scholarly journals 25-hydroxycholecalciferol reverses heat induced alterations in bone quality in finisher broilers associated with effects on intestinal integrity and inflammation

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Huaiyong Zhang ◽  
Maryam Majdeddin ◽  
Djoere Gaublomme ◽  
Bernard Taminiau ◽  
Matthieu Boone ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Bone Mass ◽  
Inflammatory Cytokines ◽  
Marker Genes ◽  
Specific Marker ◽  
Type I ◽  
Bacterial Phyla ◽  
Intestinal Integrity ◽  
Bone Formation Markers ◽  
25 Hydroxycholecalciferol

Abstract Background Alterations in ambient temperature have been associated with multiple detrimental effects on broilers such as intestinal barrier disruption and dysbiosis resulting in systemic inflammation. Inflammation and 25-hydroxycholecalciferol (25-OH-D3) have shown to play a negative and positive role, respectively, in the regulation of bone mass. Hence the potential of 25-OH-D3 in alleviating heat induced bone alterations and its mechanisms was studied. Results Heat stress (HS) directly induced a decrease in tibia material properties and bone mass, as demonstrated by lower mineral content, and HS caused a notable increase in intestinal permeability. Treatment with dietary 25-OH-D3 reversed the HS-induced bone loss and barrier leak. Broilers suffering from HS exhibited dysbiosis and increased expression of inflammatory cytokines in the ileum and bone marrow, as well as increased osteoclast number and activity. The changes were prevented by dietary 25-OH-D3 administration. Specifically, dietary 25-OH-D3 addition decreased abundance of B- and T-cells in blood, and the expression of inflammatory cytokines, especially TNF-α, in both the ileum and bone marrow, but did not alter the diversity and population or composition of major bacterial phyla. With regard to bone remodeling, dietary 25-OH-D3 supplementation was linked to a decrease in serum C-terminal cross-linked telopeptide of type I collagen reflecting bone resorption and a concomitant decrement in osteoclast-specific marker genes expression (e.g. cathepsin K), whereas it did not apparently change serum bone formation markers during HS. Conclusions These data underscore the damage of HS to intestinal integrity and bone health, as well as that dietary 25-OH-D3 supplementation was identified as a potential therapy for preventing these adverse effects.

scholarly journals Bone Formation Markers in Adults with Mild Osteogenesis Imperfecta

2007 ◽  
Vol 53 (6) ◽  
pp. 1109-1114 ◽  
Author(s):  
Tim Cundy ◽  
Anne Horne ◽  
Mark Bolland ◽  
Greg Gamble ◽  
James Davidson
Keyword(s):  
Alkaline Phosphatase ◽  
Bone Formation ◽  
Bone Mass ◽  
Osteogenesis Imperfecta ◽  
Plasma Concentrations ◽  
Bone Alkaline Phosphatase ◽  
Type I ◽  
Low Bone Mass ◽  
Bone Formation Markers ◽  
Discriminant Ability

Abstract Background: Plasma concentrations of procollagen peptides are decreased in osteogenesis imperfecta (OI), whereas other bone formation markers may be increased. We examined the utility of combining these markers in the diagnosis of OI in adults. Methods: We measured plasma concentrations of procollagen-1 N-peptide (P1NP), osteocalcin, and bone alkaline phosphatase in 24 patients with nondeforming OI, 25 patients with low bone mass due to other causes, and 38 age- and sex-matched controls. The discriminant ability of various test combinations was assessed by the construction of ROC curves. Results: The median (range) ratio of osteocalcin to P1NP was significantly greater in patients with type I OI [1.75 (0.80–3.86)] than in controls [0.59 (0.34–0.90)] and patients with other causes of low bone mass [0.48 (0.05–1.38); P <0.0001]. This ratio allowed nearly complete differentiation between healthy controls and patients with type I OI, but not patients with type IV OI. With a cutoff of 0.97 for osteocalcin:P1NP, the sensitivity and specificity were maximized at 95% (95% CI 76%–100%) and 88% (69%–97%), respectively, for patients with other causes of low bone mass vs those with type I OI only. For patients with other causes of low bone mass vs all OI patients, sensitivity and specificity were 83% (63%–95%) and 88% (69%–97%), respectively. The addition of bone alkaline phosphatase data did not improve the discriminant ability of the osteocalcin:P1NP ratio. Conclusions: The osteocalcin:P1NP ratio is a sensitive and specific test for type I OI in adults, but it has less utility in the diagnosis of other types of nondeforming OI.

scholarly journals Effects of Oral Anticoagulant Therapy on Gene Expression in Crosstalk between Osteogenic Progenitor Cells and Endothelial Cells

2019 ◽  
Vol 8 (3) ◽  
pp. 329 ◽  
Author(s):  
Luca Dalle Carbonare ◽  
Monica Mottes ◽  
Anna Brunelli ◽  
Michela Deiana ◽  
Samuele Cheri ◽  
...  
Keyword(s):  
Gene Expression ◽  
Bone Marrow ◽  
Endothelial Cells ◽  
Anticoagulant Therapy ◽  
Type I Collagen ◽  
Umbilical Vein ◽  
Oral Anticoagulant Therapy ◽  
Marker Gene ◽  
Marker Genes ◽  
Type I

Direct oral anti-coagulants (DOACs) are employed in clinical practice for the prevention and treatment of recurrent venous thromboembolism and for the prevention of stroke in non-valvular atrial fibrillation. DOACs directly and reversibly inhibit activated factor X or thrombin and can interfere with other pathophysiological processes such as inflammation, lipid metabolism, and bone turnover. We aimed to evaluate the possible effects of DOACs on osteogenesis and angiogenesis. We treated 34 patients affected by cardiovascular disorders with DOACs; biochemical and molecular analyses were performed before and after three months of treatment. Circulating progenitors (CPs; CD34−, CD45−, CD14−, CD73+, CD105+), which share typical bone marrow stem cell (MSCs) features, were harvested from peripheral blood of the study subjects to monitor the expression of osteogenesis-related genes RUNX2 and SPARC. Human umbilical vein endothelial cells (HUVECs) were used to probe angiogenesis-related VEGF, CD31, and CD105 gene expression. We performed co-culture experiments using a commercial human mesenchymal stem cells line (hMSCs) obtained from bone marrow and HUVECs. Clinical parameters related to bone metabolism, coagulation, renal and liver function, and the lipid profile were evaluated. Values of the C-terminal telopeptide type I collagen (CTX) increased after the treatment. We found a significant increase in osteogenesis marker gene expression in CPs after three months of anticoagulant therapy. An increase in the RUNX2 expression determinant alone was detected instead in hMSCs co-cultured with HUVECs in the presence of treated patients’ sera. The VEGF, CD31, and CD105 marker genes appeared to be significantly upregulated in HUVECs co-cultured with hMSCs in the presence of treated patients’ sera. Under these conditions, new vessel formation increased as well. Our results highlight an unexpected influence of DOAC therapy on osteogenic commitment and vascular endothelial function promotion.

scholarly journals Transcriptional and Spatial Heterogeneity of Mouse Megakaryocytes at Single-Cell Resolution

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 275-275 ◽  
Author(s):  
Shu Sun ◽  
Chen Jin ◽  
Yueying Li ◽  
Jia Si ◽  
Yueli Cui ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Spatial Distribution ◽  
Stem Cell ◽  
Single Cell ◽  
Cell Population ◽  
Marker Genes ◽  
Specific Marker ◽  
Bone Marrow Niche ◽  
Hematopoietic Stem ◽  
High Ploidy

Megakaryocytes (MKs) have long been described solely as platelet progenitors. However, recent studies show that MKs also act as an essential component of the bone marrow niche to maintain hematopoietic stem cell function, and combat infection by engulfing and presenting antigens. However, it is not known whether these diverse programs are executed by a single cell population or distinct subsets of cells. We performed single-cell RNA sequencing (scRNA-seq) to dissect the heterogeneity of MKs. To overcome the difficulty in obtaining the rare (0.1% in BM) and oversized (up to 65μm) highly polyploid, fragile MKs, we developed an efficient isolation strategy by combining fluorescence-activated cell sorting (FACS) sorting, manual selection of highly viable cells, and FISH verification of ploidy. We obtained 920 CD41+ highly-purified, bone-marrow derived, murine MKs spanning each ploidy stages (2N-32N) for scRNA-seq with modified Smart-seq2 protocol. On average, we detected over 6800 expressed genes and 250,000 transcripts in each MK. All cells expressed classical markers such as Pf4 and Itga2b (CD41). Four cell clusters were identified using an unsupervised clustering method. Cells in Cluster 1 expressed mature MK markers CD42 and CD61, were enriched for hemostasis and platelet activation expression signatures, and consist of ≥8N cells, suggesting these MKs may represent platelet generating MKs. Cells in cluster 2 had lower CD42 and CD61 expression, were low ploidy (≤8N), and had higher expression of inflammation-related genes, including Ctss and Itgam ("inflammatory response-associated MKs"). Cells in Cluster 3 were enriched for DNA replication and DNA strand elongation (GO terms) and were in all ploidy stages ("MKs in polyploidization stage"). Cluster 4, most of which were high-ploidy, expressed high levels of CD42, CD61, TGF-β, and IGF1: factors regulating HSC behavior ("HSC niche cells"). Furthermore, we identified cell population-specific surface markers and transcription factors (TFs) for each of the 4 clusters. Then, immunostaining using antibodies against corresponding markers were performed to confirm the presence of respective MK subpopulations in the bone marrow. Our analyses suggest that defining MK stages by ploidy and traditional markers CD42 and CD61 alone may result in a genetically and developmentally heterogenous population of MK. Rather, MKs at various stages may be more specifically identified by these gene signatures. MKs with different functions are known to have specific spatial distribution in the bone marrow (BM) niche. To test whether MKs with distinct expression signatures are uniquely localized within BM, we performed immunofluorescence staining on BM sections using antibodies against cell population-specific marker genes. Remarkably, we observed that Cluster 1 cells directly contacted blood vessels while most of Cluster 4 cells resided within one cell diameter of HSCs. The unique spatial distribution of cluster 1 and 4 population are in consistency with their respective transcriptomic signatures, and support that platelet generation and HSC maintenance are carried out by two distinct MK subpopulations. We further investigated the potential intrinsic relationship of these four Clusters during megakaryopoiesis. Developmental time courses were reconstructed using Monocle analysis, demonstrating that polyploidization (Cluster 3) occurs at the early stage of MK development with subsequent differentiation toward three orientations. While MKs with low ploidy appear to have two distinct cell fates (immuno-modulation or polyploidization), MKs with high ploidy (≥8N) differentiate towards populations associated with platelet production or stem cell regulation. In summary, our study provides the first in vivo transcriptomic profile of megakaryopoiesis and a potential map of megakaryocyte heterogeneity at the single-cell resolution. MKs may be classified into different functional subpopulations irrespective to their developmental stage and degree of ploidy. These observations suggest that megakaryopoiesis does not occur merely in a stepwise process, but is dynamic and adaptive to locations in the BM and biological needs. Disclosures No relevant conflicts of interest to declare.

scholarly journals Fermented Oyster Extract Promotes Osteoblast Differentiation by Activating the Wnt/β-Catenin Signaling Pathway, Leading to Bone Formation

Biomolecules ◽  
2019 ◽  
Vol 9 (11) ◽  
pp. 711 ◽  
Author(s):  
Ilandarage Menu Neelaka Molagoda ◽  
Wisurumuni Arachchilage Hasitha Maduranga Karunarathne ◽  
Yung Hyun Choi ◽  
Eui Kyun Park ◽  
You-Jin Jeon ◽  
...  
Keyword(s):  
Beneficial Effect ◽  
Nuclear Translocation ◽  
Bone Mineralization ◽  
Bone Morphogenetic Protein 2 ◽  
Marker Genes ◽  
Mitochondrial Activity ◽  
Specific Marker ◽  
Type I ◽  
Zebrafish Larvae ◽  
Alp Activity

The Pacific oyster, Crassostrea gigas, is well-known as a nutritious food. Recently, we revealed that fermented extract of C. gigas (FO) inhibited ovariectomy-induced osteoporosis, resulting from suppression of osteoclastogenesis. However, since the beneficial effect of FO on osteogenesis is poorly understood, it was examined in mouse preosteoblast MC3T3-E1 cells, human osteosarcoma MG-63 osteoblast-like cells, and zebrafish larvae in this study. We found that FO increased mitochondrial activity from days 1 to 7; however, total cell number of MC3T3-E1 cells gradually decreased without any change in cell viability, which suggests that FO stimulates the differentiation of MC3T3-E1 cells. FO also promoted the expression of osteoblast marker genes, including runt-related transcription factor 2 (mRUNX2), alkaline phosphatase (mALP), collagen type I α1 (mCol1α1), osteocalcin (mOCN), osterix (mOSX), bone morphogenetic protein 2 (mBMP2), and mBMP4 in MC3T3-E1 cells accompanied by a significant increase in ALP activity. FO also increased nuclear translocation of RUNX2 and OSX transcription factors, ALP activity, and calcification in vitro along with the upregulated expression of osteoblast-specific marker proteins such as RUNX2, ALP, Col1α1, OCN, OSX, and BMP4. Additionally, FO enhanced bone mineralization (calcein intensity) in zebrafish larvae at 9 days post-fertilization comparable to that in the β-glycerophosphate (GP)-treated group. All the tested osteoblast marker genes, including zRUNX2a, zRUNX2b, zALP, zCol1a1, zOCN, zBMP2, and zBMP4, were also remarkably upregulated in the zebrafish larvae in response to FO. It also promoted tail fin regeneration in adult zebrafish as same as the GP-treated groups. Furthermore, not only FO positively regulate β-catenin expression and Wnt/β-catenin luciferase activity, but pretreatment with a Wnt/β-catenin inhibitor (FH535) also significantly decreased FO-mediated bone mineralization in zebrafish larvae, which indicates that FO-induced osteogenesis depends on the Wnt/β-catenin pathway. Altogether, the current study suggests that the supplemental intake of FO has a beneficial effect on osteogenesis.

scholarly journals Antiresorptive Therapy in Hyperthyroid Patients: Longitudinal Changes in Bone and Mineral Metabolism

1997 ◽  
Vol 82 (6) ◽  
pp. 1989-1994 ◽  
Author(s):  
Esteban Jódar ◽  
Manuel Muñoz-Torres ◽  
Fernando Escobar-Jiménez ◽  
Miguel Quesada ◽  
Juan D. Luna ◽  
...  
Keyword(s):  
Bone Formation ◽  
Bone Mass ◽  
Type I ◽  
Antiresorptive Therapy ◽  
Mineral Density ◽  
Euthyroid State ◽  
Bone Formation Markers ◽  
Significant Difference ◽  
Hyperthyroid Patients

Abstract The effect of antiresorptive therapy with nasal calcitonin (CT) in recently diagnosed hyperthyroid patients on conventional medical therapy as well as the evolution of bone metabolism were assessed. Forty-five patients with recent-onset hyperthyroidism (<12 weeks) were sex and menopause stratified and randomly allocated to treatment with carbimazole (Neotomizol), carbimazole plus low dose CT (Calsynar; 100 IU/day, 2 days/week), or carbimazole plus high dose CT (Calsynar; 100 IU/day, 14 days/month). Bone mineral density was measured by dual x-ray absorptiometry in lumbar spine, femoral neck, and Ward’s triangle at 0, 9, and 18 months of treatment. We also determined free T4, free T3, TSH, osteocalcin, total and bone alkaline phosphatases, tartrate-resistant acid phosphatase, type I collagen C telopeptide, and urinary hydroxyproline every 3 months of follow-up. No significant difference was observed among treatments. A euthyroid state was attained at 3 months. Bone mass increased significantly at the 9 month evaluation (P < 0.05), with a 5–10% net gain during follow-up. Nevertheless, final bone mass was 4–8% smaller than expected. Bone formation markers were increased at 0 and 3 months, with reductions at 6–9 months; resorption bone markers showed a significant reduction at the 3 month evaluation. These results indicate that the euthyroid state partially reduces hyperthyroidism-associated osteopenia, with a bone mass recovery period during the 6–9 early months of effective treatment. This recovery phase is characterized by raised bone formation markers and reduced bone resorption markers. The treatment with nasal CT at the doses assayed has no additional effect over that of attainment of the euthyroid state.

scholarly journals Type I Interferon α/β Receptor-Mediated Signaling Negatively Regulates Antiviral Cytokine Responses in Murine Bone-Marrow-Derived Mast Cells and Protects the Cells from Virus-Induced Cell Death

2020 ◽  
Vol 21 (23) ◽  
pp. 9041
Author(s):  
Maedeh Darzianiazizi ◽  
Yeganeh Mehrani ◽  
Lily Chan ◽  
Robert C. Mould ◽  
Raveendra R. Kulkarni ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Mast Cells ◽  
Inflammatory Cytokines ◽  
Inflammatory Responses ◽  
Type I Interferons ◽  
Interferon Α ◽  
Type I ◽  
Intact Cells ◽  
Cytokine Responses

Mast cells (MCs) are critical for initiating inflammatory responses to pathogens including viruses. Type I interferons (IFNs) that exert their antiviral functions by interacting with the type I IFN receptor (IFNAR) play a central role in host cellular responses to viruses. Given that virus-induced excessive toxic inflammatory responses are associated with aberrant IFNAR signaling and considering MCs are an early source of inflammatory cytokines during viral infections, we sought to determine whether IFNAR signaling plays a role in antiviral cytokine responses of MCs. IFNAR-intact, IFNAR-blocked, and IFNAR-knockout (IFNAR−/−) bone-marrow-derived MCs (BMMCs) were treated in vitro with a recombinant vesicular stomatitis virus (rVSVΔm51) to assess cytokine production by these cells. All groups of MCs produced the cytokines interleukin-6 and tumor necrosis factor-α in response to rVSVΔm51. However, production of the cytokines was lowest in IFNAR-intact cells as compared with IFNAR−/− or IFNAR-blocked cells at 20 h post-stimulation. Surprisingly, rVSVΔm51 was capable of infecting BMMCs, but functional IFNAR signaling was able to protect these cells from virus-induced death. This study showed that BMMCs produced pro-inflammatory cytokines in response to rVSVΔm51 and that IFNAR signaling was required to down-modulate these responses and protect the cells from dying from viral infection.

scholarly journals Association between Visceral and Bone Marrow Adipose Tissue and Bone Quality in Sedentary and Physically Active Ovariectomized Wistar Rats

Life ◽  
2021 ◽  
Vol 11 (6) ◽  
pp. 478
Author(s):  
Hélder Fonseca ◽  
Andrea Bezerra ◽  
Ana Coelho ◽  
José Alberto Duarte
Keyword(s):  
Physical Activity ◽  
Bone Marrow ◽  
Adipose Tissue ◽  
Bone Mass ◽  
Bone Quality ◽  
Wistar Rats ◽  
Biomechanical Properties ◽  
Physically Active ◽  
Bone Formation Rate ◽  
Marrow Adiposity

Background: Obesity is considered protective for bone mass, but this view has been progressively challenged. Menopause is characterized by low bone mass and increased adiposity. Our aim was to determine how visceral and bone marrow adiposity change following ovariectomy (OVX), how they correlate with bone quality and if they are influenced by physical activity. Methods: Five-month-old Wistar rats were OVX or sham-operated and maintained in sedentary or physically active conditions for 9 months. Visceral and bone marrow adiposity as well as bone turnover, femur bone quality and biomechanical properties were assessed. Results: OVX resulted in higher weight, visceral and bone marrow adiposity. Visceral adiposity correlated inversely with femur Ct.Th (r = −0.63, p < 0.001), BV/TV (r = −0.67, p < 0.001), Tb.N (r = −0.69, p < 0.001) and positively with Tb.Sp (r = 0.58, p < 0.001). Bone marrow adiposity also correlated with bone resorption (r = 0.47, p < 0.01), bone formation rate (r = −0.63, p < 0.01), BV/TV (r = −0.85, p < 0.001), Ct.Th (r = −0.51, p < 0.0.01), and with higher empty osteocyte lacunae (r = 0.39, p < 0.05), higher percentage of osteocytes with oxidative stress (r = 0.64, p < 0.0.01) and lower femur maximal stress (r = −0.58, p < 0.001). Physical activity correlated inversely with both visceral (r = −0.74, p < 0.01) and bone marrow adiposity (r = −0.92, p < 0.001). Conclusions: OVX increases visceral and bone marrow adiposity which are associated with inferior bone quality and biomechanical properties. Physical activity could contribute to reduce adipose tissue and thereby improve bone quality.

scholarly journals scSorter: assigning cells to known cell types according to marker genes

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Hongyu Guo ◽  
Jun Li
Keyword(s):  
Real Data ◽  
Cell Types ◽  
Exact Expression ◽  
Marker Genes ◽  
Specific Marker ◽  
Sequencing Data ◽  
Reference Dataset ◽  
Over Expression ◽  
Higher Power ◽  
Cell Type Specific

AbstractOn single-cell RNA-sequencing data, we consider the problem of assigning cells to known cell types, assuming that the identities of cell-type-specific marker genes are given but their exact expression levels are unavailable, that is, without using a reference dataset. Based on an observation that the expected over-expression of marker genes is often absent in a nonnegligible proportion of cells, we develop a method called scSorter. scSorter allows marker genes to express at a low level and borrows information from the expression of non-marker genes. On both simulated and real data, scSorter shows much higher power compared to existing methods.

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