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At least 1,333 records · Page 74

Advanced Fuel Cell System Thermal Management for NASA Exploration Missions

The NASA Glenn Research Center is developing advanced passive thermal management technology to reduce the mass and improve the reliability of space fuel cell systems for the NASA exploration program. An analysis of a state-of-the-art fuel cell cooling systems was done to benchmark the portion of a fuel cell system s mass that is dedicated to thermal management. Additional analysis was done to determine the key performance targets of the advanced passive thermal management technology that would substantially reduce fuel cell system mass.

Burke, Kenneth A.↗

Carbon nanotube supported PdAg nanoparticles for electrocatalytic oxidation of glycerol in anion exchange membrane fuel cells

Electro-oxidation of alcohol is the key reaction occurring at the anode of a direct alcohol fuel cell (DAFC), in which both reaction kinetics (rate) and selectivity (to deep oxidation products) need improvement to obtain higher power density and fuel utilization for a more efficient DAFC. We recently found that a PdAg bimetallic nanoparticle catalyst is more efficient than Pd for alcohol oxidation: Pd can facilitate deprotonation of alcohol in a base electrolyte, while Ag can promote intermediate aldehyde oxidation and cleavage of C-single bondC bond of C 3 species to C 2 species. Furthermore, a combination of the two active sites (Pd and Ag) with two different functions, can simultaneously improve the reaction rates and deeper oxidation products of alcohols. In this continuing work, Pd, Ag mono, and bimetallic nanoparticles supported on carbon nanotubes (Ag/CNT, Pd/CNT, Pd 1 Ag 1 /CNT, and Pd 1 Ag 3 /CNT) were prepared using an aqueous-phase reduction method; they served as working catalysts for studying electrocatalytic oxidation of glycerol in an anion-exchange membrane-based direct glycerol fuel cell. Combined XRD, TEM, and HAADF-STEM analyses performed to fully characterize as-prepared catalysts suggested that they have small particle sizes: 2.0 nm for Pd/CNT, 2.3 nm for PdAg/CNT, 2.4 nm for PdAg 3 /CNT, and 13.9 nm for Ag/CNT. XPS further shows that alloying with Ag results in more metal state Pd presented on the surface, and this may be related to their higher direct glycerol fuel cell (DGFC) performances. Single DGFC performance and product analysis results show that PdAg bimetallic nanoparticles can not only improve the glycerol reaction rate so that higher power output can be achieved, but also facilitate deep oxidation of glycerol so that a higher faradaic efficiency and fuel utilization can be achieved along with optimal reaction conditions (increased base-to-fuel ratio). Half-cell electrocatalytic activity measurement and single fuel cell product analysis of different glycerol oxidation intermediates, including C 3 : glycerate, tartronate, mesoxalate, and lactate; C 2 : glycolate and oxalate, over PdAg/CNT catalyst was further conducted and produced deeper insight into the synergistic effects and reaction pathways of bimetallic PdAg catalysts in glycerol electrocatalytic oxidation.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗

Exogenous hydrogen sulfide promotes cell proliferation and differentiation by modulating autophagy in human keratinocytes

The effects and the underlying mechanisms of hydrogen sulfide (H{sub 2}S) on keratinocyte proliferation and differentiation are still less known. In the current study, we investigated the effects and the underlying mechanisms of exogenous H{sub 2}S on keratinocyte proliferation and differentiation. Human keratinocytes (HaCaT cells) were treated with various concentrations (0.05, 0.25, 0.5 and 1 mM) of sodium hydrosulfide (NaHS, a donor of H{sub 2}S) for 24 h. A CCK-8 assay was used to assess cell viability. Western blot analysis was performed to determine the expression levels of proteins associated with differentiation and autophagy. Transmission electron microscopy was performed to observe autophagic vacuoles, and flow cytometry was applied to evaluate apoptosis. NaHS promoted the viability, induced the differentiation, and enhanced autophagic activity in a dose-dependent manner in HaCaT cells but had no effect on cell apoptosis. Blockage of autophagy by ATG5 siRNA inhibited NaHS-induced cell proliferation and differentiation. The current study demonstrated that autophagy in response to exogenous H{sub 2}S treatment promoted keratinocyte proliferation and differentiation. Our results provide additional insights into the potential role of autophagy in keratinocyte proliferation and differentiation. - Highlights: • Exogenous H{sub 2}S promotes keratinocyte proliferation and differentiation. • The effects of H{sub 2}S on proliferation and differentiation is modulated by autophagy. • Exogenous H{sub 2}S has no effect on keratinocyte apoptosis.

60 APPLIED LIFE SCIENCES↗

Implications of Pathologic Complete Response Beyond Mediastinal Nodal Clearance With High-Dose Neoadjuvant Chemoradiation Therapy in Locally Advanced, Non-Small Cell Lung Cancer

To determine, in a retrospective analysis of a large cohort of stage III non-small cell lung cancer patients treated with curative intent at our institution, whether having a pathologic complete response (pCR) influenced overall survival (OS) or freedom from recurrence (FFR) in patients who underwent definitive (≥60 Gy) neoadjuvant doses of chemoradiation (CRT).

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Development of complex-shaped liver multicellular spheroids as a human-based model for nanoparticle toxicity assessment in vitro

The emergence of human-based models is incontestably required for the study of complex physiological pathways and validation of reliable in vitro methods as alternative for in vivo studies in experimental animals for toxicity assessment. With this objective, we have developed and tested three dimensional environments for cells using different types of hydrogels including transglutaminase-cross-linked gelatin, collagen type I, and growth-factor depleted Matrigel. Cells grown in Matrigel exhibited the greatest cell proliferation and spheroid diameter. Moreover, analysis of urea and albumin biosynthesis revealed that the created system allowed the immortalized liver cell line HepG2 to re-establish normal hepatocyte-like properties which were not observed under the conditions of conventional cell cultures. This study presents a scalable technology for production of complex-shaped liver multicellular spheroids as a system which improves the predictive value of cell-based assays for safety and risk assessment. The time- and dose-dependent toxicity of nanoparticles demonstrates a higher cytotoxic effect when HepG2 cells grown as monolayer than embedded in hydrogels. The experimental setup provided evidence that the cell environment has significant influence on cell sensitivity and that liver spheroid is a useful and novel tool to examine nanoparticle dosing effect even at the level of in vitro studies. Therefore, this system can be applied to a wide variety of potentially hostile compounds in basic screening to provide initial warning of adverse effects and trigger subsequent analysis and remedial actions. - Highlights: • Comparison of HepG2 cells growth in Matrigel, Collagen I gel and gelatin gel. • Examination of nanoparticles (NP) dosing effect at the level of in vitro studies. • Influence of the cell culture media composition on the cytotoxic effect of NP.

60 APPLIED LIFE SCIENCES↗

The role of hepatocyte nuclear factor 4-alpha in perfluorooctanoic acid- and perfluorooctanesulfonic acid-induced hepatocellular dysfunction

Perfluorooctanoic acid (PFOA) and perfluorooctanesulfonic acid (PFOS), chemicals present in a multitude of consumer products, are persistent organic pollutants. Both compounds induce hepatotoxic effects in rodents, including steatosis, hepatomegaly and liver cancer. The mechanisms of PFOA- and PFOS-induced hepatic dysfunction are not completely understood. We present evidence that PFOA and PFOS induce their hepatic effects via targeting hepatocyte nuclear factor 4-alpha (HNF4α). Human hepatocytes treated with PFOA and PFOS at a concentration relevant to occupational exposure caused a decrease in HNF4α protein without affecting HNF4α mRNA or causing cell death. RNA sequencing analysis combined with Ingenuity Pathway Analysis of global gene expression changes in human hepatocytes treated with PFOA or PFOS indicated alterations in the expression of genes involved in lipid metabolism and tumorigenesis, several of which are regulated by HNF4α. Further investigation of specific HNF4α target gene expression revealed that PFOA and PFOS could promote cellular dedifferentiation and increase cell proliferation by down regulating positive targets (differentiation genes such as CYP7A1) and inducing negative targets of HNF4α (pro-mitogenic genes such as CCND1). Furthermore, in silico docking simulations indicated that PFOA and PFOS could directly interact with HNF4α in a similar manner to endogenous fatty acids. Collectively, these results highlight HNF4α degradation as novel mechanism of PFOA and PFOS-mediated steatosis and tumorigenesis in human livers. - Highlights: • PFOA and PFOS cause decreased HNF4α protein expression in human hepatocytes. • PFOA and PFOS promote changes associated with lipid metabolism and carcinogenesis. • PFOA and PFOS induced changes in gene expression associated with cellular dedifferentiation. • PFOA and PFOS induce expression of Nanog, a transcription factor involved in stem cell development.

60 APPLIED LIFE SCIENCES↗

Quantification of glioblastoma progression in zebrafish xenografts: Adhesion to laminin alpha 5 promotes glioblastoma microtumor formation and inhibits cell invasion

Highlights: • Developed an embryo-larval zebrafish model to study GBM progression. • Quantitatively measured GBM BV association, invasion and microtumor formation. • Laminin alpha 5 decreases U251MG dispersal and increases microtumors. • Microenvironmental laminin alpha 5 slows U251MG cell invasion in vivo. Glioblastoma (GBM) is a deadly disease due to its ability to quickly invade and destroy brain tissue. Slowing or stopping GBM cell progression is crucial to help those inflicted with the disease. Our lab created an embryo-larval zebrafish xenograft model as a tool to study human GBM progression in an observable brain environment. The zebrafish brain is a dynamic and complex environment providing an optimal setting for studying GBM cell progression. Here we demonstrate the ability of our model to quantitate GBM proliferation, dispersal, blood vessel association, microtumor formation, and individual cell invasion by evaluating the importance of an extracellular matrix protein, laminin alpha 5 (lama5), on U251MG cell progression. Lama5 has been implicated in cancer cell survival, proliferation and invasion and is a known adhesion site for GBM cells. While lama5 is highly expressed in endothelial cells in the brain, it is unknown how lama5 affects GBM behavior. Using a lama5 morpholino, we discovered that lama5 decreased U251MG dispersal by 23% and doubles the formation of blood vessel dependent microtumors. Despite lama5 being a known attachment site for GBM, lama5 expression had no effect on U251MG association with blood vessels. Analysis of individual U251MG cells revealed lama5 significantly lowered invasion as mobile U251MG cells traveled 32.5 μm less, invaded 5.0 μm/hr slower and initiated invasion 60% few times per cell.

60 APPLIED LIFE SCIENCES↗

Determination of lattice parameters, strain state and composition in semipolar III-nitrides using high resolution X-ray diffraction

In group-III-nitride heterostructures with semipolar or nonpolar crystal orientation, anisotropic lattice and thermal mismatch with the buffer or substrate lead to a complex distortion of the unit cells, e.g., by shearing of the lattice. This makes an accurate determination of lattice parameters, composition, and strain state under assumption of the hexagonal symmetry impossible. In this work, we present a procedure to accurately determine the lattice constants, strain state, and composition of semipolar heterostructures using high resolution X-ray diffraction. An analysis of the unit cell distortion shows that four independent lattice parameters are sufficient to describe this distortion. Assuming only small deviations from an ideal hexagonal structure, a linear expression for the interplanar distances d{sub hkl} is derived. It is used to determine the lattice parameters from high resolution X-ray diffraction 2ϑ-ω-scans of multiple on- and off-axis reflections via a weighted least-square fit. The strain and composition of ternary alloys are then evaluated by transforming the elastic parameters (using Hooke's law) from the natural crystal-fixed coordinate system to a layer-based system, given by the in-plane directions and the growth direction. We illustrate our procedure taking an example of (112{sup ¯}2) Al{sub κ}Ga{sub 1−κ}N epilayers with Al-contents over the entire composition range. We separately identify the in-plane and out-of-plane strains and discuss origins for the observed anisotropy.

71 CLASSICAL AND QUANTUM MECHANICS, GENERAL PHYSIC↗

A Techno-Economic Analysis and Cost Reduction Roadmap for III-V Solar Cells

III-V materials have achieved the highest efficiency of any solar cell technology. They have been commercially available since the 1960s, and have been widely used in space applications where high performance is required. However, prices of III-V solar cells are currently 2 to 3 orders of magnitude higher than other technologies, prohibiting their use in mainstream photovoltaic (PV) markets outside of high concentration photovoltaic systems. In this report, we present bottom-up cost models for current III-V solar cell technology, and explore the reasons behind these high costs. Then, we examine the advances required to drive cost down, and present a roadmap illustrating potential pathways to reach costs that could enable III-Vs to be competitive in broader, terrestrial markets without concentration. We find that cell manufacturing costs of $0.40/W or below could be achieved in high volume production, but that this would require commercialization and scale-up of a low-cost epitaxial growth technique, implementation of alternative, low-cost metallization schemes, and, critically, significant research and development to address the high cost of the substrate.

14 SOLAR ENERGY↗

The implications of fast charge in lithium ion battery performance and life: cell vs. pack

This study investigates the effect of 50-kW (about 2C) direct current fast charging on a full-size battery electric vehicle's battery pack in comparison to a pack exclusively charged at 3.3?kW, which is the common alternating current Level 2 charging power level. Comparable scaled charging protocols are also independently applied to individual cells at three different temperatures, 20?°C, 30?°C, and 40?°C, to perform a comparative analysis with the packs. Dominant cell-level aging modes were identified through incremental capacity analysis and compared with full packs to gain a clear understanding of additional key factors that affect pack aging. While the cell-level study showed a minor impact on performance due to direct current fast charging, the packs showed a significantly higher rate of capacity fade under similar charging protocols. This indicates that pack-level aging cannot be directly extrapolated from cell evaluation. Delayed fast charging, completing shortly before discharge, was found to have less of an impact on battery degradation than conventional alternating current Level 2 charging.

25 ENERGY STORAGE↗

Enterococcus faecalis immunoregulates osteoclastogenesis of macrophages

Highlights: • An in vitro infection model of osteoclast precursors by E. faecalis was established. • E. faecalis infection upregulated the inflammatory response of osteoclast precursors. • E. faecalis infection attenuated RANKL-induced osteoclastogenesis of RAW264.7 cells. Persistent apical periodontitis (PAP) is characterized by refractory inflammation and progressive bone destruction. Enterococcus faecalis infection is considered an important etiological factor for the development of PAP, although the exact mechanisms remain unknown. This study aimed at investigating the role of E. faecalis in cell proliferation, inflammatory reactions and osteoclast differentiation of macrophages using an in vitro infection model of osteoclast precursor RAW264.7 cells. A cell viability assay of cultured RAW264.7 cells exposed to live E. faecalis at a multiplicity of infection of 100 for 2 h, indicated that the infection exhibited no cytotoxic effect. Transmission electron microscopy images revealed no apoptotic changes but a rise of metabolic activity and phagocytic features in the infected RAW264.7 cells. Confocal laser scanning microscopic and flow cytometric analysis indicated that the phagocytosis of RAW264.7 cells was activated by E. faecalis infection. Furthermore, quantitative real-time PCR assays demonstrated that the expression of inflammatory cytokines was remarkably elevated in infected RAW264.7 cells. Differentiation of infected RAW264.7 cells into osteoclasts was remarkably attenuated, and expression of osteoclast marker genes as well as fusogenic genes significantly dropped. In summary, E. faecalis appears to attenuate osteoclastic differentiation of RAW264.7 precursor cells, rather stimulates them to function as macrophages.

60 APPLIED LIFE SCIENCES↗

National Cancer Institute Think-Tank Meeting Report on Proteomic Cartography and Biomarkers at the Single-Cell Level: Interrogation of Premalignant Lesions

A Think-Tank Meeting was convened by the National Cancer Institute (NCI) to solicit experts’ opinion on the development and application of multi-omic single-cell analyses, and especially single-cell proteomics, to improve the development of a new generation of biomarkers for cancer risk, early detection, diagnosis, prognosis as well as to discuss the discovery of new targets for prevention and therapy. It is anticipated that such markers and targets will be based on cellular, subcellular, molecular and functional aberrations within the lesion and within individual cells. Additionally, single-cell proteomic data will be essential for the establishment of new tools that with searchable and scalable features that include spatial and temporal cartographies of premalignant and malignant lesions. Challenges and potential solutions that were discussed included: • The best way/s to analyze single-cells from fresh and preserved tissue • Detection and analysis of secreted molecules and from single cells, especially from a tissue slice • Detection of new, previously undocumented cell type/s in the premalignant and early stage cancer tissue microenvironment • Multi-omic integration of data to support and inform proteomic measurements • Subcellular organelles – identifying abnormal structure, function, distribution and location within individual premalignant and malignant cells • How to improve the dynamic range of single-cell proteomic measurements for discovery of differentially expressed proteins and their post translational modifications (PTM) • The depth of coverage measured concurrently using single-cell techniques • Quantitation - absolute or semiquantitative? • Single methodology or multiplexed combinations? • Application of analytical methods for identification of biologically significant subsets • Data visualization of N-dimensional datasets • How to construct intercellular signaling networks in individual cells within premalignant tumor microenvironments (TME) • Associations between intrinsic cellular processes and extrinsic stimuli • How to predict cellular responses to stress inducing stimuli • Identification of new markers for prediction of progression from precursor, benign and localized lesions to invasive cancer, based on spatial and temporal changes within individual cells • Identification of new targets for immunoprevention or immunotherapy – identification of neoantigens and surfactome of individual cells within a lesion

59 BASIC BIOLOGICAL SCIENCES↗

Design and Analysis of the Staggered Double Grating Slow Wave Circuit for 263 GHz Sheet Beam TWT

The complete design process of a high-frequency circuit for a 263 GHz staggered double grating, sheet beam traveling wave tube is presented in this article. Here, this device, for use in a pulsed electron paramagnetic resonance spectrometer instrument, requires >30 dB gain and a 20 GHz bandwidth centered at 263 GHz. In addition to the standard Pierce gain analysis and point by point particle in cell (PIC) simulation, a novel fast pulse response analysis technique was utilized to determine the accurate synchronization voltage and test the ``hot” feature of the high-frequency circuit. Since this new method can evaluate the entire bandwidth in a single simulation, it can significantly reduce the computational resources normally required for the conventional PIC analysis while also illustrating the potential instabilities near the band edge. Good agreement between the fast pulse response and PIC simulation results validate the accuracy of this novel method. According to the analysis results and given the manufacturing limits of nano/micro-computer numerical control (CNC) machining, an appropriate SWS, coupler, and sever designs were chosen to complement the simulated design. Finally, a prototype circuit was manufactured and cold tested to verify the design and inspect the machining tolerances.

42 ENGINEERING↗

DCYTB is a predictor of outcome in breast cancer that functions via iron-independent mechanisms

Background: Duodenal cytochrome b (DCYTB) is a ferrireductase that functions together with divalent metal transporter 1 (DMT1) to mediate dietary iron reduction and uptake in the duodenum. DCYTB is also a member of a 16-gene iron regulatory gene signature (IRGS) that predicts metastasis-free survival in breast cancer patients. To better understand the relationship between DCYTB and breast cancer, we explored in detail the prognostic significance and molecular function of DCYTB in breast cancer. Methods: The prognostic significance of DCYTB expression was evaluated using publicly available microarray data. Signaling Pathway Impact Analysis (SPIA) of microarray data was used to identify potential novel functions of DCYTB. The role of DCYTB was assessed using immunohistochemistry and measurements of iron uptake, iron metabolism, and FAK signaling. Results: High DCYTB expression was associated with prolonged survival in two large independent cohorts, together totaling 1610 patients (cohort #1, p = 1.6e-11, n = 741; cohort #2, p = 1.2e-05, n = 869; log-rank test) as well as in the Gene expression-based Outcome for Breast cancer Online (GOBO) cohort (p < 1.0e-05, n = 1379). High DCYTB expression was also associated with increased survival in homogeneously treated groups of patients who received either tamoxifen or chemotherapy. Immunohistochemistry revealed that DCYTB is localized on the plasma membrane of breast epithelial cells, and that expression is dramatically reduced in high-grade tumors. Surprisingly, neither overexpression nor knockdown of DCYTB affected levels of ferritin H, transferrin receptor, labile iron or total cellular iron in breast cancer cells. Because SPIA pathway analysis of patient microarray data revealed an association between DCYTB and the focal adhesion pathway, we examined the influence of DCYTB on FAK activation in breast cancer cells. These experiments reveal that DCYTB reduces adhesion and activation of focal adhesion kinase (FAK) and its adapter protein paxillin. Conclusions: DCYTB is an important predictor of outcome and is associated with response to therapy in breast cancer patients. DCYTB does not affect intracellular iron in breast cancer cells. Instead, DCYTB may retard cancer progression by reducing activation of FAK, a kinase that plays a central role in tumor cell adhesion and metastasis.

60 APPLIED LIFE SCIENCES↗

Integrative epigenomic analysis reveals unique epigenetic signatures involved in unipotency of mouse female germline stem cells

Background: Germline stem cells play an essential role in establishing the fertility of an organism. Although extensively characterized, the regulatory mechanisms that govern the fundamental properties of mammalian female germline stem cells remain poorly understood. Results: We generate genome-wide profiles of the histone modifications H3K4me1, H3K27ac, H3K4me3, and H3K27me3, DNA methylation, and RNA polymerase II occupancy and perform transcriptome analysis in mouse female germline stem cells. Comparison of enhancer regions between embryonic stem cells and female germline stem cells identifies the lineage-specific enhancers involved in germline stem cell features. Additionally, our results indicate that DNA methylation primarily contributes to female germline stem cell unipotency by suppressing the somatic program and is potentially involved in maintenance of sexual identity when compared with male germline stem cells. Moreover, we demonstrate down-regulation of Prmt5 triggers differentiation and thus uncover a role for Prmt5 in maintaining the undifferentiated status of female germline stem cells. Conclusions: The genome-wide epigenetic signatures and the transcription regulators identified here provide an invaluable resource for understanding the fundamental features of mouse female germline stem cells.

59 BASIC BIOLOGICAL SCIENCES↗

Agkihpin, a novel SVAE may inhibit the migration and invasion of liver cancer cells associated with the inversion of EMT induced by Wnt/β-catenin signaling inhibition

In our previous work, agkihpin, a snake venom arginine esterase (SVAE), was isolated from the Gloydius halys Pallas, which could attenuate the migration of liver cancer cells. However, the mechanism of the effect of agkihpin on attenuating migration of liver cancer cell is unknown yet. Here, to learn more about agkihpin and explore the possibility of agkihpin as an anti-metastatic drug in the future, a series of experiments about the migration and invasion of liver cancer cells with agkihpin, HepG 2 and SMMC-7721, was conducted. Epithelial-mesenchymal transition (EMT) is an initial step and a major phenotype of cancer metastasis and invasion, while a number of EMT opposite phenomenons were observed, for example, epithelial marker E-cadherin was up-regulated, mesenchymal markers N-cadherin and Vimentin, and transcription regulators Snail and twist were down-regulated after treating with agkihpin in liver cancer cells; canonical Wnt/β-catenin pathway, one of the signals initiated EMT, was inhibited by decreased expressions of FZD7 and β-catenin, phosphorylation of GSK3β (Ser9), and nuclear β-catenin accumulation in agkihpin treated cancer cells. By using bioinformatics analysis and protease activity analysis in vitro we also found that agkihpin might bind and degrade FZD7. As a result, we hypothesized that agkihpin could inhibit the Wnt/β-catenin signaling pathway by cleaving FZD7, leading to the inactivation of the TCF/LEF transcription factor, which contributed to the inversion of EMT, and finally attenuated the migration and invasion of liver cancer cells. Therefore, our findings provided novel mechanistic insights into the role of SVAEs in liver cancer controlling, and raised the possibility that agkihpin may be used therapeutically in liver cancer. - Highlights: • We found for the first time that SVAE may inhibit the migration and invasion of liver cancer cells. • The inhibition of migration and invasion was associated with the inversion of EMT. • The inversion of EMT was induced by Wnt/β-catenin signaling inhibition.

60 APPLIED LIFE SCIENCES↗

Fusing Quantitative-Phase Imaging with Airy Light- Sheet Microscopy

We report the integration of quantitative-phase imaging (QPI) with light-sheet (LS) fluorescent microscopy on to a standard inverted microscope that retains compatibility with microfluidics. QPI enables label-free imaging and number-density quantification of single cells and their organelles. Conversely, LS yields considerable speed and phototoxicity gains in quantifying the 4D dynamics of gene-encoded fluorescent biomarkers. We will detail the system design that relied on spatial light interferometry for QPI and an accelerating Airy- beam light-sheet for fluorescence, its performance, as well as results of a representative multivariate imaging analysis of single-cell metabolism.

imaging, lattice light sheet, Yarrowia lipolytica,↗

Interleukin-3 plays dual roles in osteoclastogenesis by promoting the development of osteoclast progenitors but inhibiting the osteoclastogenic process

Highlights: •IL-3 treatment of bone marrow cells generates a population of hematopoietic cells. •IL-3-dependent hematopoietic cells are capable of differentiating into osteoclasts. •Osteoclasts derived from IL-3-dependent hematopoietic cells are functional. •IL-3 promotes the development of osteoclast progenitors. •IL-3 inhibits the osteoclastogenic process. -- Abstract: Interleukin (IL)-3, a multilineage hematopoietic growth factor, is implicated in the regulation of osteoclastogenesis. However, the role of IL-3 in osteoclastogenesis remains controversial; whereas early studies showed that IL-3 stimulates osteoclastogenesis, recent investigations demonstrated that IL-3 inhibits osteoclast formation. The objective of this work is to further address the role of IL-3 in osteoclastogenesis. We found that IL-3 treatment of bone marrow cells generated a population of cells capable of differentiating into osteoclasts in tissue culture dishes in response to the stimulation of the monocyte/macrophage-colony stimulating factor (M-CSF) and the receptor activator of nuclear factor kappa B ligand (RANKL). The IL-3-dependent hematopoietic cells were able to further proliferate and differentiate in response to M-CSF stimulation and the resulting cells were also capable of forming osteoclasts with M-CSF and RANKL treatment. Interestingly, IL-3 inhibits M-CSF-/RANKL-induced differentiation of the IL-3-dependent hematopoietic cells into osteoclasts. The flow cytometry analysis indicates that while IL-3 treatment of bone marrow cells slightly affected the percentage of osteoclast precursors in the surviving populations, it considerably increased the percentage of osteoclast precursors in the populations after subsequent M-CSF treatment. Moreover, osteoclasts derived from IL-3-dependent hematopoietic cells were fully functional. Thus, we conclude that IL-3 plays dual roles in osteoclastogenesis by promoting the development of osteoclast progenitors but inhibiting the osteoclastogenic process. These findings provide a better understanding of the role of IL-3 in osteoclastogenesis.

60 APPLIED LIFE SCIENCES↗