Novel antioxidative nanotherapeutics in a rat periodontitis model: Reactive oxygen species scavenging by redox injectable gel suppresses alveolar bone resorption

Saita, Makiko; Kaneko, Junya; Sato, Takenori; Takahashi, Shunsuke; Wada-Takahashi, Satoko; Kawamata, Ryota; Sakurai, Takashi; Lee, Masaichi-Chang-il; Hamada, Naoki; Kimoto, Katsuhiko; Nagasaki, Yukio

doi:10.1016/j.biomaterials.2015.10.077

Cited by 81 publications

(69 citation statements)

References 38 publications

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“…), which is in sharp contrast to Exe@nRIG, Exe&TEMPO@nRIG, Exe (once weekly), and PBS, which caused degenerated pancreatic islets and loss of islet volume. We have already confirmed that the elimination of excess ROS suppressed adverse events such as inflammation related to ROS‐induced oxidative stress . In addition, it has been reported that db / db mice treated with an antioxidant preserved the pancreatic islet architecture .…”

Section: Discussionsupporting

confidence: 72%

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Redox‐active injectable gel using polyion complex to achieve sustained release of exenatide and enhance therapeutic efficacy for the treatment of type 2 diabetes

Shiro

Sakaue

Nagasaki

2019

J Biomedical Materials Res

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To provide sustained release of exenatide and enhance therapeutic efficacy for the treatment of type 2 diabetes compared to the existing products for exenatide, we developed an exenatide‐loaded, redox‐active, injectable gel (Exe@RIG). This injectable gel is formed by a polyion complex (PIC) comprising three components, (1) cationic polyamine–poly(ethylene glycol)–polyamine triblock copolymer possessing reactive oxygen species (ROS)‐scavenging moieties as side chains, (2) anionic poly(acrylic acid), and (3) exenatide. The mixture formed exenatide‐loaded PIC flower micelles at room temperature, which immediately converted to a gel under physiological conditions. Owing to electrostatic interactions between exenatide and the PIC gel network, RIG was able to provide sustained release of exenatide without a significant initial burst. Subcutaneous injection of Exe@RIG once a week prevented the increase in glucose concentration significantly in db/db mice compared to those in control groups. In addition, Exe@RIG suppressed the degeneration of pancreatic islets, which is reported to be caused by increased ROS. Our result indicates that Exe@RIG has the potential to provide a long acting exenatide as well as enhanced efficacy in the treatment of type 2 diabetes compared to the existing products. © 2019 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 107A: 1107–1113, 2019.

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Section: Discussionsupporting

confidence: 72%

“…In addition, PMNT–PEG–PMNT possesses ROS‐scavenging moieties as side chains. RIG can therefore suppress adverse events such as ROS‐induced oxidative stress …”

Section: Introductionmentioning

confidence: 99%

Redox‐active injectable gel using polyion complex to achieve sustained release of exenatide and enhance therapeutic efficacy for the treatment of type 2 diabetes

Shiro

Sakaue

Nagasaki

2019

J Biomedical Materials Res

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“…Over-production of ROS may reduce cellular glutathione, damage DNA, proteins and lipids, to activate check-point kinases and control the cell cycle- and apoptosis-related genes [39,40]. Lately redox injectable gel has been effectively used to scavenge ROS and suppresses alveolar bone resorption in rat periodontitis models [41], suggesting the role of ROS in periodontal/periapical bony destruction. Intriguingly, ROS levels in MG-63 cell are elevated after exposure to butyrate in this study.…”

Section: Discussionmentioning

confidence: 99%

Effect of Butyrate on Collagen Expression, Cell Viability, Cell Cycle Progression and Related Proteins Expression of MG-63 Osteoblastic Cells

et al. 2016

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AimsButyric acid is one major metabolic product generated by anaerobic Gram-negative bacteria of periodontal and root canal infection. Butyric acid affects the activity of periodontal cells such as osteoblasts. The purposes of this study were to investigate the effects of butyrate on MG-63 osteoblasts.MethodsMG-63 cells were exposed to butyrate and cell viability was estimated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The mRNA and protein expression of type I collagen and cell cycle-related proteins were measured by reverse-transcriptase polymerase chain reaction (RT-PCR), western blotting or immunofluorescent staining. Cellular production of reactive oxygen species (ROS) was analyzed by 2',7'-dichlorofluorescein (DCF) fluorescence flow cytometry.ResultsExposure to butyrate suppressed cell proliferation, and induced G2/M (8 and 16 mM) cell cycle arrest of MG-63 cells. Some cell apoptosis was noted. The mRNA expression of cdc2 and cyclin-B1 decreased after exposure to butyrate. The protein expression of type I collagen, cdc2 and cyclin B1 were decreased, whereas the expression of p21, p27 and p57 was stimulated. Under the treatment of butyrate, ROS production in MG-63 cells markedly increased.ConclusionsThe secretion of butyric acid by periodontal and root canal microorganisms may inhibit bone cell growth and matrix turnover. This is possibly due to induction of cell cycle arrest and ROS generation and inhibition of collagen expression. These results suggest the involvement of butyric acid in the pathogenesis of periodontal and periapical tissue destruction by impairing bone healing responses.

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“…At low concentrations, ROS stimulate the proliferation and differentiation of human periodontal ligament fibroblasts (hPDLFs) in culture, while at higher concentrations, they may have cytotoxic effects on periodontal tissues and participate in pathogen killing (Chapple and Matthews, 2007; D'aiuto et al, 2010; Galli et al, 2011; Saita et al, 2016). …”

Section: Ros In Periodontitismentioning

confidence: 99%

The Role of Reactive Oxygen Species and Autophagy in Periodontitis and Their Potential Linkage

et al. 2017

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Periodontitis is a chronic inflammatory disease that causes damage to periodontal tissues, which include the gingiva, periodontal ligament, and alveolar bone. The major cause of periodontal tissue destruction is an inappropriate host response to microorganisms and their products. Specifically, a homeostatic imbalance between reactive oxygen species (ROS) and antioxidant defense systems has been implicated in the pathogenesis of periodontitis. Elevated levels of ROS acting as intracellular signal transducers result in autophagy, which plays a dual role in periodontitis by promoting cell death or blocking apoptosis in infected cells. Autophagy can also regulate ROS generation and scavenging. Investigations are ongoing to elucidate the crosstalk mechanisms between ROS and autophagy. Here, we review the physiological and pathological roles of ROS and autophagy in periodontal tissues. The redox-sensitive pathways related to autophagy, such as mTORC1, Beclin 1, and the Atg12-Atg5 complex, are explored in depth to provide a comprehensive overview of the crosstalk between ROS and autophagy. Based on the current evidence, we suggest that a potential linkage between ROS and autophagy is involved in the pathogenesis of periodontitis.

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Novel antioxidative nanotherapeutics in a rat periodontitis model: Reactive oxygen species scavenging by redox injectable gel suppresses alveolar bone resorption

Cited by 81 publications

References 38 publications

Redox‐active injectable gel using polyion complex to achieve sustained release of exenatide and enhance therapeutic efficacy for the treatment of type 2 diabetes

Redox‐active injectable gel using polyion complex to achieve sustained release of exenatide and enhance therapeutic efficacy for the treatment of type 2 diabetes

Effect of Butyrate on Collagen Expression, Cell Viability, Cell Cycle Progression and Related Proteins Expression of MG-63 Osteoblastic Cells

The Role of Reactive Oxygen Species and Autophagy in Periodontitis and Their Potential Linkage

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