scholarly journals MicroRNA-29a Mitigates Osteoblast Senescence and Counteracts Bone Loss through Oxidation Resistance-1 Control of FoxO3 Methylation

Antioxidants ◽  
2021 ◽  
Vol 10 (8) ◽  
pp. 1248
Author(s):  
Wei-Shiung Lian ◽  
Re-Wen Wu ◽  
Yu-Shan Chen ◽  
Jih-Yang Ko ◽  
Shao-Yu Wang ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Bone Loss ◽  
Bone Mass ◽  
Oxidation Resistance ◽  
Dna Methyltransferase ◽  
Oxidative Stress Marker ◽  
Dna Hypermethylation ◽  
Bone Mass Loss ◽  
Old Mice

Senescent osteoblast overburden accelerates bone mass loss. Little is understood about microRNA control of oxidative stress and osteoblast senescence in osteoporosis. We revealed an association between microRNA-29a (miR-29a) loss, oxidative stress marker 8-hydroxydeoxyguanosine (8-OHdG), DNA hypermethylation marker 5-methylcystosine (5mC), and osteoblast senescence in human osteoporosis. miR-29a knockout mice showed low bone mass, sparse trabecular microstructure, and osteoblast senescence. miR-29a deletion exacerbated bone loss in old mice. Old miR-29a transgenic mice showed fewer osteoporosis signs, less 5mC, and less 8-OHdG formation than age-matched wild-type mice. miR-29a overexpression reversed age-induced senescence and osteogenesis loss in bone-marrow stromal cells. miR-29a promoted transcriptomic landscapes of redox reaction and forkhead box O (FoxO) pathways, preserving oxidation resistance protein-1 (Oxr1) and FoxO3 in old mice. In vitro, miR-29a interrupted DNA methyltransferase 3b (Dnmt3b)-mediated FoxO3 promoter methylation and senescence-associated β-galactosidase activity in aged osteoblasts. Dnmt3b inhibitor 5′-azacytosine, antioxidant N-acetylcysteine, or Oxr1 recombinant protein attenuated loss in miR-29a and FoxO3 to mitigate oxidative stress, senescence, and mineralization matrix underproduction. Taken together, miR-29a promotes Oxr1, compromising oxidative stress and FoxO3 loss to delay osteoblast aging and bone loss. This study sheds light on a new antioxidation mechanism by which miR-29a protects against osteoblast aging and highlights the remedial effects of miR-29a on osteoporosis.

scholarly journals The Protective Effect of Sika Deer Antler Protein on Gentamicin-Induced Nephrotoxicity in Vitro and in Vivo

2018 ◽  
Vol 50 (3) ◽  
pp. 841-850 ◽  
Author(s):  
Hang Sun ◽  
Huihai Yang ◽  
Haonan Ruan ◽  
Wei Li ◽  
Xinhong He ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Sika Deer ◽  
Kidney Injury ◽  
Hek293 Cells ◽  
Inflammatory Factors ◽  
Oxidative Stress Marker ◽  
Renal Protection ◽  
Deer Antler

Background/Aims: Sika deer (Cervus nippon Temminck) antler is traditional animal medicine of renal protection in East Asia. This study measured the effect of sika deer antler protein (SDAPR) on gentamicin (GM)-induced cytotoxicity in HEK293 cells, and investigated the effect of SDAPR against GM-induced nephrotoxicity in mice. Methods: HEK293 cells viability and oxidative stress were measured in HEK293 cells while flow cytometry was used for apoptosis analysis. The acute kidney injury biomarkers, kidney injury molecule-1 (KIM-1), neutrophil gelatinase-associated lipocalin (NGAL) and cystatin c (Cys-C), were repeatedly measured by ELISA assay. ICR male mice were randomly assigned six groups: Control, GM with vehicle, single SDAPR, GM with SDAPR at three concentrations 50, 100, 200 mg/kg/d, p.o., 10 d. GM was injected for 8 consecutive days (100 mg/kg/d, i.p.). Renal function, oxidative stress and levels of inflammatory factors were measured in vivo. Renal tissues were stained with H&E to observe pathological changes. Results: Pretreatment with SDAPR (0.5-4.0 mg/mL) significantly improved cell viability. Treatment with SDAPR could reduce KIM-1, NGAL and Cys-C activity. SDAPR could improve antioxidant defense and attenuated apoptosis on HEK293 cells. SDAPR also ameliorated GM-induced histopathologic changes, and decreased blood urea nitrogen (BUN) and serum creatinine (Cr). Additionally, SDAPR significantly regulated oxidative stress marker and interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) inflammatory cytokines. Conclusion: These results show that SDAPR could be an effective dietary supplement to relieve GM-induced nephrotoxicity by improved antioxidase activity, suppressed inflammation, and inhibited apoptosis in vitro and vivo.

Aged Citrus Peel (Chenpi) Prevents Acetaminophen-Induced Hepatotoxicity by Epigenetically Regulating Nrf2 Pathway

2019 ◽  
Vol 47 (08) ◽  
pp. 1833-1851
Author(s):  
Zi-Han Lin ◽  
Yen-Fan Chan ◽  
Min-Hsiung Pan ◽  
Yen-Chen Tung ◽  
Zheng-Yuan Su
Keyword(s):  
Oxidative Stress ◽  
Dna Methyltransferase ◽  
Chinese Herb ◽  
Luciferase Reporter ◽  
Luciferase Reporter Gene ◽  
Citrus Peel ◽  
Nrf2 Pathway ◽  
Cellular Defense ◽  
Excessive Consumption

Excessive consumption of analgesic drug acetaminophen (APAP) can cause severe oxidative stress-mediated liver injury. Here, we investigated the protective effect and mechanism of aged citrus peel (Chenpi, CP), a Chinese herb usually used in foods in Asia, against APAP-induced hepatotoxicity. CP water (CP-WE), ethanolic (CP-EE), and water extraction residue ethanolic (CP-WREE) extracts were prepared. We found that CP-WREE contained higher content of bioactive flavonoids, including narirutin, nobiletin, and tangeretin, and more effectively enhanced the Nrf2 pathway in ARE-luciferase reporter gene transfected human HepG2-C8 cells. In mouse AML-12 hepatocytes, CP-WREE minimized APAP-induced damage and lipid peroxidation and increased mRNA and protein expressions of Nrf2 and its downstream defense enzymes (HO-1, NQO1, and UGT1A). CP-WREE also downregulated HDACs and DNMTs, upregulated KDMs, and increased the unmethylated Nrf2 promoter level. Additionally, CP-WREE blocked in vitro DNA methyltransferase activity. Taken together, CP-WREE might attenuate oxidative stress-induced hepatotoxicity through epigenetically regulating Nrf2-mediated cellular defense system.

scholarly journals Constitutive Activation of β-Catenin in Differentiated Osteoclasts Induces Bone Loss in Mice

2018 ◽  
Vol 48 (5) ◽  
pp. 2091-2102 ◽  
Author(s):  
Xin Sui ◽  
Shijian Deng ◽  
Mengmeng Liu ◽  
Linlin Fan ◽  
Yunfei Wang ◽  
...  
Keyword(s):  
Bone Loss ◽  
Bone Mass ◽  
Bone Growth ◽  
Osteoclast Differentiation ◽  
Marker Genes ◽  
Tartrate Resistant Acid Phosphatase ◽  
Bone Homeostasis ◽  
Micro Computed Tomography ◽  
Constitutive Activation

Background/Aims: Activation of the Wnt/β-catenin signalling pathway has been widely investigated in bone biology and shown to promote bone formation. However, its specific effects on osteoclast differentiation have not been fully elucidated. Our study aimed to identify the role of β-catenin in osteoclastogenesis and bone homeostasis. Methods: In the present study, exon 3 in the β-catenin gene (Ctnnb1) allele encoding phosphorylation target serine/threonine residues was flanked by floxP sequences. We generated mice exhibiting conditional β-catenin activation (Ctsk-Cre;Ctnnb1flox(exon3)/+, designated CA-β-catenin) by crossing Ctnnb1flox(exon3)/flox(exon3) mice with osteoclast-specific Ctsk-Cre mice. Bone growth and bone mass were analysed by micro-computed tomography (micro-CT) and histomorphometry. To further examine osteoclast activity, osteoclasts were induced from bone marrow monocytes (BMMs) isolated from CA-β-catenin and Control mice in vitro. Osteoclast differentiation was detected by tartrate-resistant acid phosphatase (TRAP) staining, immunofluorescence staining and reverse transcription-quantitative PCR (RT–qPCR) analysis. Results: Growth retardation and low bone mass were observed in CA-β-catenin mice. Compared to controls, CA-β-catenin mice had significantly reduced trabecular bone numbers under growth plates as well as thinner cortical bones. Moreover, increased TRAP-positive osteoclasts were observed on the surfaces of trabecular bones and cortical bones in the CA-β-catenin mice; consistent results were observed in vitro. In the CA-β-catenin group, excessive numbers of osteoclasts were induced from BMMs, accompanied by the increased expression of osteoclast-associated marker genes. Conclusion: These results indicated that the constitutive activation of β-catenin in osteoclasts promotes osteoclast formation, resulting in bone loss.

scholarly journals NADPH Oxidase (Rboh) Activity is Up Regulated during Sweet Pepper (Capsicum annuum L.) Fruit Ripening

Antioxidants ◽  
2019 ◽  
Vol 8 (1) ◽  
pp. 9 ◽  
Author(s):  
Ángela Chu-Puga ◽  
Salvador González-Gordo ◽  
Marta Rodríguez-Ruiz ◽  
José M. Palma ◽  
Francisco J. Corpas
Keyword(s):  
Oxidative Stress ◽  
Nadph Oxidase ◽  
Capsicum Annuum ◽  
Fruit Ripening ◽  
Biochemical Characterization ◽  
Sweet Pepper ◽  
Oxidative Stress Marker ◽  
Vitro Assay ◽  
Capsicum Annuum L

In plants, NADPH oxidase (NOX) is also known as a respiratory burst oxidase homolog (Rboh). This highly important enzyme, one of the main enzymatic sources of superoxide radicals (O2•−), is involved in the metabolism of reactive oxygen and nitrogen species (ROS and RNS), which is active in the non-climacteric pepper (Capsicum annuum L.) fruit. We used sweet pepper fruits at two ripening stages (green and red) to biochemically analyze the O2•−-generating Rboh activity and the number of isozymes during this physiological process. Malondialdehyde (MDA) content, an oxidative stress marker, was also assayed as an index of lipid peroxidation. In red fruits, MDA was observed to increase 2-fold accompanied by a 5.3-fold increase in total Rboh activity. Using in-gel assays of Rboh activity, we identified a total of seven CaRboh isozymes (I–VII) which were differentially modulated during ripening. CaRboh-III and CaRboh-I were the most prominent isozymes in green and red fruits, respectively. An in vitro assay showed that CaRboh activity is inhibited in the presence of nitric oxide (NO) donors, peroxynitrite (ONOO−) and glutathione (GSH), suggesting that CaRboh can undergo S-nitrosation, Tyr-nitration, and glutathionylation, respectively. In summary, this study provides a basic biochemical characterization of CaRboh activity in pepper fruits and indicates that this O2•−-generating Rboh is involved in nitro-oxidative stress associated with sweet pepper fruit ripening.

scholarly journals Sclareol prevents ovariectomy-induced bone loss in vivo and inhibits osteoclastogenesis in vitro via suppressing NF-κB and MAPK/ERK signaling pathways

2019 ◽  
Vol 10 (10) ◽  
pp. 6556-6567 ◽  
Author(s):  
Haiming Jin ◽  
Zhenxuan Shao ◽  
Qingqing Wang ◽  
Jiansen Miao ◽  
Xueqin Bai ◽  
...  
Keyword(s):  
Bone Loss ◽  
Bone Mass ◽  
Postmenopausal Women ◽  
Postmenopausal Osteoporosis ◽  
Bone Quality ◽  
Progressive Disease ◽  
Erk Signaling ◽  
Low Bone Mass

Postmenopausal osteoporosis (PMO) is a progressive disease occurring in elderly postmenopausal women that is characterized by low bone mass and impaired bone quality.

scholarly journals The Fungal Metabolite (+)-Terrein Abrogates Ovariectomy-Induced Bone Loss and Receptor Activator of Nuclear Factor-κB Ligand–Induced Osteoclastogenesis by Suppressing Protein Kinase-C α/βII Phosphorylation

2021 ◽  
Vol 12 ◽  
Author(s):  
Kyosuke Sakaida ◽  
Kazuhiro Omori ◽  
Masaaki Nakayama ◽  
Hiroki Mandai ◽  
Saki Nakagawa ◽  
...  
Keyword(s):  
Bone Loss ◽  
Bone Mass ◽  
Bone Metabolism ◽  
Osteoclast Differentiation ◽  
Nuclear Factor Κb ◽  
Common Disease ◽  
Mouse Bone Marrow ◽  
Nuclear Factor ◽  
Receptor Activator

Osteoporosis is a common disease characterized by a systemic impairment of bone mass and microarchitecture that results in fragility fractures. Severe bone loss due to osteoporosis triggers pathological fractures and consequently decreases the daily life activity and quality of life. Therefore, prevention of osteoporosis has become an important issue to be addressed. We have reported that the fungal secondary metabolite (+)-terrein (TER), a natural compound derived from Aspergillus terreus, has shown receptor activator of nuclear factor-κB ligand (RANKL)–induced osteoclast differentiation by suppressing nuclear factor of activated T-cell 1 (NFATc1) expression, a master regulator of osteoclastogenesis. TER has been shown to possess extensive biological and pharmacological benefits; however, its effects on bone metabolism remain unclear. In this study, we investigated the effects of TER on the femoral bone metabolism using a mouse-ovariectomized osteoporosis model (OVX mice) and then on RANKL signal transduction using mouse bone marrow macrophages (mBMMs). In vivo administration of TER significantly improved bone density, bone mass, and trabecular number in OVX mice (p < 0.01). In addition, TER suppressed TRAP and cathepsin-K expression in the tissue sections of OVX mice (p < 0.01). In an in vitro study, TER suppressed RANKL-induced phosphorylation of PKCα/βII, which is involved in the expression of NFATc1 (p < 0.05). The PKC inhibitor, GF109203X, also inhibited RANKL-induced osteoclastogenesis in mBMMs as well as TER. In addition, TER suppressed the expression of osteoclastogenesis-related genes, such as Ocstamp, Dcstamp, Calcr, Atp6v0d2, Oscar, and Itgb3 (p < 0.01). These results provide promising evidence for the potential therapeutic application of TER as a novel treatment compound against osteoporosis.

scholarly journals Neural Oxidant-stress by Azadirachtin Induces Anti-oxidative Enzymes Evincing Biomarker Potential in Paddy Pest, Spathosternum prasiniferum prasiniferum (Orthoptera:Acridoidea)

2019 ◽  
pp. 1-10
Author(s):  
Balaram Manna ◽  
Smarajit Maiti ◽  
Amlan Das
Keyword(s):  
Oxidative Stress ◽  
Antioxidant Enzymes ◽  
Growth Regulation ◽  
Oxidant Stress ◽  
Oxidative Enzymes ◽  
Oxidative Stress Marker ◽  
Stress Marker ◽  
The Impact

Azadirachtin (C35H44O16/AZT) develops antifeedancy/growth-regulation/fecundity-suppression/ sterilization/oviposition/repellence and deformity in insect via biochemical/cellular changes and causes their death. Agricultural productivity/quality/eco-sustainability is concerned to this issue. ROS are cytotoxic-factors generated in invertebrates in stress-conditions. The present in-vivo/in-vitro study aimed to investigate the impact of dose dependant AZT toxicity on oxidative-stress-marker (alkaline-phosphatise/ALP; thiobarbituric-acid-reactive-substances/TBARS; non-protein-soluble-thiols/NPSH; acetyl-cholinesterase/AChE) and antioxidant-enzyme activity (superoxide-dismutase/SOD; catalase/CAT; glutathione-peroxidise/GPx; amylase) in brain/hemolymph of Spathosternum prasiniferum prasiniferum (Walker,1871) (Orthoptera:Acridoidea). Acridids are highly abundant and bio-indicator of grassland-ecosystem. During cultivation, insects are exposed (dose/time dependant) to AZT. AZT developed restlessness, jerky-movements and swarming-movements in the insects. It promoted oxidative-stress-marker in brain/hemolymphin both sexes but female had significantly stimulated antioxidant-enzymes to overcome cellular-stress. Increase of brain TBARS, antioxidant-enzymes and decrease in NPSH by AZT indicates oxidative-stress induction in this species. In several instances damage to the brain DNA was noticed. In general female insect responded more intensely with some prominent adaptive strategies.

scholarly journals Hydroxysafflor yellow A promotes osteogenesis and bone development via epigenetically regulating β-catenin and prevents ovariectomy-induced bone loss

2020 ◽  
Author(s):  
Peng Wang ◽  
Wang Min ◽  
Tingling Zhuo ◽  
Ying Li ◽  
Lin Weiping ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Bone Loss ◽  
Bone Development ◽  
Convincing Evidence ◽  
Bone Diseases ◽  
Chick Embryos ◽  
Rt Pcr ◽  
Hydroxysafflor Yellow A ◽  
Sd Rats

Abstract In clinical treatment, there is increasingly prevalent that traditional Chinese medicine treats common bone diseases including osteoporosis. Hydroxy safflor yellow A (HSYA), one of the essential compounds of Safflower, has strong effects to scavenge oxidative stress and inhibit apoptosis. It has been used as the therapy for thrombus, myocardial ischemia, and inflammation, but its effect on osteoporosis has not been explored. In this study, we found HSYA could enhance the cell viability and promote osteogenesis of hBMSC in vitro. Mechanistically, HSYA could increase the expression of β-catenin leading to its accumulation in the nucleus and activation of down-stream targets to promote osteogenesis. In addition, RNAseq and quantitative RT-PCR showed KDM7A was significantly increased by HSYA.The occupancy of H3K27me2 on β-catenin promoter was significantly decreased by HSYA, which could be reversed by silencing endogenous KDM7A. More importantly, HSYA could promote bone development in chick embryos and prevent ovariectomy(OVX)-induced bone loss in SD rats. Taken together, our study has shown convincing evidence that HSYA can promote osteogenesis and bone development via epigenetically regulating β-catenin and prevents ovariectomy-induced bone loss. HSYA might be used to treat some skeletal diseases such as osteoporosis.

scholarly journals HDAC6 inactivates Runx2 promoter to block osteogenesis of bone marrow stromal cells in age-related bone loss of mice

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Chao Ma ◽  
Juan Gao ◽  
Jun Liang ◽  
Weixiang Dai ◽  
Zhenfei Wang ◽  
...  
Keyword(s):  
Bone Loss ◽  
Bone Formation ◽  
Osteogenic Differentiation ◽  
Differentiation Potential ◽  
Runx2 Expression ◽  
Aged Mice ◽  
Age Related ◽  
Old Mice

Abstract Background Senile osteoporosis can cause bone fragility and increased risk for fractures and has been one of the most prevalent and severe diseases affecting the elderly population worldwidely. The underlying mechanisms are currently intensive areas of investigation. In age-related bone loss, decreased bone formation overweighs increased bone resorption. The molecular mechanisms underlying defective bone formation in age-related bone loss are not completely understood. In particular, the specific role of histone acetylation in age-related bone loss has not been examined thoroughly. Methods We employed 6- and 18-month-old mice to investigate the mechanisms of defective bone formation in age-related bone loss. Bone marrow stromal cells (BMSCs) were induced to undergo in vitro osteogenic differentiation. Chromatin immunoprecipitation (ChIP) was used to investigate the binding of histone deacetylases (HDACs) on Runx2 promoter in BMSCs. Luciferase reporter and transient transfection assay were employed to study Runx2 gene expression modulation by HDAC and androgen receptor (AR). siRNA and HDAC6 inhibitor, Tubastatin A, were used to inhibit HDAC6 in vitro. And systemic administration of Tubastatin A was used to block HDAC6 in vivo. Results Age-related trabecular bone loss was observed in 18-month-old mice compared with 6-month-old mice. In vitro osteogenic differentiation potential of BMSCs from 18-month-old mice was weaker than 6-month-old mice, in which there was Runx2 expression inactivation in BMSCs of 18-month-old mice compared with 6-month-old mice, which was attributable to HDAC6-mediated histone hypoacetylation in Runx2 promoter. There was competitive binding of HDAC6 and AR on Runx2 promoter to modulate Runx2 expression in BMSCs. More importantly, through siRNA- or specific inhibitor-mediated HDAC6 inhibition, we could activate Runx2 expression, rescue in vitro osteogenesis potential of BMSCs, and alleviate in vivo age-related bone loss of mice. Conclusion HDAC6 accumulation and histone hypoacetylation on Runx2 promoter contributed to the attenuation of in vitro osteogenic differentiation potential of BMSCs from aged mice. Through HDAC6 inhibition, we could activate Runx2 expression and osteogenic differentiation potential of BMSCs from aged mice and alleviate the age-related bone loss of aged mice. Our study will benefit not only for understanding the age-related bone loss, but also for finding new therapies to treat senile osteoporosis.

103 RAMAN MICROSPECTROSCOPY AS A TOOL TO DETECT MOLECULAR MODIFICATIONS INDUCED BY AGING-RELATED OXIDATIVE STRESS IN MOUSE OOCYTES

2013 ◽  
Vol 25 (1) ◽  
pp. 199
Author(s):  
O. Murrone ◽  
M. Piccinini ◽  
C. Tatone ◽  
G. Di Emidio ◽  
S. Ledda ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Principal Component Analysis ◽  
Raman Spectroscopy ◽  
Principal Component ◽  
Component Analysis ◽  
Oocyte Quality ◽  
Markers Of Oxidative Stress ◽  
Group A ◽  
Old Mice

The conditions of oxidative stress that can be generated during physiological events, such as post-ovulatory aging and reproductive aging, as well as by the PMA procedures, can seriously degrade the oocyte developmental competence. The ability to identify predictive markers of oxidative stress using noninvasive techniques may provide a useful diagnostic tool for the assessment of oocyte quality. The aim of the present work is to evaluate the potential of Raman spectroscopy (RMN) as a tool to detect molecular modifications induced by aging-related oxidative stress in mouse oocytes. The research was carried out using CD-1 mice; at the age of 4 to 8 weeks (young mice) and 48 to52 weeks (old mice), females were superovulated and oocytes at metaphase II stage were recovered from oviducts. The MII oocytes from young animals were divided into 3 experimental groups: (A) young oocytes, processed immediately after collection; (B) in vitro aged oocytes, cultured in vitro for 10 h before processing; (C) oxidative-stressed oocytes, exposed to 10 mM hydrogen peroxide for 2 min before processing (oocytes with a fully oxidized status). Oocytes from reproductively old mice were referred to as old oocytes (D). After fixation in 3.7% paraformaldehyde, oocytes (n = 10 for each group) were immersed in a 50-µL drop of PBS on quartz windows and analyzed using a Bruker Senterra confocal Raman microscope. Measurements were performed by recording 3 line scans across the oocyte with 5-µm step size, totalling 32 point spectra for each oocyte. The spectra were statistically analyzed using principal component analysis. Principal component analysis showed a clear discrimination between the spectra of young oocytes (A), in vitro aged oocytes (B), oxidative-stressed oocytes (C), and old oocytes (D). Compared with the control group (A), B, C, and D groups revealed significant differences in the bands attributable to lipid components; specifically, a reduction in the intensity of the peaks at 1653 and 1602 cm–1 (stretching of the C = C bond) and of the peaks at 1485, 1462, 1437, 1396 cm–1 (CH3-CH2 vibration) was recorded. With regard to the protein component, spectra of B, C, and D groups showed modifications in the intensities of peaks 1297 and 850 cm–1, which refer respectively to amide III and to CNC symmetric stretching compared with group A. Principal component analysis also revealed an overlap between the spectra of in vitro aged oocytes, old oocytes, and oxidative-stressed oocytes, suggesting that the molecular damage caused by ageing has similar characteristics to chemically induced oxidative damage. In conclusion, the results of our study show that Raman spectroscopy is a valuable tool for the identification of molecular biochemical markers of oxidative stress. This technique could represent a highly informative method of investigation to evaluate the oocyte quality in response to various stress conditions (in vitro maturation, aging, cryopreservation, and so on) that may negatively affect its potential development.

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