Metformin Ameliorates Periapical Lesions through Suppression of Hypoxia-induced Apoptosis of Osteoblasts

Lai, Eddie Hsiang-Hua; Yang, Cheng-Ning; Lin, Sze‐Kwan; Wang, Hanwei; Kok, Sang‐Heng; Hong, Chuang‐Ye; Su, I‐Hsuan; Yang, Hui‐Fang; Chang, Jenny Zwei-Chieng

doi:10.1016/j.joen.2018.08.002

Cited by 25 publications

(17 citation statements)

References 29 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This is consistent with previous studies reporting that metformin protects nucleus pulposus cells from apoptosis . The anti‐apoptosis effect of metformin was reported to be partially a result of its antioxidative activity . These results indicate that metformin may help cells to resist apoptosis, and that metformin can be used to improve tHA biocompatibility.…”

Section: Discussionsupporting

confidence: 92%

Effect of metformin on human periodontal ligament stem cells cultured with polydopamine‐templated hydroxyapatite

Zhan

Gao

Zhou

et al. 2019

European J Oral Sciences

View full text Add to dashboard Cite

Polydopamine‐templated hydroxyapatite (tHA) is a type of nano‐biomaterial that can promote osteogenesis in bone tissue engineering. However, high concentrations of tHA stimulate production of reactive oxygen species (ROS), resulting in cell injury and apoptosis. Metformin has been demonstrated to activate the adenosine monophosphate‐activated protein kinase (AMPK) signaling pathway, which induces autophagy and decreases ROS production to prevent apoptosis. The present study was performed to investigate the potential application of tHA in combination with metformin in periodontal bone tissue engineering. Human periodontal ligament stem cells (hPDLSCs) were exposed to tHA in the presence or absence of metformin, and cytocompatibility and osteogenesis were detected by related assays. Additionally, the autophagy signaling pathway was analyzed by western blotting. Polydopamine‐templated hydroxyapatite, in combination with metformin, substantially reduced ROS production and apoptosis, and enhanced proliferation and osteogenic differentiation of hPDLSCs. Enhanced levels of microtubule‐associated protein 1 light chain 3 II and Beclin‐1 were observed after exposure to tHA plus metformin. Expression of phosphorylated AMPK was increased and that of phosphorylated mammalian target of rapamycin (mTOR) was decreased after exposure to tHA plus metformin. Taken together, our results demonstrate that tHA, combined with metformin, increases the viability of hPDLSCs via the AMPK/mTOR signaling pathway by regulating autophagy and further improving the osteogenic effect.

show abstract

Section: Discussionsupporting

confidence: 92%

Effect of metformin on human periodontal ligament stem cells cultured with polydopamine‐templated hydroxyapatite

Zhan

Gao

Zhou

et al. 2019

European J Oral Sciences

View full text Add to dashboard Cite

show abstract

“…Grx5 silencing resulted in apoptosis when exposed to H 2 O 2 , whereas overexpression of Grx5 in osteoblasts prevents ROS cell apoptosis (Linares et al, 2009). Similarly, the mitochondrial targeted drug, metformin, has been shown to reduce the hypoxic‐induced oxidative stress and osteoblast apoptosis through suppression of cytochrome c release and cleavage of procaspase‐9 and poly(ADP‐ribose) polymerase (Lai et al, 2018). Oxidative stress may mediate osteoblast apoptosis through Wnt/B‐catenin signalling (Manolagas & Almeida, 2007).…”

Section: Reactive Oxygen Species (Ros) and Bonementioning

confidence: 99%

“Take My Bone Away?” Hypoxia and bone: A narrative review

Hannah

McFadden

McNeilly

et al. 2020

Journal Cellular Physiology

View full text Add to dashboard Cite

To maintain normal cellular and physiological function, sufficient oxygen is required. Recently, evidence has suggested that hypoxia, either pathological or environmental, may influence bone health. It appears that bone cells are distinctly responsive to hypoxic stimuli; for better or worse, this is still yet to be elucidated. Hypoxia has been shown to offer potentially therapeutic effects for bone by inducing an osteogenic-angiogenic response, although, others have noted excessive osteoclastic bone resorption instead. Much evidence suggests that the hypoxic-inducible pathway is integral in mediating the changes in bone metabolism. Furthermore, many factors associated with hypoxia including changes in energy metabolism, acid-base balance and the increased generation of reactive oxygen species, are known to influence bone metabolism. This review aims to examine some of the putative mechanisms responsible for hypoxic-induced alterations of bone metabolism, with regard to osteoclasts and osteoblasts, both positive and negative.

show abstract

“…In addition to this, antiproliferative and antiapoptotic properties of metformin, which we used as a positive control in our study, were indicated in various studies (Jia et al, 2015;Lai et al, 2018). It is known today that ROS and oxidative stress emerging as a result of ROS play a significant role in apoptosis, while antioxidants can delay or prevent this process (Kannan and Jain, 2004).…”

Section: Discussionmentioning

confidence: 80%

The effects of feeding obese rats with bee bread on leptin and ghrelin expression

Doğanyiğit¹,

Yakan²,

Soylu³

et al. 2020

Turk J Zool

View full text Add to dashboard Cite

Obesity is an important public health problem and a risk factor for many chronic diseases, and its prevalence is increasing rapidly. In recent years there has been interest in the impact of nutrients on obesity and this has been addressed as a research topic. Bee bread is a bee product that has recently attracted attention with its macro-and micronutrients and the enzymes and biocomponents it contains. Although there are many studies on the biological properties and effects of bee bread, its effect on obesity with leptin and ghrelin has not been investigated. In this study, 40 Sprague-Dawley adult female rats were separated into 4 groups after they had become obese by having been fed with commercial high-fat food. While the 1st group was the control, the 2nd group was the obese control and bee bread was given to the 3rd and 4th groups (100 and 200 mg/kg bw/day), and in the 5th group metformin (300 mg/kg/day) was provided. Histopathological and immunohistochemical analysis was performed in hypothalamus tissues, and biochemical analyses were conducted of blood samples and hypothalamus tissues by ELISA methods. The apoptotic cell level was determined by the TUNEL method. The results of the immunohistochemical assessment of the hypothalamus tissues were consistent, and the levels of leptin and ghrelin were inversely correlated in the samples. Biochemical analysis showed that MDA levels increased with obesity whereas differences in SOD, CAT, and XOD levels were not statistically significant. Bee bread improved lipid peroxidation caused by obesity. It was shown that obesity caused apoptotic cell count increase and bee bread decreased it. Bee bread administration (200 mg/kg/day) had positive effects on weight control and other parameters.

show abstract

Metformin Ameliorates Periapical Lesions through Suppression of Hypoxia-induced Apoptosis of Osteoblasts

Cited by 25 publications

References 29 publications

Effect of metformin on human periodontal ligament stem cells cultured with polydopamine‐templated hydroxyapatite

Effect of metformin on human periodontal ligament stem cells cultured with polydopamine‐templated hydroxyapatite

“Take My Bone Away?” Hypoxia and bone: A narrative review

The effects of feeding obese rats with bee bread on leptin and ghrelin expression

Contact Info

Product

Resources

About