GSH attenuates RANKL-induced osteoclast formation in vitro and LPS-induced bone loss in vivo

Han, Bing; Geng, Hui-Xia; Lv, Liang; Wu, Zhixin; Wang, Yizhong

doi:10.1016/j.biopha.2020.110305

Cited by 22 publications

(27 citation statements)

References 28 publications

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“…Literature mining shows that RANKL induced osteoclastogenesis is augmented by depletion of B 6 or B 12 in media. Knock down of CBS which came up as a critical gene in three of the four data set in our integrated analysis increased osteoclastogenesis, while supplementation of glutathione was shown to inhibit osteoclastogenesis 68 . CBS KO mice showed increased osteoclastogenesis and osteoporosis which could be mitigated by supplementation of N-acetyl cysteine.…”

Section: Discussionmentioning

confidence: 81%

Systems analysis of avascular necrosis of femoral head using integrative data analysis and literature mining delineates pathways associated with disease

Naik

Narayanan

Khanchandani

et al. 2020

Sci Rep

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Avascular necrosis of femoral head (AVNFH) is a debilitating disease, which affects the middle aged population. Though the disease is managed using bisphosphonate, it eventually leads to total hip replacement due to collapse of femoral head. Studies regarding the association of single nucleotide polymorphisms with AVNFH, transcriptomics, proteomics, metabolomics, biophysical, ultrastructural and histopathology have been carried out. Functional validation of SNPs was carried out using literature. An integrated systems analysis using the available datasets might help to gain further insights into the disease process. We have carried out an analysis of transcriptomic data from GEO-database, SNPs associated with AVNFH, proteomic and metabolomic data collected from literature. Based on deficiency of vitamins in AVNFH, an enzyme-cofactor network was generated. The datasets are analyzed using ClueGO and the genes are binned into pathways. Metabolomic datasets are analyzed using MetaboAnalyst. Centrality analysis using CytoNCA on the data sets showed cystathionine beta synthase and methylmalonyl-CoA-mutase to be common to 3 out of 4 datasets. Further, the genes common to at least two data sets were analyzed using DisGeNET, which showed their involvement with various diseases, most of which were risk factors associated with AVNFH. Our analysis shows elevated homocysteine, hypoxia, coagulation, Osteoclast differentiation and endochondral ossification as the major pathways associated with disease which correlated with histopathology, IHC, MRI, Micro-Raman spectroscopy etc. The analysis shows AVNFH to be a multi-systemic disease and provides molecular signatures that are characteristic to the disease process.

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Section: Discussionmentioning

confidence: 81%

Systems analysis of avascular necrosis of femoral head using integrative data analysis and literature mining delineates pathways associated with disease

Naik

Narayanan

Khanchandani

et al. 2020

Sci Rep

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“…NAC treatment enhanced ALP activity in the process of osteogenic differentiation, which was related to the increased GSH/GSSG ratio in NAC-treated cells [38]. GSH suppressed RANKL-induced osteoclastogenesis by inhibiting intracellular ROS generation [39]. Our results presented that NAC supplement inhibited the elevation of ROS production and enhanced the level of GSH and the ratio of GSH/GSSG in PDLSCs, suggesting that NAC application improved antioxidant capacity through decreased ROS production and the increased ratio of GSH/GSSG, which might contribute to the promotion of osteogenic differentiation in PDLSCs under cyclic mechanical stretch.…”

Section: Discussionmentioning

confidence: 90%

N-acetylcysteine promotes osteogenic differentiation in periodontal ligament stem cells under cyclic mechanical stretch

Zhao

et al. 2021

Preprint

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Background Biomechanical forces are vital for the regulation of skeletal tissue. Mechanical stretch plays a vital role in osteogenic differentiation of periodontal ligament stem cells (PDLSCs) during orthodontic treatment. Cyclic mechanical stretch may trigger the up-regulated production of reactive oxygen species (ROS). ROS has a critical effect on bone cell function and the pathophysiology of bone diseases. N-acetylcysteine (NAC), a ROS scavenger, possesses powerful antioxidant capacity. The aim of this study was to determine the role of ROS and NAC in PDLSCs during osteogenic differentiation under cyclic mechanical stretch. We further investigated that the therapeutic potential of NAC to improve the changes of the microstructure of alveolar bone during orthodontic tooth movement in rats by micro-CT system. Methods The expression of COL1 (collagen type I), RUNX2 (runt-related transcription factor 2) and OPN (osteopontin) by qRT-PCR and Western blot experiments, and alkaline phosphatase (ALP) staining as well as ALP activity tests were used to examine osteogenic differentiation tendency of PDLSCs subjected to cyclic mechanical stretch of 10% and 0.5Hz deformation induced by the Flexcell tension system. ROS production in PDLSCs were measured under cyclic mechanical stretch by Flow Cytometry. The levels of reduced glutathione (GSH), oxidized GSH (GSSG) and the GSH/GSSG ratio with or without NAC treatment were analyzed. And we evaluated the changes of the microstructure of alveolar bone during orthodontic tooth movement in rats employing micro-CT system. Results NAC treatment could promote the osteogenic differentiation of PDLSCs under cyclic mechanical stretch. Down-regulated ROS generation and the up-regulated level of GSH and the ratio of GSH/GSSG in PDLSCs treated with NAC were observed in response to cyclic mechanical stretch. NAC improved the microstructure of alveolar bone, including BV/TV (bone volume/total volume), Tb.Th (trabecular thickness), Tb.Sp (trabecular separation) and SMI (microstructure model index), during orthodontic tooth movement in rats. Conclusion These results revealed that NAC might be a potential therapeutic approach for the remodeling of the alveolar bone during orthodontic tooth movement.

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“…Previous reports on ROS production and RANKL-induced osteoclastogenesis have shown that ROS levels regulate expression and activity of differentiation factors during osteoclastogenesis, thereby determining the number of mature osteoclasts and bone density, but that ROS levels do not affect osteoblastogenesis (Kim et al, 2010, Kim J.H. et al, 2015Goettsch et al, 2013;Hyeon et al, 2013;Kang and Kim, 2016;Lee et al, 2019;Ng et al, 2019;Han et al, 2020). Lee et al (2019) has recently reported that reduction in osteoclast differentiation and increased bone density through regulation of ROS signaling result from reduced RANKL secretion by osteoblasts.…”

Section: Discussionmentioning

confidence: 99%

Sestrin2 Regulates Osteoclastogenesis via the p62-TRAF6 Interaction

Kang

et al. 2021

Front. Cell Dev. Biol.

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The receptor activator of nuclear factor-kappa B ligand (RANKL) mediates osteoclast differentiation and functions by inducing Ca2+ oscillations, activating mitogen-activated protein kinases (MAPKs), and activating nuclear factor of activated T-cells type c1 (NFATc1) via the RANK and tumor necrosis factor (TNF) receptor-associated factor 6 (TRAF6) interaction. Reactive oxygen species (ROS) also plays an important role during osteoclastogenesis and Sestrin2, an antioxidant, maintains cellular homeostasis upon stress injury via regulation of ROS, autophagy, and inflammation. However, the role of Sestrin2 in osteoclastogenesis remains unknown. In this study, we investigated the role of Sestrin2 in the RANKL-RANK-TRAF6 signaling pathway during osteoclast differentiation. Deletion of Sestrin2 (Sesn2) increased bone mass and reduced the number of multinucleated osteoclasts on bone surfaces. RANKL-induced osteoclast differentiation and function decreased in Sesn2 knockout (KO) bone marrow-derived monocytes/macrophages (BMMs) due to inhibition of NFATc1 expression, but osteoblastogenesis was not affected. mRNA expression of RANKL-induced specific osteoclastogenic genes and MAPK protein expression were lower in Sesn2 KO BMMs than wild-type (WT) BMMs after RANKL treatment. However, the Sesn2 deletion did not affect ROS generation or intracellular Ca2+ oscillations during osteoclastogenesis. In contrast, the interaction between TRAF6 and p62 was reduced during osteoclasts differentiation in Sesn2 KO BMMs. The reduction in the TRAF6/p62 interaction and TRAP activity in osteoclastogenesis in Sesn2 KO BMMs was recovered to the WT level upon expression of Flag-Sesn2 in Sesn2 KO BMMs. These results suggest that Sestrin2 has a novel role in bone homeostasis and osteoclasts differentiation through regulation of NFATc1 and the TRAF6/p62 interaction.

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GSH attenuates RANKL-induced osteoclast formation in vitro and LPS-induced bone loss in vivo

Cited by 22 publications

References 28 publications

Systems analysis of avascular necrosis of femoral head using integrative data analysis and literature mining delineates pathways associated with disease

Systems analysis of avascular necrosis of femoral head using integrative data analysis and literature mining delineates pathways associated with disease

N-acetylcysteine promotes osteogenic differentiation in periodontal ligament stem cells under cyclic mechanical stretch

Sestrin2 Regulates Osteoclastogenesis via the p62-TRAF6 Interaction

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