Acute hematopoietic stress in mice is followed by enhanced osteoclast maturation in the bone marrow microenvironment

Kuzmac, Sania; Grčević, Danka; Šućur, Alan; Ivčević, Sanja; Katavić, Vedran

doi:10.1016/j.exphem.2014.07.262

Cited by 8 publications

(5 citation statements)

References 65 publications

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“…Reduced SOD level in spleen was associated with the increased risk for cancer in rats 23 . When 10% of total blood of body is lost, the number of Sca-1(+) cells increased in the spleen of mice, which improved the hematopoietic function of the spleen 24 . Upregulating level of eNOS/NO attenuates the inflammatory response in spleen 25 .…”

Section: Discussionmentioning

confidence: 99%

Existence of multiple organ aging in animal model of emphysema induced by cigarette smoke extract

Liang¹,

He²,

Chen³

et al. 2022

Tob. Induc. Dis.

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INTRODUCTION It is commonly considered that COPD or at least emphysema represents accelerated lung aging induced in part by oxidative damage from cigarette smoke components. However, the issue if there are any aging signs in other organs in patients with COPD or emphysema remains unclear. The aim of this study is to explore whether there is multiple organ aging in the animal model of emphysema induced by cigarette smoke extract (CSE), and to ascertain the possible mechanisms, if any. METHODS The animal model of emphysema was induced by CSE. Histomorphological changes in lung, heart, liver, kidney and spleen tissues were measured after staining with hematoxylin and eosin (H&E). The concentrations of stem cell factor (SCF), CyclinD1 and superoxide dismutase (SOD) in serum were determined by ELISA kit. The expressions of p16 (INK4a), Sca-1, eNOS proteins and mRNA in lung, heart, liver, kidney and spleen tissues were detected by Western blotting and quantitative reverse transcriptase polymerase chain reaction (qRT-PCR), respectively. Decitabine (Dec) was applied to examine whether it could alter the changes caused by CSE. RESULTS The histomorphology of lung tissue was significantly changed, while other organs exhibited normal structure and histomorphology. The concentrations of SCF, CyclinD1 and SOD in serum were lower in the CSE group than in the control group. The expression levels of p16(INK4a) protein and mRNA in lung, heart, liver, kidney and spleen tissues were higher in the CSE group than in the control group, while the expression levels of Sca-1 and eNOS proteins and mRNA were lower in the CSE group than in the control group, in the tissues described above. Dec could partly alleviate the damages caused by CSE and the degree of alleviation resulted by Dec varied from organ to organ. CONCLUSIONS In addition to the aging of the lung tissue in the emphysema animal model induced by CSE, the tissues of the heart, liver, kidney and spleen were also in the progress of aging, but the sensibility and affinity of lung to CSE were higher than those of the other organs. Multiple organ aging may also exist in the animal model of emphysema induced by CSE. DEC can partly alleviate the multiple organ aging caused by CSE.

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Section: Discussionmentioning

confidence: 99%

Existence of multiple organ aging in animal model of emphysema induced by cigarette smoke extract

Liang¹,

He²,

Chen³

et al. 2022

Tob. Induc. Dis.

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“…We did not detect a high contribution of MkP-restricted HSPCs ( Carrelha et al, 2018 ; Sanjuan-Pla et al, 2013 ; Rodriguez-Fraticelli et al, 2018 ) to the MkP lineage ( Figure 3d ). Finally, as high EPO exposure has been linked to changes in macrophage numbers ( Theurl et al, 2016 ; Wang et al, 2018 ; Gilboa et al, 2017 ; Kuzmac et al, 2014 ; Ulyanova et al, 2016 ; Mausberg et al, 2011 ; Liao et al, 2018 ; Bretz et al, 2018 ), we analyzed the contribution of control and EPO-exposed HSPCs to the myeloid lineage in more detail, but could not detect changes in the percentage of the different myeloid subsets produced ( Figure 3—figure supplement 1a–c ).…”

Section: Resultsmentioning

confidence: 99%

“…Finally, as high EPO-exposure has been linked to changes in macrophage numbers [49][50][51][52][53][54][55][56] we analyzed the contribution of control and EPO-exposed HSPCs to the myeloid lineage in more detail, but could not detect changes in the percentage of the different myeloid subsets produced (Figure 3 figure supplement 1a-c).…”

Section: Contribution Of Me-and Mb-biased Hspcs To the DC And Mkp Lin...mentioning

confidence: 99%

Erythropoietin directly remodels the clonal composition of murine hematopoietic multipotent progenitor cells

Eisele

Cosgrove

Magniez

et al. 2022

eLife

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The cytokine erythropoietin (EPO) is a potent inducer of erythrocyte development and one of the most prescribed biopharmaceuticals. The action of EPO on erythroid progenitor cells is well established, but its direct action on hematopoietic stem and progenitor cells (HSPCs) is still debated. Here, using cellular barcoding, we traced the differentiation of hundreds of single murine HSPCs, after ex vivo EPO-exposure and transplantation, in five different hematopoietic cell lineages, and observed the transient occurrence of high-output Myeloid-Erythroid-megaKaryocyte (MEK)-biased and Myeloid-B-cell-Dendritic cell (MBDC)-biased clones. Single-cell RNA sequencing (ScRNAseq) analysis of ex vivo EPO-exposed HSPCs revealed that EPO induced the upregulation of erythroid associated genes in a subset of HSPCs, overlapping with multipotent progenitor (MPP) 1 and MPP2. Transplantation of Barcoded EPO-exposed-MPP2 confirmed their enrichment in Myeloid-Erythroid-biased clones. Collectively, our data show that EPO does act directly on MPP independent of the niche, and modulates fate by remodeling the clonal composition of the MPP pool.

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“…Cells were blocked with 0.5 µg of Fc block and stained with a viability marker. Cells were identified with the following markers: inflammatory monocytes: CD11b+, CD11c-, Ly6G-Ly6C int/hi+ ( 51 ); T cell inducers of osteoclasts: CD3+RANKL+; osteoclast precursors: CD11b -/low CD45+ckit+(CD117+) CD115+ ( 52 ); mesenchymal stem cells: CD45-CD29+CD105+ (R&D, Mesenchymal stem cell markers) ( Table S1 ). After staining, cells were washed and treated with a 1-step fix/lyse solution (eBioscience).…”

Section: Methodsmentioning

confidence: 99%

Inflammatory stimuli alter bone marrow composition and compromise bone health in the malnourished host

et al. 2022

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Inflammation has a role in the pathogenesis of childhood malnutrition. We investigated the effect of malnutrition and inflammatory challenge on bone marrow composition and bone health. We studied an established murine model of moderate acute malnutrition at baseline and after acute inflammatory challenge with bacterial lipopolysaccharide (LPS), a surrogate of Gram-negative bacterial sepsis, or Leishmania donovani, the cause of visceral leishmaniasis. Both of these infections cause significant morbidity and mortality in malnourished children. Of the 2 stimuli, LPS caused more pronounced bone marrow changes that were amplified in malnourished mice. LPS challenge led to increased inflammatory cytokine expression (Il1b, Il6, and Tnf), inflammasome activation, and inflammatory monocyte accumulation in the bone marrow of malnourished mice. Depletion of inflammatory monocytes in Csfr1-LysMcre-DT malnourished mice significantly reduced the inflammasome activation and IL1-ß production after LPS challenge. The inflammatory challenge also led to increased expansion of mesenchymal stem cells (MSCs), bone marrow adiposity, and expression of genes (Pparg, Adipoq, and Srbp1) associated with adipogenesis in malnourished mice. This suggests that inflammatory challenge promotes differentiation of BM MSCs toward the adipocyte lineage rather than toward bone-forming osteoblasts in the malnourished host. Concurrent with this reduced osteoblastic potential there was an increase in bone-resorbing osteoclasts, enhanced osteoclast activity, upregulation of inflammatory genes, and IL-1B involved in osteoclast differentiation and activation. The resulting weakened bone formation and increased bone resorption would contribute to the bone fragility associated with malnutrition. Lastly, we evaluated the effect of replacing lipid rich in omega-6 fatty acids (corn oil) with lipid-rich in omega-3 fatty acids (fish oil) in the nutrient-deficient diet. LPS-challenged malnourished mice that received dietary fish oil showed decreased expression of inflammatory cytokines and Rankl and reduced osteoclast differentiation and activation in the bone marrow. This work demonstrates that the negative effect of inflammatory challenge on bone marrow is amplified in the malnourished host. Increasing dietary intake of omega-3 fatty acids may be a means to reduce inflammation and improve bone health in malnourished children.

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Acute hematopoietic stress in mice is followed by enhanced osteoclast maturation in the bone marrow microenvironment

Cited by 8 publications

References 65 publications

Existence of multiple organ aging in animal model of emphysema induced by cigarette smoke extract

Existence of multiple organ aging in animal model of emphysema induced by cigarette smoke extract

Erythropoietin directly remodels the clonal composition of murine hematopoietic multipotent progenitor cells

Inflammatory stimuli alter bone marrow composition and compromise bone health in the malnourished host

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