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Published in: Osteoporosis International 7/2021

01-07-2021 | Original Article

Circulating MiR-21 expression is upregulated after 30 days of head-down tilt bed rest

Authors: D.A. Bemben, B.S. Baker, S.R. Buchanan, C.J. Ade

Published in: Osteoporosis International | Issue 7/2021

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Abstract

Summary

Relative expression of miR-21-5p in serum was upregulated in response to 30 days of bed rest, and miRNA fold changes were positively associated with serum calcium changes.

Introduction

Circulating miRNAs (c-miRNAs) have potential as biomarkers of cellular activity, and they may play a role in cell-to-cell communication. The purpose of this study was to examine c-miRNA and bone marker responses to a 30-day six-degree head-down bed rest protocol at an ambient 0.5% CO2.

Methods

Eleven participants (6 males/5 females, 25–50 years) had fasting blood draws taken 3 days before and immediately after completing the 30-day bed rest protocol at the Institute for Aerospace Medicine in Germany. Serum relative expression of miRNAs associated with bone function (miR-21-5p, -100-5p, -125b-5p, -126-3p) were analyzed using qPCR, and serum bone markers were quantitated using ELISA.

Results

Serum bone markers, sclerostin, and calcium significantly increased (p ≤ 0.036), and total hip aBMD significantly decreased (p = 0.003) post bed rest. Serum miR-21-5p relative expression was significantly upregulated (p = 0.018) post bed rest. Fold changes in miR-126-3p (r = 0.82, p = 0.002) and miR-21-5p (r = 0.62, p = 0.042) were positively correlated with absolute change in serum calcium. There were no sex differences in miRNA responses; women had greater percent increases in TRAP5b (37.3% vs. 16.9% p = 0.021) and greater percent decreases in total hip aBMD (− 2.15% vs. − 0.69%, p = 0.034) than men.

Conclusion

c-miR-21-5p has potential as a biomarker of bone resorption and bone loss in an unloading condition. The upregulation of miR-21-5p may reflect an increase in osteoclast activity after bed rest, which is corroborated by the increase in TRAP5b.
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Literature
1.
go back to reference LeBlanc A, Schneider V, Shackelford L, West S, Oganov V, Bakulin A, Voronin L (2000) Bone mineral and lean tissue loss after long duration spaceflight. J Musculoskelet Neuronal Interact 1:157–160PubMed LeBlanc A, Schneider V, Shackelford L, West S, Oganov V, Bakulin A, Voronin L (2000) Bone mineral and lean tissue loss after long duration spaceflight. J Musculoskelet Neuronal Interact 1:157–160PubMed
10.
go back to reference Kelch S, Balmayor ER, Seeliger C, Vester H, Kirschke JS, van Griensyen M (2017) miRNAs in bone tissue correlate to bone mineral density and circulating miRNAs are gender independent in osteoporotic patients. Sci Rep 7:15861. Published 2017 Nov 20. doi:https://doi.org/10.1038/s41598-017-16113-x Kelch S, Balmayor ER, Seeliger C, Vester H, Kirschke JS, van Griensyen M (2017) miRNAs in bone tissue correlate to bone mineral density and circulating miRNAs are gender independent in osteoporotic patients. Sci Rep 7:15861. Published 2017 Nov 20. doi:https://​doi.​org/​10.​1038/​s41598-017-16113-x
11.
go back to reference Feichtinger X, Muschitz C, Heimel P, Baierl A, Fahrleitner-Pammer A, Redl H, Resch H, Geiger E, Skalicky S, Dormann R, Plachel F, Pietschmann P, Grillari J, Hackl M, Kocijan R (2018) Bone-related circulating microRNAs miR-29b-3p, miR-550a-3p, and miR-324-3p and their association to bone microstructure and histomorphometry. Sci Rep 8:4867. Published 2018 Mar 20. doi:https://doi.org/10.1038/s41598-018-22844-2 Feichtinger X, Muschitz C, Heimel P, Baierl A, Fahrleitner-Pammer A, Redl H, Resch H, Geiger E, Skalicky S, Dormann R, Plachel F, Pietschmann P, Grillari J, Hackl M, Kocijan R (2018) Bone-related circulating microRNAs miR-29b-3p, miR-550a-3p, and miR-324-3p and their association to bone microstructure and histomorphometry. Sci Rep 8:4867. Published 2018 Mar 20. doi:https://​doi.​org/​10.​1038/​s41598-018-22844-2
13.
go back to reference Alsani S, Abhari A, Sakhinia E, Sanajou D, Rajabi H, Rahimzadeh S (2019) Interplay between microRNAs and Wnt, transforming growth factor-β, and bone morphogenic protein signaling pathways promote osteoblastic differentiation of mesenchymal stem cells. J Cell Physiol 234:8082–8093. https://doi.org/10.1002/jcp.27582CrossRef Alsani S, Abhari A, Sakhinia E, Sanajou D, Rajabi H, Rahimzadeh S (2019) Interplay between microRNAs and Wnt, transforming growth factor-β, and bone morphogenic protein signaling pathways promote osteoblastic differentiation of mesenchymal stem cells. J Cell Physiol 234:8082–8093. https://​doi.​org/​10.​1002/​jcp.​27582CrossRef
18.
go back to reference Valenti MT, Deiana M, Cheri S, Dotta M, Zamboni F, Gabbiani D, Schena F, Carbonare LD, Mottes M. (2019) Physical exercise modulates miR-21-5p, miR-129-5p, miR-378-5p, and miR-188-5p expression in progenitor cells promoting osteogenesis, Cells 8:742. Published 2019 Jul 19. doi:https://doi.org/10.3390/cells8070742 Valenti MT, Deiana M, Cheri S, Dotta M, Zamboni F, Gabbiani D, Schena F, Carbonare LD, Mottes M. (2019) Physical exercise modulates miR-21-5p, miR-129-5p, miR-378-5p, and miR-188-5p expression in progenitor cells promoting osteogenesis, Cells 8:742. Published 2019 Jul 19. doi:https://​doi.​org/​10.​3390/​cells8070742
19.
go back to reference Ringholm S, Biensø RS, Kiilerich K, Guadalup-Grau A, Aachmann-Andersen NJ, Saltin B, Plomgaard P, Lundby C, Wojtaszewski JFP, Calbet JA, Pilegaard H (2011) Bed rest reduces metabolic protein content and abolishes exercise-induced mRNA responses in human skeletal muscle. Am J Physiol Endocrinol Metab 301:E649–E658. https://doi.org/10.1152/ajpendo.00230.2011CrossRefPubMed Ringholm S, Biensø RS, Kiilerich K, Guadalup-Grau A, Aachmann-Andersen NJ, Saltin B, Plomgaard P, Lundby C, Wojtaszewski JFP, Calbet JA, Pilegaard H (2011) Bed rest reduces metabolic protein content and abolishes exercise-induced mRNA responses in human skeletal muscle. Am J Physiol Endocrinol Metab 301:E649–E658. https://​doi.​org/​10.​1152/​ajpendo.​00230.​2011CrossRefPubMed
20.
go back to reference Ling S, Zhong G, Sun W, Liang F, Wu F, Li H, Li Y, Zhao D, Song J, Jim X, Wu X, Song H, Li Q, Li Y, Chen S, Xiong J, Li Y (2017) Circulating micrornas correlated with bone loss induced by 45 days of bed rest. Front Physiol 8:69. Published 2017 Feb 14. doi:https://doi.org/10.3389/fphys.2017.00069 Ling S, Zhong G, Sun W, Liang F, Wu F, Li H, Li Y, Zhao D, Song J, Jim X, Wu X, Song H, Li Q, Li Y, Chen S, Xiong J, Li Y (2017) Circulating micrornas correlated with bone loss induced by 45 days of bed rest. Front Physiol 8:69. Published 2017 Feb 14. doi:https://​doi.​org/​10.​3389/​fphys.​2017.​00069
24.
go back to reference Vincent WJ, Weir JP (2012) Statistics in kinesiology. Human Kinetics, Champaign IL Vincent WJ, Weir JP (2012) Statistics in kinesiology. Human Kinetics, Champaign IL
25.
go back to reference Shuhart CR, Yeap SS, Anderson PA, Jankowski LG, Lewiecki EM, Morse LR, Rosen HN, Weber DR, Zemel BS, Shepherd JA (2019) Executive summary of the 2019 ISCD position development conference on monitoring treatment, DXA cross-calibration and least significant change, spinal cord injury, peri-prosthetic and orthopedic bone health, transgender medicine, and pediatrics. J Clin Densitom 22(4):453–471. https://doi.org/10.1016/j.jocd.2019.07.001CrossRefPubMed Shuhart CR, Yeap SS, Anderson PA, Jankowski LG, Lewiecki EM, Morse LR, Rosen HN, Weber DR, Zemel BS, Shepherd JA (2019) Executive summary of the 2019 ISCD position development conference on monitoring treatment, DXA cross-calibration and least significant change, spinal cord injury, peri-prosthetic and orthopedic bone health, transgender medicine, and pediatrics. J Clin Densitom 22(4):453–471. https://​doi.​org/​10.​1016/​j.​jocd.​2019.​07.​001CrossRefPubMed
26.
go back to reference Morgan JL, Heer M, Hargens AR, Macias BR, Hudson EK, Shackelford LC, Zwart SR, Smith SM (2014) Sex-specific responses of bone metabolism and renal stone risk during bed rest. Physiol Rep. 2:e12119. Published 2014 Aug 7. doi:https://doi.org/10.14814/phy2.12119 Morgan JL, Heer M, Hargens AR, Macias BR, Hudson EK, Shackelford LC, Zwart SR, Smith SM (2014) Sex-specific responses of bone metabolism and renal stone risk during bed rest. Physiol Rep. 2:e12119. Published 2014 Aug 7. doi:https://​doi.​org/​10.​14814/​phy2.​12119
33.
go back to reference Lang T, Van Loon JJWA, Bloomfield S, Vico L, Chopard A, Rittweger J, Kyparos A, Blottner D, Vuori I, Gerzer R, Cavanagh PR (2017) Towards human exploration of space: the THESEUS review series on muscle and bone research priorities. NPJ Microgravity 3:8 Published 2017 Feb 14. doi:https://doi.org/10.1038/s41526-017-0013-0 Lang T, Van Loon JJWA, Bloomfield S, Vico L, Chopard A, Rittweger J, Kyparos A, Blottner D, Vuori I, Gerzer R, Cavanagh PR (2017) Towards human exploration of space: the THESEUS review series on muscle and bone research priorities. NPJ Microgravity 3:8 Published 2017 Feb 14. doi:https://​doi.​org/​10.​1038/​s41526-017-0013-0
Metadata
Title
Circulating MiR-21 expression is upregulated after 30 days of head-down tilt bed rest
Authors
D.A. Bemben
B.S. Baker
S.R. Buchanan
C.J. Ade
Publication date
01-07-2021
Publisher
Springer London
Published in
Osteoporosis International / Issue 7/2021
Print ISSN: 0937-941X
Electronic ISSN: 1433-2965
DOI
https://doi.org/10.1007/s00198-020-05805-2

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