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- Bratengeier, Cornelia, et al.
(författare)
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Mechanical loading intensities affect the release of extracellular vesicles from mouse bone marrow-derived hematopoietic progenitor cells and change their osteoclast-modulating effect
- 2024
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Ingår i: The FASEB Journal. - : WILEY. - 0892-6638 .- 1530-6860. ; 38:1
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Tidskriftsartikel (refereegranskat)abstract
- Low-intensity loading maintains or increases bone mass, whereas lack of mechanical loading and high-intensity loading decreases bone mass, possibly via the release of extracellular vesicles by mechanosensitive bone cells. How different loading intensities alter the biological effect of these vesicles is not fully understood. Dynamic fluid shear stress at low intensity (0.7 +/- 0.3 Pa, 5 Hz) or high intensity (2.9 +/- 0.2 Pa, 1 Hz) was used on mouse hematopoietic progenitor cells for 2 min in the presence or absence of chemical compounds that inhibit release or biogenesis of extracellular vesicles. We used a Receptor activator of nuclear factor kappa-Beta ligand-induced osteoclastogenesis assay to evaluate the biological effect of different fractions of extracellular vesicles obtained through centrifugation of medium from hematopoietic stem cells. Osteoclast formation was reduced by microvesicles (10 000x g) obtained after low-intensity loading and induced by exosomes (100 000x g) obtained after high-intensity loading. These osteoclast-modulating effects could be diminished or eliminated by depletion of extracellular vesicles from the conditioned medium, inhibition of general extracellular vesicle release, inhibition of microvesicle biogenesis (low intensity), inhibition of ESCRT-independent exosome biogenesis (high intensity), as well as by inhibition of dynamin-dependent vesicle uptake in osteoclast progenitor cells. Taken together, the intensity of mechanical loading affects the release of extracellular vesicles and change their osteoclast-modulating effect. The intensity of mechanical loading strongly affects bone remodeling by either formation of bone or resorption of bone. Low-intensity loading on bone cells releases microvesicles that reduce formation of bone-resorbing osteoclasts, while high-intensity loading on bone cells releases exosomes that induce formation of bone-resorbing osteoclasts. The graphical abstract was created with image
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- Christensen, J. B., et al.
(författare)
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Mapping initial and general recombination in scanning proton pencil beams
- 2020
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Ingår i: Physics in Medicine and Biology. - : IOP Publishing. - 0031-9155 .- 1361-6560. ; 65:11
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Tidskriftsartikel (refereegranskat)abstract
- The ion recombination is examined in parallel-plate ionization chambers in scanning proton beams at the Danish Centre for Particle Therapy and the Skandion Clinic. The recombination correction factor k(s) is investigated for clinically relevant energies between 70 MeV and 244 MeV for dose rates below 400 Gy min(-1) in air. The Boutillon formalism is used to separate the initial and general recombination. The general recombination is compared to predictions from the numerical recombination code IonTracks and the initial recombination to the Jaffe theory. k(s) is furthermore calculated with the two-voltage method (TVM) and extrapolation approaches, in particular the recently proposed three-voltage (3VL) method. The TVM is in agreement with the Boutillon method and IonTracks for dose rates above 100 Gy min(-1). However, the TVM calculated k(s) is closer related to the Jaffe theory for initial recombination for lower dose rate, indicating a limited application in scanning light ion beams. The 3VL is in turn found to generally be in agreement with Boutillon's method. The recombination is mapped as a function of the dose rate and proton energy at the two centres using the Boutillon formalism: the initial recombination parameter was found to be A = (0.10 +/- 0.01) V at DCPT and A = (0.22 +/- 0.13) V at Skandion, which is in better agreement with the Jaffe theory for initial recombination than previously reported values. The general recombination parameter was estimated to m2=(4.7 +/- 0.1).103V2nA-1cm-1m2=(7.2 +/- 0.1).103V2nA-1cm-1
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