Epigallocatechin-3-gallate inhibits osteoclastic differentiation by modulating mitophagy and mitochondrial functions

Sarkar, Jaganmay; Das, Manjusri; Howlader, Md Sariful Islam; Prateeksha, Prateeksha; Barthels, Derek; Das, Hiranmoy

doi:10.1038/s41419-022-05343-1

Cited by 31 publications

(15 citation statements)

References 57 publications

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“…Mitochondrial dysfunction is directly linked with pathogenesis in several disease conditions [ 27 , 35 – 38 ] ; therefore, we wanted to evaluate the effect of DPSC ℗ on the MMP in U-87 MG cells using JC1 staining. JC1 accumulates in polarized mitochondria and emits red fluorescence, while JC1 remains in monomer form in depolarized mitochondria and emits green fluorescence.…”

Section: Resultsmentioning

confidence: 99%

Secretome of Dental Pulp-Derived Stem Cells Reduces Inflammation and Proliferation of Glioblastoma Cells by Deactivating Mapk-Akt Pathway

Prateeksha¹,

Howlader²,

Hansda³

et al. 2023

jbyyj

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Background: Dental pulp-derived stem cells (DPSC) is a promising therapy as they modulate the immune response, so we evaluated the inhibitory effect of DPSC secretome (DPSC ℗ ) on the proliferation and inflammation in human glioblastoma (GBM) cells (U-87 MG) and elucidated the concomitant mechanisms involved. Methods: The U87-MG cells were cultured with DPSC ℗ for 24 h and assessed the expression of inflammatory molecules using quantitative reverse transcription-polymerase chain reaction (qRT-PCR), generation of reactive oxygen species (ROS), and mitochondrial functionality using a seahorse flux analyzer. MTT (3-(4, 5-dimethylthiazolyl-2)-2, 5-diphenyltetrazolium bromide) assay and cell cycle analysis were performed to evaluate the proliferation and cell cycle. Finally, the protein levels were determined by western blot. Results: DPSC ℗ reduced the inflammation and proliferation of U-87 MG cells by down-regulating the pro-inflammatory markers and up-regulating anti-inflammatory markers expressions through ROS-mediated signaling. Moreover, DPSC ℗ significantly reduced the mitochondrial membrane potential (MMP) in the cells. The cellular bioenergetics revealed that all the parameters of oxygen consumption rate (OCAR) and the extracellular acidification rate (ECAR) were significantly decreased in the GBM cells after the addition of DPSC ℗ . Additionally, DPSC ℗ decreased the GBM cell proliferation by arresting the cell cycle at the G1 phase through activation (phosphorylation) of checkpoint molecule CHK1. Furthermore, mechanistically, we found that the DPSC ℗ impedes the phosphorylation of the mitogen-activated protein kinases (P38 MAPK) and protein kinase B (AKT) pathway. Conclusion: Our findings lend the first evidence of the inhibitory effects of DPSC ℗ on proliferation and inflammation in GBM cells by altering the P38 MAPK-AKT pathway.

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Section: Resultsmentioning

confidence: 99%

Secretome of Dental Pulp-Derived Stem Cells Reduces Inflammation and Proliferation of Glioblastoma Cells by Deactivating Mapk-Akt Pathway

Prateeksha¹,

Howlader²,

Hansda³

et al. 2023

jbyyj

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“…Chen ( 73 ) found that vitamin K2 can promote the expression of LC3-II, PINK1 and Parkin proteins to enhance mitophagy in osteoblast, thus playing an anti-osteoporosis role. Studies have found that epigallocatechin-3-gallate (EGCG) is a rich polyphenol in green tea, which can reduce the production of intracellular and mitochondrial ROS, increase the production of ATP, significantly reduce the mitochondrial membrane potential and the expression of mitochondrial autophagy related molecules PINK1 and Parkin, reduce mitophagy, and inhibit osteoclast differentiation ( 74 ). These findings indicate that many mitophagy enhancers have been proved to promote osteoblast differentiation, while in osteoclasts, mitophagy inhibitors can treat osteoporosis by inhibiting its differentiation.…”

Section: Potential Therapeutic Targeting Of Mitochondria In Osteoporosismentioning

confidence: 99%

Mitochondrial quality control and its role in osteoporosis

et al. 2023

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Mitochondria are important organelles that provide cellular energy and play a vital role in cell differentiation and apoptosis. Osteoporosis is a chronic metabolic bone disease mainly caused by an imbalance in osteoblast and osteoclast activity. Under physiological conditions, mitochondria regulate the balance between osteogenesis and osteoclast activity and maintain bone homeostasis. Under pathological conditions, mitochondrial dysfunction alters this balance; this disruption is important in the pathogenesis of osteoporosis. Because of the role of mitochondrial dysfunction in osteoporosis, mitochondrial function can be targeted therapeutically in osteoporosis-related diseases. This article reviews different aspects of the pathological mechanism of mitochondrial dysfunction in osteoporosis, including mitochondrial fusion and fission, mitochondrial biogenesis, and mitophagy, and highlights targeted therapy of mitochondria in osteoporosis (diabetes induced osteoporosis and postmenopausal osteoporosis) to provide novel targets and prevention strategies for the prevention and treatment of osteoporosis and other chronic bone diseases.

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“…The expression of functional proteins corresponding to osteoclasts and nuclear factor activated T‐cells 1 (NFATc1) is strongly influenced by these pathways (Bae et al, 2023; Ibáñez et al, 2022). NFATc1, as a significant regulator of osteoclast differentiation, automatically expands and regulates the expression of numerous osteoclast‐related proteins, including cathepsin K (CTSK), dendritic cell‐specific transmembrane protein (DC‐STAMP), tartrate‐resistant acid phosphatase, and ATPase H + transporting V0 subunit D2 (ATP6V0D2) (Bae et al, 2023; Hu et al, 2021; Ibáñez et al, 2022; Sarkar et al, 2022).…”

Section: Introductionmentioning

confidence: 99%

Cichoric acid targets RANKL to inhibit osteoclastogenesis and prevent ovariectomy‐induced bone loss

Xian,

Gao,

et al. 2024

Phytotherapy Research

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Background and AimOsteoporosis, a systemic metabolic bone disease, is characterized by the decline of bone mass and quality due to excessive osteoclast activity. Currently, drug‐targeting osteoclasts show promising therapy for osteoporosis. In this study, we investigated the effect of cichoric acid (CA) on receptor activator of nuclear kappa‐B ligand (RANKL)‐induced osteoclastogenesis and the bone loss induced by ovariectomy in mice.Experimental ProcedureMolecular docking technologies were employed to examine the interaction between CA and RANKL. CCK8 assay was used to evaluate the cell viability under CA treatment. TRAcP staining, podosome belt staining, and bone resorption assays were used to test the effect of CA on osteoclastogenesis and osteoclast function. Further, an OVX‐induced osteoporosis mice model was employed to identify the effect of CA on bone loss using micro‐CT scanning and histological examination. To investigate underlying mechanisms, network pharmacology was applied to predict the downstream signaling pathways, which were verified by Western blot and immunofluorescence staining.Key ResultsThe molecular docking analysis revealed that CA exhibited a specific binding affinity to RANKL, engaging multiple binding sites. CA inhibited RANKL‐induced osteoclastogenesis and bone resorption without cytotoxic effects. Mechanistically, CA suppressed RANKL‐induced intracellular reactive oxygen species, nuclear factor‐kappa B, and mitogen‐activated protein kinase pathways, followed by abrogated nuclear factor activated T‐cells 1 activity. Consistent with this finding, CA attenuated post‐ovariectomy‐induced osteoporosis by ameliorating osteoclastogenesis.Conclusions and ImplicationsCA inhibited osteoclast activity and bone loss by targeting RANKL. CA might represent a promising candidate for treating osteoclast‐related diseases, such as osteoporosis.

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Epigallocatechin-3-gallate inhibits osteoclastic differentiation by modulating mitophagy and mitochondrial functions

Cited by 31 publications

References 57 publications

Secretome of Dental Pulp-Derived Stem Cells Reduces Inflammation and Proliferation of Glioblastoma Cells by Deactivating Mapk-Akt Pathway

Secretome of Dental Pulp-Derived Stem Cells Reduces Inflammation and Proliferation of Glioblastoma Cells by Deactivating Mapk-Akt Pathway

Mitochondrial quality control and its role in osteoporosis

Cichoric acid targets RANKL to inhibit osteoclastogenesis and prevent ovariectomy‐induced bone loss

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