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Blueberry Diets during Early Development Only Is Sufficient to Prevent Senescence of Osteoblasts and Bone Loss in Adulthood

ABSTRACT: Appropriate nutrition during early development is essential for optimal bone mass accretion; however, linkage between early nutrition, childhood bone mass and prevention of bone loss later in life has not been extensively studied. In this report, we have demonstrated several fundamental issues in the field. 1) A significant prevention of ovariectomy (OVX) -induced bone loss from adult rats can occur with only 14 days consumption of a blueberry-containing diet immediately prior to puberty. 2) The molecular mechanisms underlying these effects involve increased myosin production and preserved a shuttle for transcription factors such as Runx2 from cytoplasm to nucleolus which stimulates osteoblast differentiation and reduces mesenchymal stromal cell senescence. 3) The effects of blueberry diet on preserving fidelity of osteoblast differentiation also overcome reduced osteoblast differentiation and activity due to OVX-induced degradation of collagen matrix.

ORGANISM(S): Rattus norvegicus

PROVIDER: GSE30081 | GEO | 2012/07/01

SECONDARY ACCESSION(S): PRJNA144067

REPOSITORIES: GEO

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Blueberry Diets during Early Development Only Is Sufficient to Prevent Senescence of Osteoblasts and Bone Loss in Adulthood

Project description:Appropriate nutrition during early development is essential for optimal bone mass accretion; however, linkage between early nutrition, childhood bone mass and prevention of bone loss later in life has not been extensively studied. In this report, we have demonstrated several fundamental issues in the field. 1) A significant prevention of ovariectomy (OVX) -induced bone loss from adult rats can occur with only 14 days consumption of a blueberry-containing diet immediately prior to puberty. 2) The molecular mechanisms underlying these effects involve increased myosin production and preserved a shuttle for transcription factors such as Runx2 from cytoplasm to nucleolus which stimulates osteoblast differentiation and reduces mesenchymal stromal cell senescence. 3) The effects of blueberry diet on preserving fidelity of osteoblast differentiation also overcome reduced osteoblast differentiation and activity due to OVX-induced degradation of collagen matrix. Bone quality was compared among casein control diet sham operated, casein diet ovariectomized, long term BB diet ovariectomized, and short term BB diet ovariectomized female rats

2012-06-30 | E-GEOD-30081 | biostudies-arrayexpress

High Fat Diet (HFD)-Induced Obesity Augments the Deleterious Effects of Estrogen Deficiency on Bone: Evidence from ovariectomized Mice.

Project description:There is an increasing clinical evidence that obesity exerts deleterious effects on the skeleton. While obesity coexists with estrogen deficiency in postmenopausal women, their combined effects on the skeleton are poorly studied. Thus, we investigated the impact of high-fat diet (HFD) on bone and metabolism of ovariectomized (OVX) female mice (C57BL/6J). OVX or sham operated mice were fed either HFD (60%fat) or normal diet (ND) (10%fat) for 12 weeks. HFD-OVX group exhibited pronounced increase in body weight (~86% in HFD and ~122% in HFD-OVX, p<0.0005) and impaired glucose tolerance. Bone microCT-scanning revealed a pronounced decrease in trabecular bone volume/total volume (BV/TV) in HFD-OVX (15.6±0.48% in HFD and 37.5±0.235% in HFD-OVX, p<0.005) and expansion of bone marrow adipose tissue (BMAT) (+60.7±9.9% in HFD vs +79.5±5.86% in HFD-OVX, p<0.005). Mechanistically, HFD-OVX treatment led to upregulation of genes markers of senescence, bone resorption, adipogenesis and inflammation and downregulation of gene markers of bone formation and bone development. Similarly, HFD- OVX treatment resulted in significant changes in bone tissue levels of Purine/Pyrimidine and Glutamate metabolisms, known to play a regulatory role in bone metabolism. Obesity and estrogen deficiency exert combined deleterious effects on bone resulting in accelerated cellular senescence, expansion of BMAT and impaired bone formation leading to decreased bone mass. Our results suggest that obesity may increase bone fragility in post-menopausal women.

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Inhibiting glutaminase exerts opposite effects on ovariectomy-induced and age-related reductions in murine bone mass

Project description:Recent studies have provided links between glutamine metabolism and bone remodeling, but little is known about its role in primary osteoporosis progression. We aimed to determine the effects of inhibiting glutaminase (GLS) on two types of primary osteoporosis and elucidate the related metabolism. To address this issue, age-related and ovariectomy (OVX)-induced bone loss mouse models were used to study the in vivo effects of CB-839, a potent and selective GLS inhibitor, on bone mass and bone turnover. We also studied the metabolic profile changes related with aging and GLS inhibition in primary bone marrow stromal cells (BMSC) and that related with OVX and GLS inhibition in primary bone marrow-derived monocytes (BMM). Besides, we studied the possible metabolic processes mediating GLS blockade effects during aging-impaired osteogenic differentiation and RANKL-induced osteoclast differentiation respectively via in vitro rescue experiments. We found that inhibiting GLS via CB-839 prevented OVX-induced bone loss while aggravated age-related bone loss. Further investigations showed that effects of CB-839 treatment on bone mass were associated with alterations of bone turnover. Moreover, CB-839 treatment altered metabolic profile in different orientations between BMSC of aged mice and BMM of ovariectomized mice. In addition, rescue experiments revealed that different metabolic processes mediated glutaminase blockade effects between aging-impaired osteogenic differentiation and RANKL-induced osteoclast differentiation. Taken together, our data demonstrated the different outcomes caused by CB-839 treatment between two types of osteoporosis in mice, which were tightly connected to the suppressive effects on both aging-impaired osteoblastogenesis and OVX-enhanced osteoclastogenesis mediated by different metabolic processes downstream of glutaminolysis.

2024-06-17 | MTBLS9415 | MetaboLights

DLK1 Is a Novel Regulator of Bone Mass That Mediates Estrogen-Deficiency Induced Bone Loss in Mice

Project description:DLK1/FA-1 (delta-like 1/fetal antigen-1) is a transmembrane protein belonging to Notch/Delta family that acts as a membrane-associated or a soluble protein to regulate regeneration of a number of adult tissues. Here, we examined the role of DLK1/FA-1 in bone biology using osteoblast-specific-Dlk1 over-expressing mice (Col1-Dlk1). Col1-Dlk1 mice displayed growth retardation and significantly reduced total body weight and bone mineral density (BMD). Î¼CT-scanning revealed a reduced trabecular and cortical bone volume fraction. Tissue-level histomorphometric analysis demonstrated decreased bone formation rate and enhanced bone resorption in Col1-Dlk1 as compared to WT. At a cellular level, DLK1 markedly reduced the total number of bone marrow (BM)-derived CFU-F, as well as their osteogenic capacity. In a number of in vitro culture systems, DLK1 stimulated osteoclastogenesis indirectly through osteoblast-dependent increased production of pro-inflammatory bone resorbing cytokines (e.g, Il7, Tnfa and Ccl3). We found that ovariectomy (ovx)-induced bone loss was associated with increased production of DLK1 in bone marrow by activated T-cells. However, Dlk1-/- mice were protected from ovx-induced bone loss. Thus, we identified DLK1 as a novel regulator of bone mass that function to inhibit bone formation and to stimulate bone resorption. Increasing DLK1 production by T-cells under estrogen deficiency suggests its possible use as a therapeutic target for preventing postmenopausal bone loss. Calvarial osteoblasts were grown from neonatal mice overexpressing Dlk1 and their non-transgenic littermate controls. Three separate cultures from each of the two genotypes were combined and analysed by Affymetrix microarray MOE430 2.0.

2010-10-15 | E-GEOD-22113 | biostudies-arrayexpress

Identification of conserved and novel microRNAs in blueberry

Project description:In the present study, we employed the high-throughput sequencing technology to profile miRNAs in blueberry fruits. A total of 9,992,446 small RNA tags with sizes ranged from 18 to 30 nt were obtained, indicating that blueberry fruits have a large and diverse small RNA population. Bioinformatic analysis has identified 412 conserved miRNAs, which belong to 20 families, and 57 predicted novel miRNAs likely unique to blueberries. Among them, expression profiles of 5 conserved miRNAs were validated by stem loop qRT-PCR. Furthermore, the potential target genes of the abundant conserved and novel miRNAs were predicted and subjected for Gene Ontology (GO) annotation. Enrichment analysis of the GO-represented biological processes and molecular functions revealed that these target genes were involved in a wide range of metabolic and developmental processes. This study is the first report on genome-wide miRNA profile analysis in blueberry and it provides a useful resource for further elucidation of the functional roles of miRNAs during fruit development and ripening.

2017-06-29 | GSE94411 | GEO

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