Mechanical loading intensities affect the release of extracellular vesicles from mouse bone marrow-derived hematopoietic progenitor cells and change their osteoclast-modulating effect

C. Bratengeier; L. Johansson; A. Liszka; A. D. Bakker; M. Hallbeck; A. Fahlgren

doi:10.1096/fj.202301520R

Mechanical loading intensities affect the release of extracellular vesicles from mouse bone marrow-derived hematopoietic progenitor cells and change their osteoclast-modulating effect

C. Bratengeier^*
, L. Johansson
, A. Liszka
, A. D. Bakker
, M. Hallbeck
, A. Fahlgren

^*Corresponding author for this work

Oral Cell Biology

Research output: Contribution to Journal › Article › Academic › peer-review

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-Β 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 (10 000× g) obtained after low-intensity loading and induced by exosomes (100 000× 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.

Original language	English
Article number	e23323
Pages (from-to)	1-20
Number of pages	20
Journal	FASEB Journal
Volume	38
Issue number	1
Early online date	28 Nov 2023
DOIs	https://doi.org/10.1096/fj.202301520R
Publication status	Published - Jan 2024

Bibliographical note

Funding Information:
The authors thank Dr. Maria Ntzouni at the Core Facility at the Faculty of Medicine and Health Sciences, Linköping University for the preparation and analysis of EV samples by Transmission Electron Microscopy and Andrew Hossein Ordoubadian at Accent Language Service, Sweden for the help with proofreading and editing the manuscript. We also would like to thank the core facility at NEO, BEA, Bioinformatics and Expression Analysis, which is supported by the board of research at the Karolinska Institute and the research committee at the Karolinska Hospital.

Funding Information:
This research was supported by the Swedish Research Council (Vetenskapsrådet, 2016‐01822, 2019‐01016, and 2019‐03636) and the County Council of Östergötland.

Funding Information:
The authors thank Dr. Maria Ntzouni at the Core Facility at the Faculty of Medicine and Health Sciences, Linköping University for the preparation and analysis of EV samples by Transmission Electron Microscopy and Andrew Hossein Ordoubadian at Accent Language Service, Sweden for the help with proofreading and editing the manuscript. We also would like to thank the core facility at NEO, BEA, Bioinformatics and Expression Analysis, which is supported by the board of research at the Karolinska Institute and the research committee at the Karolinska Hospital.

Publisher Copyright:
© 2023 The Authors. The FASEB Journal published by Wiley Periodicals LLC on behalf of Federation of American Societies for Experimental Biology.

Funding

The authors thank Dr. Maria Ntzouni at the Core Facility at the Faculty of Medicine and Health Sciences, Linköping University for the preparation and analysis of EV samples by Transmission Electron Microscopy and Andrew Hossein Ordoubadian at Accent Language Service, Sweden for the help with proofreading and editing the manuscript. We also would like to thank the core facility at NEO, BEA, Bioinformatics and Expression Analysis, which is supported by the board of research at the Karolinska Institute and the research committee at the Karolinska Hospital. This research was supported by the Swedish Research Council (Vetenskapsrådet, 2016‐01822, 2019‐01016, and 2019‐03636) and the County Council of Östergötland. The authors thank Dr. Maria Ntzouni at the Core Facility at the Faculty of Medicine and Health Sciences, Linköping University for the preparation and analysis of EV samples by Transmission Electron Microscopy and Andrew Hossein Ordoubadian at Accent Language Service, Sweden for the help with proofreading and editing the manuscript. We also would like to thank the core facility at NEO, BEA, Bioinformatics and Expression Analysis, which is supported by the board of research at the Karolinska Institute and the research committee at the Karolinska Hospital.

Funders	Funder number
Karolinska Hospital
Faculté de médecine et des sciences de la santé, Université de Sherbrooke
Länsstyrelsen Östergötland
Linköpings Universitet
Karolinska Institutet
Vetenskapsrådet	2016‐01822, 2019‐03636, 2019‐01016
Vetenskapsrådet

Keywords

aseptic loosening
calpeptin
exosomes
fluid shear stress
GW4869
microvesicles

Access to Document

10.1096/fj.202301520R

Persistent URL (handle)

Persistent link

Cite this

@article{6ba5e2d2beb742d9aa6f5d2680375634,

title = "Mechanical loading intensities affect the release of extracellular vesicles from mouse bone marrow-derived hematopoietic progenitor cells and change their osteoclast-modulating effect",

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-Β 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 (10 000× g) obtained after low-intensity loading and induced by exosomes (100 000× 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.",

keywords = "aseptic loosening, calpeptin, exosomes, fluid shear stress, GW4869, microvesicles",

author = "C. Bratengeier and L. Johansson and A. Liszka and Bakker, \{A. D.\} and M. Hallbeck and A. Fahlgren",

note = "Funding Information: The authors thank Dr. Maria Ntzouni at the Core Facility at the Faculty of Medicine and Health Sciences, Link{\"o}ping University for the preparation and analysis of EV samples by Transmission Electron Microscopy and Andrew Hossein Ordoubadian at Accent Language Service, Sweden for the help with proofreading and editing the manuscript. We also would like to thank the core facility at NEO, BEA, Bioinformatics and Expression Analysis, which is supported by the board of research at the Karolinska Institute and the research committee at the Karolinska Hospital. Funding Information: This research was supported by the Swedish Research Council (Vetenskapsr{\aa}det, 2016‐01822, 2019‐01016, and 2019‐03636) and the County Council of {\"O}sterg{\"o}tland. Funding Information: The authors thank Dr. Maria Ntzouni at the Core Facility at the Faculty of Medicine and Health Sciences, Link{\"o}ping University for the preparation and analysis of EV samples by Transmission Electron Microscopy and Andrew Hossein Ordoubadian at Accent Language Service, Sweden for the help with proofreading and editing the manuscript. We also would like to thank the core facility at NEO, BEA, Bioinformatics and Expression Analysis, which is supported by the board of research at the Karolinska Institute and the research committee at the Karolinska Hospital. Publisher Copyright: {\textcopyright} 2023 The Authors. The FASEB Journal published by Wiley Periodicals LLC on behalf of Federation of American Societies for Experimental Biology.",

year = "2024",

month = jan,

doi = "10.1096/fj.202301520R",

language = "English",

volume = "38",

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journal = "FASEB Journal",

issn = "0892-6638",

publisher = "John Wiley \& Sons Inc.",

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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. / Bratengeier, C.; Johansson, L.; Liszka, A. et al.
In: FASEB Journal, Vol. 38, No. 1, e23323, 01.2024, p. 1-20.

Research output: Contribution to Journal › Article › Academic › peer-review

TY - JOUR

T1 - Mechanical loading intensities affect the release of extracellular vesicles from mouse bone marrow-derived hematopoietic progenitor cells and change their osteoclast-modulating effect

AU - Bratengeier, C.

AU - Johansson, L.

AU - Liszka, A.

AU - Bakker, A. D.

AU - Hallbeck, M.

AU - Fahlgren, A.

N1 - Funding Information: The authors thank Dr. Maria Ntzouni at the Core Facility at the Faculty of Medicine and Health Sciences, Linköping University for the preparation and analysis of EV samples by Transmission Electron Microscopy and Andrew Hossein Ordoubadian at Accent Language Service, Sweden for the help with proofreading and editing the manuscript. We also would like to thank the core facility at NEO, BEA, Bioinformatics and Expression Analysis, which is supported by the board of research at the Karolinska Institute and the research committee at the Karolinska Hospital. Funding Information: This research was supported by the Swedish Research Council (Vetenskapsrådet, 2016‐01822, 2019‐01016, and 2019‐03636) and the County Council of Östergötland. Funding Information: The authors thank Dr. Maria Ntzouni at the Core Facility at the Faculty of Medicine and Health Sciences, Linköping University for the preparation and analysis of EV samples by Transmission Electron Microscopy and Andrew Hossein Ordoubadian at Accent Language Service, Sweden for the help with proofreading and editing the manuscript. We also would like to thank the core facility at NEO, BEA, Bioinformatics and Expression Analysis, which is supported by the board of research at the Karolinska Institute and the research committee at the Karolinska Hospital. Publisher Copyright: © 2023 The Authors. The FASEB Journal published by Wiley Periodicals LLC on behalf of Federation of American Societies for Experimental Biology.

PY - 2024/1

Y1 - 2024/1

N2 - 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-Β 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 (10 000× g) obtained after low-intensity loading and induced by exosomes (100 000× 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.

AB - 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-Β 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 (10 000× g) obtained after low-intensity loading and induced by exosomes (100 000× 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.

KW - aseptic loosening

KW - calpeptin

KW - exosomes

KW - fluid shear stress

KW - GW4869

KW - microvesicles

UR - https://www.scopus.com/pages/publications/85177760726

UR - https://www.scopus.com/pages/publications/85177760726#tab=citedBy

U2 - 10.1096/fj.202301520R

DO - 10.1096/fj.202301520R

M3 - Article

C2 - 38015031

AN - SCOPUS:85177760726

SN - 0892-6638

VL - 38

SP - 1

EP - 20

JO - FASEB Journal

JF - FASEB Journal

IS - 1

M1 - e23323

ER -

Mechanical loading intensities affect the release of extracellular vesicles from mouse bone marrow-derived hematopoietic progenitor cells and change their osteoclast-modulating effect

Abstract

Bibliographical note

Funding

Keywords

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