitis patients (30).…”

Section: Discussionmentioning

confidence: 99%

Metformin as a Potential Therapeutic Agent for Osteoporosis in Ovariectomized Rats

Baraka¹

2014

Acta Endo (Buc)

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Introduction.There is increasing evidence that 5' adenosine monophosphateactivated protein kinase (AMPK) signaling pathway plays a role in bone physiology. The aim of the present study was to investigate the effect of a drug activating AMPK, namely metformin, on ovariectomy-induced osteoporosis in the rat.Methods. The present study was conducted on 40 female Wistar albino rats that were divided into 4 groups of 10 rats each, Group I: sham operated, Group II: non-treated ovarictomized (OVX) rats, while groups III and IV were OVX rats treated with metformin and metformin plus a substance that inhibits AMPK, namely compound C, respectively. At the end of the experimental period, urine and blood samples were collected and used for determination of urinary deoxypyridinoline (DPD) serum: osteocalcin, calcium and phosphorus concentrations and serum alkaline phosphatase activity. Biochemical assessment of AMPK activity in isolated fourth lumbar vertebrae (LV4) was carried out. The tibia, left femur and third lumbar vertebrae (LV3) were weighed and biomechanical study on LV3 was carried out. Immune histochemical studies of right femur and the forth-lumbar vertebrae (LV4) were carried out using anti-Fas antibodies to detect apoptotic osteoclastic and osteoblastic cells. Evaluation of cortical bone morphometric indices was done by CT-Scanning technique.Results. The results of the present study demonstrated that metfromin protected against biochemical, histological, biomechanical and histomorphometric osteoporotic changes. Compound C, an inhibitor of AMPK, blocked metformininduced changes in assessed parameters suggesting that the effect of metformin was mediated mainly through activation of AMPK.Conclusions. Drugs modulating AMPK could be effective in ameliorating OVX-induced osteoporotic changes.

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Protective Effect of Metformin on Periapical Lesions in Rats by Decreasing the Ratio of Receptor Activator of Nuclear Factor Kappa B Ligand/Osteoprotegerin

Cited by 72 publications

References 32 publications

Anti‐inflammatory and antiresorptive functions of melatonin on experimentally induced periapical lesions

Anti‐inflammatory and antiresorptive functions of melatonin on experimentally induced periapical lesions

The anti-diabetic drug metformin does not affect bone mass in vivo or fracture healing

Metformin as a Potential Therapeutic Agent for Osteoporosis in Ovariectomized Rats

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