Dataset Information

FoxO1 Overexpression Ameliorates TNF-?-Induced Oxidative Damage and Promotes Osteogenesis of Human Periodontal Ligament Stem Cells via Antioxidant Defense Activation.

ABSTRACT: Periodontitis is a chronic disease that includes the pathologic loss of periodontal tissue and alveolar bone. The inflammatory environment in periodontitis impairs the osteogenic differentiation potential and depresses the regeneration capacity of human periodontal ligament stem cells (hPDLSCs). Since Forkhead box protein O1 (FoxO1) plays an important role in redox balance and bone formation, we investigated the role of FoxO1 in oxidative stress resistance and osteogenic differentiation in an inflammatory environment by overexpressing FoxO1 in hPDLSCs. First, we found that FoxO1 overexpression reduced reactive oxygen species (ROS) accumulation, decreased malondialdehyde (MDA) levels, and elevated antioxidant potential under oxidative condition. Next, the overexpression of FoxO1 protected hPDLSCs against oxidative damage, which involved stabilization of the mitochondrial membrane potential. Third, overexpressed FoxO1 promoted extracellular matrix (ECM) mineralization and increased the expression of the osteogenic markers Runx2 and SP7 in the inflammatory environment. These results indicated that FoxO1 overexpression in hPDLSCs has an anti-inflammatory effect, increases antioxidative capacity, and positively regulates osteogenesis in a mimicked inflammatory environment.

SUBMITTER: Huang X

PROVIDER: S-EPMC6875375 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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FoxO1 Overexpression Ameliorates TNF-<i>α</i>-Induced Oxidative Damage and Promotes Osteogenesis of Human Periodontal Ligament Stem Cells via Antioxidant Defense Activation.

Huang Xiaojun X Chen Huan H Xie Yunyi Y Cao Zeyuan Z Lin Xuefeng X Wang Yan Y

Stem cells international 20191031

Periodontitis is a chronic disease that includes the pathologic loss of periodontal tissue and alveolar bone. The inflammatory environment in periodontitis impairs the osteogenic differentiation potential and depresses the regeneration capacity of human periodontal ligament stem cells (hPDLSCs). Since Forkhead box protein O1 (FoxO1) plays an important role in redox balance and bone formation, we investigated the role of FoxO1 in oxidative stress resistance and osteogenic differentiation in an in ...[more]

PMID: 31781234

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Project description:The dysfunction of mesangial cells (MCs) in high-glucose (HG) conditions plays pivotal role in inducing glomerular sclerosis by causing the imbalance between generation and degradation of extracellular matrix (ECM) proteins, which ultimately leads to diabetic nephropathy. This study was designed to determine the function of forkhead box protein O1 (FoxO1), an important transcription factors in regulating cell metabolism and oxidative stress, in MCs in HG conditions. Up-regulation of fibronectin, collagen type IV, and plasminogen activator inhibitor (PAI-1) was observed under HG conditions in vivo and in vitro, accompanied with elevation of protein kinase B (Akt) phosphorylation and reduction of FoxO1 bioactivity. After overexpression of constitutively active (CA) FoxO1 in vivo and in vitro by using lentivirus vector, in vivo and in vitro, FoxO1 expression and activity was increased, in accordance with up-regulation of antioxidative genes (catalase and superoxide dismutase, leading to alleviated oxidative stress as well as attenuated Akt activity, whereas overexpression of wild type-FoxO1 only expressed partial effect. Moreover, CA-FoxO1 decreased the expression of fibronectin, collagen type IV, and PAI-1, causing amelioration of renal pathological changes and decrease of ECM protein deposition in glomerulus. Overexpression of CA-FoxO1 in renal cortex also decreased activin type-I receptor-like kinase-5 levels and increased signaling mothers against decapentaplegic (Smad) 7 levels, and simultaneously inhibited Smad3 phosphorylation. Results from in vitro study indicated that increased combination of FoxO1 and Smad3 may interfere with the function of Smad3, including Smad3 phosphorylation and translocation, interaction with cAMP response element binding protein (CREB)-binding protein, and binding with PAI-1 promoter. Together, our findings shed light on the novel function of FoxO1 in inhibiting ECM deposition, which is beneficial to ameliorate MC dysfunction.

Project description:The structural and functional integrity of bone-periodontal ligament (PDL)-cementum complex stems from the load-bearing attachment sites (entheses) between soft (PDL) and hard (bone, cementum) tissues. These attachment sites are responsible for the maintenance of a bone-PDL-cementum complex biomechanical function. The objective was to investigate changes in spatiotemporal expression of key biomolecules in developing and functionally active entheses.Multilabeling technique was performed on hemimandibles of 3 wk and 3 mo-old scleraxis-GFP transgenic mice for CD146, CD31, NG2, osterix and bone sialoprotein. Regions of dominant stretch within the PDL were evaluated by identifying directionality of collagen fibrils, PDL fibroblasts and PDL cell cytoskeleton.CD146+ cells adjacent to CD31+ vasculature were identified at PDL-bone enthesis. NG2+ cells were located at coronal bone-PDL and apical cementum-PDL entheses in the 3-wk-old group, but at 3 mo, NG2 was positive at the entheses of the apical region and alveolar crest. NG2 and osterix were colocalized at the osteoid and cementoid regions of the PDL-bone and PDL-cementum entheses. Bone sialoprotein was prominent at the apical region of 3-wk-old mice. The directionality of collagen fibers, fibroblasts and their cytoskeleton overlapped, except in the apical region of 3 wk.Colocalization of biomolecules at zones of the PDL adjacent to attachment sites may be essential for the formation of precementum and osteoid interfaces at a load-bearing bone-PDL-tooth fibrous joint. Biophysical cues resulting from development and function can regulate recruitment and differentiation of stem cells potentially from a vascular origin toward osteo- and cemento-blastic lineages at the PDL-bone and PDL-cementum entheses. Investigating the coupled effect of biophysical and biochemical stimuli leading to cell differentiation at the functional attachment sites is critical for developing regeneration strategies to enable functional reconstruction of the periodontal complex.

Dataset Information

FoxO1 Overexpression Ameliorates TNF-?-Induced Oxidative Damage and Promotes Osteogenesis of Human Periodontal Ligament Stem Cells via Antioxidant Defense Activation.

Publications

FoxO1 Overexpression Ameliorates TNF-<i>α</i>-Induced Oxidative Damage and Promotes Osteogenesis of Human Periodontal Ligament Stem Cells via Antioxidant Defense Activation.

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