Schisandrin C enhances odontoblastic differentiation through autophagy and mitochondrial biogenesis in human dental pulp cells

Takanche, Jyoti Shrestha; Kim, Jeong‐Seok; Kim, Jieun; Han, Shufen; Yi, Ho-Keun

doi:10.1016/j.archoralbio.2018.01.018

Cited by 16 publications

(13 citation statements)

References 33 publications

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“…Recently, it was demonstrated that resveratrol induced autophagy by directly inhibiting the mTOR-ULK1 pathway in human cells (Park et al, 2016). Moreover, previous studies have suggested that autophagy functions positively in odontoblastic differentiation (Takanche, Kim, Kim, Han, & Yi, 2018) and that autophagy maintains cellular homeostasis by improving pulpal mitochondrial activity (Y. H. Lee et al, 2015), while the present work further establishes a regulatory loop among resveratrol, autophagy, and the JNK signaling pathway in human DPSCs during TNFα-stimulated inflammatory responses.…”

Section: Discussionsupporting

confidence: 69%

Resveratrol represses tumor necrosis factor α/c-Jun N-terminal kinase signaling via autophagy in human dental pulp stem cells

Wang¹,

Hu²,

Liu³

et al. 2019

Archives of Oral Biology

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Objectives: To study the effects of polyphenol resveratrol on TNFα-induced inflammatory signaling as well as the underlying mechanism in human dental pulp stem cells (DPSCs). Materials and methods: Human DPSCs were cultured and treated by TNFα in the presence or absence of resveratrol. NF-κB and mitogen-activated protein kinase (MAPK) signaling pathways were analyzed by Western blotting and immunofluorescence staining. Interleukin 6 (IL6) and interleukin 8 (IL8) mRNA levels were analyzed by reverse transcription polymerase chain reaction. For the mechanistic study, autophagy was examined and further manipulated by gene silencing of Atg5 using siRNAs. Statistical analysis was performed by Student’s t-test, and values of p < 0.05 were considered significant. Results: Upon TNFα treatments, neither degradation of IκBα nor the phosphorylation and nuclear translocation of p65 NF-κB were inhibited by resveratrol at different concentrations. In contrast, resveratrol dramatically inhibited TNFα-induced phosphorylation of c-Jun N-terminal kinase (JNK) MAPK. Furthermore, resveratrol activated autophagy, as evidenced by the accumulated autophagic puncta formed by lipid bound LC3B in resveratrol-treated cells. Intriguingly, both resveratrol and JNK inhibitor SP600125 suppressed TNFα-induced IL6 and IL8 mRNA expression (P < 0.05). Silencing autophagy gene Atg5 led to the hyper-activation of JNK and augmented TNFα-induced IL6 and IL8 mRNA expression (P < 0.05). Conclusions: The results suggest that resveratrol suppresses TNFα-induced inflammatory cytokines expressed by DPSCs through regulating the inhibitory autophagy-JNK signaling cascade. Resveratrol might be beneficial to ameliorate pulpal damage during the acute phase of inflammation in vital pulp therapy.

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Section: Discussionsupporting

confidence: 69%

Resveratrol represses tumor necrosis factor α/c-Jun N-terminal kinase signaling via autophagy in human dental pulp stem cells

Wang¹,

Hu²,

Liu³

et al. 2019

Archives of Oral Biology

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“…The inducing effects of Schisandrin B on cell autophagy may contribute to its liver toxic effects [39]. Schisandrin C enhanced the regulation of autophagy to exert an anti-oxidative mechanism [40] or promote odontoblastic differentiation of human dental pulp cells [41]. For the conflicting roles of schisandrins on autophagy between different investigations, several reasons are considered, such as different cell types and drug treatment time.…”

Section: Discussionmentioning

confidence: 99%

Schizandrin Protects against OGD/R-Induced Neuronal Injury by Suppressing Autophagy: Involvement of the AMPK/mTOR Pathway

Wang

Zhang

et al. 2019

Molecules

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The neuroprotective role of schizandrin (SA) in cerebral ischemia-reperfusion (I/R) was recently highlighted. However, whether SA plays a regulatory role on autophagy in cerebral I/R injury is still unclear. This study aimed to explore whether the neuroprotective mechanisms of SA were linked to its regulation of AMP-activated protein kinase (AMPK)/mammalian target of rapamycin (mTOR)/autophagy pathway in vivo and in vitro. The present study confirmed that SA significantly improved oxygen-glucose deprivation/re-oxygenation (OGD/R)-induced PC12 cells injury. The results of immunoblotting and confocal microscope showed that SA decreased autophagy in OGD/R-injured PC12 cells, which was reflected by the decreased Beclin-1 and LC3-II expression, autophagy flux level, and LC3 puncta formation. In addition, the autophagy inducer rapamycin partially prevented the effects of SA on cell viability and autophagy after OGD/R, whereas the autophagy inhibitor 3-methyladenine (3-MA) exerted the opposite effect. The results of Western blotting showed that SA markedly decreased the phosphorylation of AMPK (p-AMPK), whereas the phosphor-mTOR (p-mTOR) levels increased in the presence of OGD/R insult. Furthermore, pretreatment with the AMPK inducer AICAR partially reversed the protective effects and autophagy inhibition of SA. However, AMPK inhibitor Compound C pretreatment further promoted the inhibition of SA on autophagy induction and cell damage induced by OGD/R. Taken together, these findings demonstrate that SA protects against OGD/R insult by inhibiting autophagy through the regulation of the AMPK-mTOR pathway and that SA may have therapeutic value for protecting neurons from cerebral ischemia.

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“…Mineral trioxide aggregate (MTA) inhibits autophagy via Notch pathway to enhance proliferation and odontoblastic differentiation of DPCs 67 . Schisandrin C activates autophagy in hDPCs to enhances its odontoblastic differentiation 68 . Furthermore, resin monomers 2‐hydroxyethyl methacrylate (HEMA) and triethylene glycol dimethacrylate (TEGDMA), two cytotoxic chemicals released from dental materials, activate autophagy in hDPSCs and dental mesenchymal cells, 69‐71 which are respectively mediated by nuclear factor‐kB (NF‐kB), MEK/ERK and AMPK/mTOR signal pathways 69‐71 .…”

Section: Physiological Functions Of Autophagy In Toothmentioning

confidence: 99%

“…Induction of autophagy by resveratrol suppresses the secretion of interleukin‐6 (IL‐6) and interleukin‐8 (IL8) by TNF‐a‐treated DPSCs 89 . Activation of autophagy by natural compound Schisandrin C enhances odontoblastic differentiation of hDPCs 68 …”

Section: Therapeutic Implication Of Autophagy In Toothmentioning

confidence: 99%

Autophagy in tooth: Physiology, disease and therapeutic implication

Yang

Fan²,

et al. 2021

Cell Biochemistry & Function

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Autophagy is an evolutionarily conserved cellular process, in which damaged organelles and proteins are engulfed in autophagic vesicles and subsequently fuse with lysosomes for degradation. Autophagy is widely involved in different physiologic or pathologic processes in human. Accumulating evidence indicates that autophagy operates as a critical quality control mechanism to maintain pulp homeostasis and structural integrity of the dentin‐pulp complex. Autophagy is activated during stresses and is involved in the pathogenesis of pulpitis and periapical infection. Recent discoveries have also provided intriguing insights into the roles of autophagy in tooth development, pulp aging and stress adaptation. In this review, we provide an update on the multifaceted functions of autophagy in physiology and pathophysiology of tooth. We also discuss the therapeutic implications of autophagy modulation in diseases and the regeneration of dentin‐pulp complex.

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Schisandrin C enhances odontoblastic differentiation through autophagy and mitochondrial biogenesis in human dental pulp cells

Cited by 16 publications

References 33 publications

Resveratrol represses tumor necrosis factor α/c-Jun N-terminal kinase signaling via autophagy in human dental pulp stem cells

Resveratrol represses tumor necrosis factor α/c-Jun N-terminal kinase signaling via autophagy in human dental pulp stem cells

Schizandrin Protects against OGD/R-Induced Neuronal Injury by Suppressing Autophagy: Involvement of the AMPK/mTOR Pathway

Autophagy in tooth: Physiology, disease and therapeutic implication

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