scholarly journals Transcriptome analysis of osteoblasts in an ovariectomized mouse model in response to physical exercise

2018 ◽  
Vol 7 (11) ◽  
pp. 601-608 ◽  
Author(s):  
W-B. Hsu ◽  
W-H. Hsu ◽  
J-S. Hung ◽  
W-J. Shen ◽  
R. W-W. Hsu
Keyword(s):  
Physical Exercise ◽  
Mouse Model ◽  
Transcriptome Analysis ◽  
Mineral Density ◽  
Gene Expressions ◽  
Vitro Assay ◽  
Ovariectomized Mouse ◽  
Ovariectomized Mice ◽  
Positive Effect

ObjectivesOsteoporosis is a metabolic disease resulting in progressive loss of bone mass as measured by bone mineral density (BMD). Physical exercise has a positive effect on increasing or maintaining BMD in postmenopausal women. The contribution of exercise to the regulation of osteogenesis in osteoblasts remains unclear. We therefore investigated the effect of exercise on osteoblasts in ovariectomized mice.MethodsWe compared the activity of differentially expressed genes of osteoblasts in ovariectomized mice that undertook exercise (OVX+T) with those that did not (OVX), using microarray and bioinformatics.ResultsMany inflammatory pathways were significantly downregulated in the osteoblasts after exercise. Meanwhile, IBSP and SLc13A5 gene expressions were upregulated in the OVX+T group. Furthermore, in in vitro assay, IBSP and SLc13A5 mRNAs were also upregulated during the osteogenic differentiation of MC3T3-E1 and 7F2 cells.ConclusionThese findings suggest that exercise may not only reduce the inflammatory environment in ovariectomized mice, indirectly suppressing the overactivated osteoclasts, but may also directly activate osteogenesis-related genes in osteoblasts. Exercise may thus prevent the bone loss caused by oestrogen deficiency through mediating the imbalance between the bone resorptive activity of osteoclasts and the bone formation activity of osteoblasts. Cite this article: W-B. Hsu, W-H. Hsu, J-S. Hung, W-J. Shen, R. W-W. Hsu. Transcriptome analysis of osteoblasts in an ovariectomized mouse model in response to physical exercise. Bone Joint Res 2018;7:601–608. DOI: 10.1302/2046-3758.711.BJR-2018-0075.R2.

scholarly journals Anti-Osteoporotic Activity of Pueraria lobata Fermented with Lactobacillus paracasei JS1 by Regulation of Osteoblast Differentiation and Protection against Bone Loss in Ovariectomized Mice

Fermentation ◽  
2021 ◽  
Vol 7 (3) ◽  
pp. 186
Author(s):  
Seon Yu Kim ◽  
Hee-Ju Lee ◽  
Taehyun Kim ◽  
Yeong-Geun Lee ◽  
Jeong Eun Kwon ◽  
...  
Keyword(s):  
Bone Loss ◽  
Bone Mineral ◽  
Lactobacillus Paracasei ◽  
Calcium Deposition ◽  
Pueraria Lobata ◽  
Mineral Density ◽  
Vitro Assay ◽  
Ovariectomized Mice ◽  
Mg63 Cells

Osteoporosis is the most common bone disease associated with low bone mineral density. It is the process of bone loss and is most commonly caused by decreased estrogen production in women, particularly after menopause. Pueraria lobata, which contains various metabolites, especially isoflavone, is widely known as regulator for bone mineral contents. In this study, the effects of the P. lobata extract (PE) with or without fermentation with Lactobacillus paracasei JS1 (FPE) on osteoporosis were investigated in vitro and in vivo. The effects of PE and FPE on human osteoblastic MG63 cells, RAW 264.7 cells, and ovariectomized (OVX)-induced model mice were analyzed at various ratios. We found that FPE increased calcium deposition and inhibited bone resorption by in vitro assay. Furthermore, treatment with PE and FPE has significantly restored destroyed trabecular bone in the OVX-induced bone loss mouse model. Overall, FPE demonstrated bioactivity to prevent bone loss by decreasing bone turnover.

scholarly journals IMPORTÂNCIA DA PREPARAÇÃO FÍSICA PARA O PACIENTE COM DOENÇA DE PARKINSON

2019 ◽  
pp. 29-43
Keyword(s):  
Quality Of Life ◽  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Physical Exercise ◽  
Muscular Strength ◽  
Review Of Literature ◽  
The Subject ◽  
Positive Effect

TEIXEIRA, M.E. e PEREIRA, J.L. Importância da preparação física para o paciente com doença de Parkinson. Revista Científica JOPEF, Vol.28, n.1, pp.29-43, 2019. Parkinson's disease (PD) is a chronic progressive neurodegenerative disease described by the first in 1897 as "tremor paralysis." Its symptoms are variable, the most characteristic being tremor of the hands and loss of balance and muscular strength. It usually affects men over the age of 60, but there are forms that can occur in younger individuals. The progression of symptoms causes the quality of life of the patient to deteriorate significantly, leading to the inability to perform daily activities. In addition to pharmacological treatment, physical exercise has been indicated as a way to attenuate and slow the progression of symptoms. The objective of this work is to carry out an integrative review of literature on the subject, in which articles published over the last 10 years have been analyzed, thus seeking to update the theme. In general, it was possible to perceive a positive effect of the practice of specific physical exercise programs in patients with PD, with improvement of the quality of life. In vitro studies also demonstrated the protective effect of physical exercise on the onset of the disease. Keywords: Parkinson's disease; Physical exercise; Neuroprotection; Quality of life.

scholarly journals Gut microbiota impacts bone via B.vulgatus-valeric acid-related pathways

2020 ◽  
Author(s):  
Xu Lin ◽  
Hong-Mei Xiao ◽  
Hui-Min Liu ◽  
Wan-Qiang Lv ◽  
Jonathan Greenbaum ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Valeric Acid ◽  
Individual Species ◽  
Osteoporosis Prevention ◽  
Mineral Density ◽  
Ovariectomized Mice ◽  
Chinese Cohort ◽  
Underlying Mechanisms ◽  
The Individual

AbstractAlthough gut microbiota influences osteoporosis risk, the individual species involved, and underlying mechanisms, are unknown. We performed integrative analyses in a Chinese cohort with metagenomics/targeted metabolomics/whole-genome sequencing. Bacteroides vulgatus was found negatively associated with bone mineral density (BMD), this association was validated in US Caucasians. Serum valeric acid was positively associated with BMD, and B.vulgatus causally downregulated it. Ovariectomized mice fed B.vulgatus had decreased bone formation and increased bone resorption, lower BMD and poorer bone micro-structure. Valeric acid suppressed NF-κB p65 protein production (pro-inflammatory), and enhanced IL-10 mRNA expression (anti-inflammatory), leading to suppressed maturation of osteoclast-like cells, and enhanced maturation of osteoblasts in vitro. B.vulgatus and valeric acid represent promising targets for osteoporosis prevention/treatment.

Identification and Functional Characterization of Metabolites for Bone Mass in Peri-/Post-menopausal Chinese Women

2021 ◽  
Author(s):  
Rui Gong ◽  
Hong-Mei Xiao ◽  
Yin-Hua Zhang ◽  
Qi Zhao ◽  
Kuan-Jui Su ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Bone Loss ◽  
Osteoclast Differentiation ◽  
Dodecanoic Acid ◽  
Mineral Density ◽  
Ovariectomized Mice ◽  
Post Menopausal ◽  
Functional Mechanisms

Abstract Context Although metabolic profiles appear to play an important role in menopausal bone loss, the functional mechanisms by which metabolites influence bone mineral density (BMD) during menopause are largely unknown. Objective We aimed to systematically identify metabolites associated with BMD variation and their potential functional mechanisms in peri-/post-menopausal women. Design and Methods We performed serum metabolomic profiling and whole-genome sequencing for 517 perimenopausal (16%) and early postmenopausal (84%) women aged 41 to 64 years in this cross-sectional study. Partial least squares (PLS) regression and general linear regression analysis were applied to identify BMD-associated metabolites, and weighted gene co-expression network analysis was performed to construct co-functional metabolite modules. Furthermore, we performed Mendelian randomization analysis to identify causal relationships between BMD-associated metabolites and BMD variation. Finally, we explored the effects of a novel prominent BMD-associated metabolite on bone metabolism through both in vivo/in vitro experiments. Results Twenty metabolites and a co-functional metabolite module (consisting of fatty acids) were significantly associated with BMD variation. We found dodecanoic acid (DA), within the identified module, causally decreased total hip BMD. Subsequently, the in vivo experiments might support that dietary supplementation with DA could promote bone loss, as well as increase the osteoblast and osteoclast numbers in normal/ovariectomized mice. DA treatment differentially promoted osteoblast and osteoclast differentiation, especially for osteoclast differentiation at higher concentrations in vitro (e.g.,10, 100μM). Conclusions This study sheds light on metabolomic profiles associated with postmenopausal osteoporosis risk, highlighting the potential importance of fatty acids, as exemplified by DA, in regulating BMD.

GH002: A Novel and Potent Agents for Elevating HDL-Cholesterol

2011 ◽  
Vol 340 ◽  
pp. 337-343
Author(s):  
Guo Lei
Keyword(s):  
Hepg2 Cells ◽  
Density Lipoprotein ◽  
Hdl Cholesterol ◽  
Control Group ◽  
Vitro Assay ◽  
Cholesterol Levels ◽  
Promoter Effects ◽  
Positive Effect

The aim of this study was to evaluate whether the positive effect of GH002 on high-density lipoprotein (HDL) cholesterol in vitro and in vivo. In vitro assay, effects of GH002 on apolipoprotein (apo) A-I was studied using stable-transfected HepG2 cells with recombinant vector including apoA-I promoter; Effects of GH002 on apoA-I, apoA-II and apoC-III production were determined using HepG2 cells. In vivo assay, Effects of GH002 on lipid profile were investigated in hyperlipidemic rats. The results showed that GH002 can effectively activate apoA-I promoter, enhance apoA-I and apoA-II secretion in vitro, whereas reduce apoC-III production significantly. Furthermore, after in vivo study that the hyperlipidemic rats were treated with GH002, HDL-cholesterol levels were increased significantly (P<0.01) at 2 weeks (100 mg/kg, 28.8%) and 3 weeks (30mg/kg, 19.8% and 100mg/kg, 36.4%, respectively) compared with control group. Triglyceride levels were reduced significantly at 2 and 3 weeks (19.5%, P<0.05 and 28.1%, P<0.01 respectively). Total cholesterol levels also were reduced at 3 weeks (19.1%, P<0.05) after 100mg/kg GH002 administration, but GH002 didn’t increase the ratio of liver/body weight compared with the control group at the end of the experiments. It is therefore reasonable to assume that GH002 is an effectively HDL-cholesterol enhancer by regulating apoA-I gene expression, consequently enhancing apoA-I, apoA-II secretion and reducing apoC-III production.

scholarly journals Anti-Osteoporotic Effects of Kukoamine B in Osteoblast and Osteoclast Cells and Ovariectomized Mice

2017 ◽  
Author(s):  
Eunkuk Park ◽  
Jeonghyun Kim ◽  
Mun-Chang Kim ◽  
Subin Yeo ◽  
Jieun Kim ◽  
...  
Keyword(s):  
Osteoblast Differentiation ◽  
Osteoclast Differentiation ◽  
Osteoblastic Differentiation ◽  
Nodule Formation ◽  
Mouse Bone Marrow ◽  
Mineral Density ◽  
Bone Mineral Density Loss ◽  
Ovariectomized Mice

Osteoporosis is an abnormal bone remodeling condition characterized by decreased bone density, which leads to high risks of broken bones. Previous studies have demonstrated that Lycii Radicis Cortex (LRC) extract inhibits bone loss in ovariectomized (OVX) mice by enhancing the osteoblast differentiation. A bioactive compound, Kukoamine B (KB), was identified from a fractionation of LRC extract as a candidate component responsible for an anti-osteoporotic effect. This study investigated the anti-osteoporotic effects of KB using in vitro and in vivo osteoporosis models. KB treatment significantly increased the osteoblastic differentiation and mineralized nodule formation of osteoblastic MC3T3-E1 cells, while it significantly decreased the osteoclast differentiation of primary-cultured monocytes derived from mouse bone marrow. The effects of KB on osteoblastic and osteoclastic differentiations under more physiological conditions were also examined. In the co-culture of MC3T3-E1 cells and monocytes, KB promoted osteoblast differentiation but did not affect osteoclast differentiation. For the in vivo experiments, KB significantly inhibited OVX-induced bone mineral density loss and restored the impaired bone structural properties in osteoporosis model mice. These results suggest that KB may be a potential therapeutic candidate for the treatment of osteoporosis.

scholarly journals Circaea Mollis Siebold & Zucc. Prevents Bone Loss in a Mouse Postmenopausal Osteoporosis Model by Promoting of Osteoblast Differentiation (P06-130-19)

2019 ◽  
Vol 3 (Supplement_1) ◽  
Author(s):  
Gyhye Yoo ◽  
Ji-Hye Park ◽  
Yang-Ju Son ◽  
Chang Ho Lee ◽  
Chu Won Nho
Keyword(s):  
Breast Cancer ◽  
Side Effects ◽  
Bone Loss ◽  
Postmenopausal Osteoporosis ◽  
Osteoclast Differentiation ◽  
Mineral Density ◽  
Promising Alternative ◽  
Ovariectomized Mice

Abstract Objectives Postmenopausal osteoporosis, a condition of low bone density consequent to decreased estrogen levels after menopause in women, is generally treated with hormone replacement therapy. However, long-term hormone use may cause critical side effects including breast cancer. Alternatively, phytoestrogens, which have similar structures to steroid hormones, are reported to cure postmenopausal symptoms with fewer side effects. Here, we investigated the effects of EtOH extract of Circaea mollis Siebold & Zucc. (EECM), a traditional herbal medicine in Asia that exhibits anti-arthritic activities, on postmenopausal osteoporosis. Methods In vitro model: MCF7 breast cancer cells and MC3T3-E1 pre-osteoblast cells were utilized to estimate estrogenic and osteogenic activity. Osteoblastic markers were measured by western blot and real-time PCR. In vivo model: Female mature C57BL/6 mice were ovariectomized and oral administrated with 10 mg/kg and 40 mg/kg of EECM respectively. Results EECM increased alkaline phosphatase activity and osteoblastic markers including osteoprotegerin at day 6 during mouse preosteoblast differentiation. EECM inhibited osteoclast differentiation and bone resorption in an osteoblast-osteoclast primary co-culture system via osteoprotegerin-mediated RANK/RANKL signaling. In ovariectomized mice, EECM prevented bone mineral density decrease and recovered osteoblastic molecules. Conclusions EECM enhanced the differentiation of osteoblasts via osteogenic markers and modulated RANK/RANKL signaling via an elevation of OPG from osteoblasts in vitro and in vivo. Therefore, EECM may be effective in preventing bone loss and offers a promising alternative for the nutritional management of postmenopausal osteoporosis. Funding Sources This work was supported by the Center Project for the Korea-Mongolia Science and Technology Cooperation (2U06170). Supporting Tables, Images and/or Graphs

scholarly journals Kindlin-2 regulates skeletal homeostasis by modulating PTH1R in mice

2020 ◽  
Vol 5 (1) ◽  
Author(s):  
Xuekun Fu ◽  
Bo Zhou ◽  
Qinnan Yan ◽  
Chu Tao ◽  
Lei Qin ◽  
...  
Keyword(s):  
Bone Mass ◽  
Volume Fraction ◽  
Bone Marrow Cells ◽  
Bone Matrix ◽  
Osteoblastic Cells ◽  
Mineral Density ◽  
Bone Volume Fraction ◽  
Ovariectomized Mice

AbstractIn vertebrates, the type 1 parathyroid hormone receptor (PTH1R) is a critical regulator of skeletal development and homeostasis; however, how it is modulated is incompletely understood. Here we report that deleting Kindlin-2 in osteoblastic cells using the mouse 10-kb Dmp1-Cre largely neutralizes the intermittent PTH-stimulated increasing of bone volume fraction and bone mineral density by impairing both osteoblast and osteoclast formation in murine adult bone. Single-cell profiling reveals that Kindlin-2 loss increases the proportion of osteoblasts, but not mesenchymal stem cells, chondrocytes and fibroblasts, in non-hematopoietic bone marrow cells, with concomitant depletion of osteoblasts on the bone surfaces, especially those stimulated by PTH. Furthermore, haploinsufficiency of Kindlin-2 and Pth1r genes, but not that of either gene, in mice significantly decreases basal and, to a larger extent, PTH-stimulated bone mass, supporting the notion that both factors function in the same genetic pathway. Mechanistically, Kindlin-2 interacts with the C-terminal cytoplasmic domain of PTH1R via aa 474–475 and Gsα. Kindlin-2 loss suppresses PTH induction of cAMP production and CREB phosphorylation in cultured osteoblasts and in bone. Interestingly, PTH promotes Kindlin-2 expression in vitro and in vivo, thus creating a positive feedback regulatory loop. Finally, estrogen deficiency induced by ovariectomy drastically decreases expression of Kindlin-2 protein in osteocytes embedded in the bone matrix and Kindlin-2 loss essentially abolishes the PTH anabolic activity in bone in ovariectomized mice. Thus, we demonstrate that Kindlin-2 functions as an intrinsic component of the PTH1R signaling pathway in osteoblastic cells to regulate bone mass accrual and homeostasis.

scholarly journals Efficacy of GC-376 against SARS-CoV-2 virus infection in the K18 hACE2 transgenic mouse model

2021 ◽  
Author(s):  
C. Joaquín Cáceres ◽  
Stivalis Cardenas-Garcia ◽  
Silvia Carnaccini ◽  
Brittany Seibert ◽  
Daniela S. Rajao ◽  
...  
Keyword(s):  
Mouse Model ◽  
Clinical Symptoms ◽  
Viral Loads ◽  
Antiviral Therapies ◽  
Virus Dose ◽  
Further Development ◽  
The Brain ◽  
Positive Effect

ABSTRACTThe COVID-19 pandemic caused by the Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) is the defining global health emergency of this century. GC-376 is a Mpro inhibitor with antiviral activity against SARS-CoV-2 in vitro. Using the K18-hACE2 mouse model, the in vivo antiviral efficacy of GC-376 against SARS-CoV-2 was evaluated. GC-376 treatment was not toxic in K18-hACE2 mice and produced milder tissue lesions, reduced viral loads, fewer presence of viral antigen, and reduced inflammation in comparison to vehicle-treated controls, most notably in the brain in mice challenged with a low virus dose. Although GC-376 was not sufficient to improve neither clinical symptoms nor survival, it did show a positive effect against SARS-CoV-2 in vivo. This study supports the notion that the K18-hACE2 mouse model is suitable to study antiviral therapies against SARS-CoV-2, and GC-376 represents a promising lead candidate for further development to treat SARS-CoV-2 infection.

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