Nrf2 Activation Is Involved in Cyclic Mechanical Stress-Stimulated Osteogenic Differentiation in Periodontal Ligament Stem Cells via PI3K/Akt Signaling and HO1-SOD2 Interaction

Abstract

Nuclear factor erythroid-2-related factor-2 (Nrf2), the major transcriptional regulator in antioxidant response and cellular defense, had the vital effect on regulating osteogenic differentiation. Our previous study revealed that Nrf2 activation was involved in cyclic mechanical stress-stimulated osteogenic differentiation in the human periodontal ligament stem cells (PDLSCs). However, the mechanisms of Nrf2 underlying this process remained unclear. The goal of the study was to explore the mechanisms of Nrf2 in PDLSCs during cyclic mechanical stress-stimulated osteogenic differentiation via the tandem mass tag (TMT)-based liquid chromatography tandem-mass spectrometry (LC-MS/MS) analysis. And we applied tert-Butylhydroquinone (t-BHQ), the Nrf2 activator, to the orthodontic rats and detected the expression levels of the osteogenesis markers by immunohistochemistry (IHC) staining. Our results showed that Nrf2 activation in PDLSCs was involved in cyclic mechanical stress-stimulated osteogenic differentiation via phosphoinositide 3 kinase (PI3K)/protein kinase B (Akt) pathway. The protein-protein interaction between Akt and Nrf2 was detected. And the protein-protein interaction between heme oxygenase 1 (HO1) and superoxide dismutase 2 (SOD2), the downstream antioxidants of Nrf2, was associated with cyclic mechanical stress-stimulated osteogenic differentiation. T-BHQ enhanced the expression levels of the osteogenesis markers in orthodontic rats. Nrf2 might possess the potential to be a feasible molecular target in orthodontics.

Cellular communication network factor 1 interlinks autophagy and ERK signaling to promote osteogenesis of periodontal ligament stem cells

“…Our previous studies have demonstrated that the expression of osteogenic genes such as Runx2, Col 1, ALPL, OPN were upregulated after cyclic stretch loading, enhancing the mineralization formation of hPDLSCs 20,36 . In this study, we observed that the elevated expression of Runx2 and Col 1 were in concordance with CCN1 in response to stretch loading in vitro.…”

“…Our previous studies have demonstrated that the expression of osteogenic genes such as Runx2, Col 1, ALPL, OPN were upregulated after cyclic stretch loading, enhancing the mineralization formation of hPDLSCs. 20,36 In this study, we observed that the elevated expression of Runx2 and Col 1 were in concordance with CCN1 in response to stretch loading in vitro. CCN1 conditional knockout mice showed a significant lower bone mass in both trabecular and cortical bone and the blockade of CCN1 prevented bone fracture healing in mice.…”

Virus-Protein Corona Replacement Strategy to Improve the Antitumor Efficacy of Intravenously Injected Oncolytic Adenovirus

“…Proteomics assay of the virus protein corona was performed as previously reported with little modification. 37 Briefly, samples were divided into four groups (Bare ad11, Lip-ad11, ad11@SA, and PEG-Lipo) and each group contained three samples. The protein solution was added to a final concentration of 10 mM dithiothreitol (DTT), incubated for 1 h at 30 °C, and then returned to room temperature.…”

“…Proteomics assay of the virus protein corona was performed as previously reported with little modification . Briefly, samples were divided into four groups (Bare ad11, Lip-ad11, ad11@SA, and PEG-Lipo) and each group contained three samples.…”

The role of Nrf2 in periodontal disease by regulating lipid peroxidation, inflammation and apoptosis

“…Nrf2 activator T-BHQ promoted the osteogenic differentiation of PDLSCs under cyclic mechanical stretching, and enhanced the expression level of osteogenic markers in orthodontic rats. Micro-ct was used to observe that T-BHQ improved the microstructure of alveolar bone during orthodontic tooth movement in rats ( 108 , 109 ). Metformin can promote the osteogenic differentiation of PDLSCs by activating Akt/Nrf2 signaling pathway ( 110 ).…”