Bone-Regulating MicroRNAs and Resistance Exercise: A Mini-Review
Abstract
:1. Introduction
2. MiRNA Physiology
3. Regulatory Role of MiRNAs in Bone Metabolism
4. MiRNAs and Osteoporosis
5. MiRNAs and Mechanical Loading
5.1. Skeletal Muscle MiRNAs
5.2. Circulating MiRNAs
Study | RE Protocol | Target Population | Sample | Upregulation | MiRNA Responses Downregulation | No Change |
---|---|---|---|---|---|---|
Drummond et al. [29] | Leg extension 8 sets 10 reps 70% 1RM | Young men (n = 6) Older men (n = 6) | Muscle | Young only miR-1 | Young miR-133a miR-206 All in older men | |
Sawada et al. [32] | Bench press Leg Press 5 sets 10 reps 70% 1RM | Young men (n = 12) | Serum | miR-149 | miR-146a miR-221 | |
Rivas et al. [30] | Bilateral Knee Extension 3 sets 10 reps 80% 1RM | Young men (n = 8) Older men (n = 8) | Muscle | Young only miR-486-5p | Young only miR-23b-3p -24-3p, -26a-3p -27a-3p, -27b-3p -29c-3p, -30a-5p -30d-5p, -95-3p -126-3p, -133a -133b, -140-3p -181a-3p, -378a-5p | All in older men |
Margolis et al. [33] | Bilateral Knee Extension, Leg Press 3 sets 10 reps 80% 1RM | Young men (n = 9) Older men (n = 9) | Serum | Young miR-221-3p -222-3p -206 | Older miR-31-5p -124-3p, -211-5p -375 | |
D’Souza et al. [34] | Leg press 6 sets 8–10 reps 80% 1RM Knee extension 8 sets 8–10 reps 80% 1RM | Young men (n = 9) | Muscle Plasma | Muscle miR-23a-3p, -133a-3p, -146a-5p, -206a, -378b -486-5p Plasma miR-133a-3p -149-5p | ||
Cui et al. [35] | Bench press, Squat, Pull-down, Overhead Press, Dumbbell Curl Hypertrophy 3 sets 12 reps 70% 1RM Strength 4 sets 6 reps 90% 1RM Strength Endurance | Young men (n = 45) | Plasma | Hypertrophy miR-133b -181a, -206 Strength miR-133b Strength-Endurance miR-532 | Hypertrophy miR-21 -133a, -221 Strength miR-133a Strength-Endurance miR-208b | |
3 sets 16–20 reps 40% 1RM | ||||||
Telles et al. [31] | Leg press Knee extension 4 sets 8–12 RM High-intensity interval exercise (HIIE) Concurrent resistance and high-intensity interval exercise (CON) | Young men (n = 9) | Muscle | all 3 protocols miR-1-3p -133a-3p -133b-3p -181a-3p -486, RE > HIIE, CON miR-23a-3p,-206 | all 3 protocols miR-378a-5p | |
Buchanan [36] | Leg press Shoulder press Lat pulldown Knee extension Hip adduction 3 sets 10 reps 70–75% 1RM Whole-body vibration (WBV) 5–1 min sets 3.38 mm peak-to-peak displacement 2.7 g | Postmenopausal women (n = 10) | Serum | WBV only miR-21-5p | all for RE |
6. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
Abbreviations
BMD | bone mineral density |
BMP | Bone Morphogenetic Protein |
BMPR/BMPR2 BMP | receptor/type II |
c-miRNA | circulating microRNA |
CTX-I | C-telopeptide of Type I collagen cross-links |
CXCL11 C-X-C | Motif Chemokine Ligand 11 |
DXA | dual energy x-ray absorptiometry |
eIF4E3 Eukaryotic | translation initiation factor 4E family member 3 |
FASL | Fas Ligand |
FC | fold change |
KDM6B | Lysine Demethylase 6B |
MAPK | Mitogen-Activated Protein Kinase |
miRNA | microRNA |
c-miRNA | circulating miRNA |
MAFB | V-maf musculoaponeurotic fibrosarcoma oncogene homolog B |
MCSA | Muscle cross-sectional area |
MMP13 | Matrix Metalloproteinase 13 |
nt | nucleotides |
OSX | Osterix |
PDCD4 | Programmed Cell Death Protein 4 |
RE | resistance exercise |
1 RM 1 | Repetition Maximum |
RNA | Ribonucleic Acid |
RUNX2 | Runt-Related Transcription Factor 2 |
SMAD1 | Small Mothers Against Decapentaplegic 1 |
SMAD3 | Small Mothers Against Decapentaplegic 3 |
SMAD7 | Small Mothers Against Decapentaplegic 7 |
TGF-β | Transforming Growth Factor-Beta |
TRAP5b | Tartrate-resistant acid phosphatase 5b |
WBV | whole-body vibration |
Wnt Wingless-Type MMTV Integration Site Family |
References
- Van Wijnen, A.J.; van de Peppel, J.; van Leeuwen, J.P.; Lian, J.B.; Stein, G.S.; Westendorf, J.J.; Oursler, M.-J.; Im, H.-J.; Taipaleenmäki, H.; Hesse, E.; et al. MicroRNA functions in osteogenesis and dysfunctions in osteoporosis. Curr. Osteoporos. Rep. 2013, 11, 72–82. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Hackl, M.; Heilmeier, U.; Weilner, S.; Grillari, J. Circulating microRNAs as novel biomarkers for bone diseases—Complex signatures for multifactorial diseases? Mol. Cell Endocrinol. 2016, 432, 83–95. [Google Scholar] [CrossRef] [PubMed]
- Bellavia, D.; De Luca, A.; Carina, V.; Costa, V.; Raimondi, L.; Salamanna, F.; Alessandro, R.; Fini, M.; Giavaresi, G. Deregulated miRNAs in bone health: Epigenetic roles in osteoporosis. Bone 2019, 122, 52–75. [Google Scholar] [CrossRef]
- Landgraf, P.; Rusu, M.; Sheridan, R.; Sewer, A.; Iovino, N.; Aravin, A.; Pfeffer, S.; Rice, A.; Kamphorst, A.O.; Landthaler, M.; et al. A mammalian microRNA expression atlas based on small RNA library sequencing. Cell 2007, 129, 1401–1414. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Seeliger, C.; Karpinski, K.; Haug, A.T.; Vester, H.; Schmitt, A.; Bauer, J.S.; van Griensven, M. Five freely circulating miRNAs and bone tissue miRNAs are associated with osteoporotic fractures. J. Bone Miner. Res. 2014, 29, 1718–1728, Erratum in J. Bone. Miner. Res. 2015, 30, 195–196. [Google Scholar] [CrossRef]
- Panach, L.; Mifsut, D.; Tarín, J.J.; Cano, A.; García-Pérez, M.Á. Serum Circulating MicroRNAs as Biomarkers of Osteoporotic Fracture. Calcif. Tissue Int. 2015, 97, 495–505. [Google Scholar] [CrossRef]
- Kelch, S.; Balmayor, E.R.; Seeliger, C.; Vester, H.; Kirschke, J.S.; van Griensven, M. miRNAs in bone tissue correlate to bone mineral density and circulating miRNAs are gender independent in osteoporotic patients. Sci. Rep. 2017, 7, 15861. [Google Scholar] [CrossRef] [PubMed]
- Zhao, W.; Shen, G.; Ren, R.; Liang, D.; Yu, X.; Zhang, Z.; Huang, J.; Qiu, T.; Tang, J.; Shang, Q.; et al. Therapeutic potential of microRNAs in osteoporosis function by regulating the biology of cells related to bone homeostasis. J. Cell Physiol. 2018, 233, 9191–9208. [Google Scholar] [CrossRef]
- Sapp, R.M.; Shill, D.D.; Roth, S.M.; Hagberg, J.M. Circulating microRNAs in acute and chronic exercise: More than mere biomarkers. J. Appl. Physiol. 2017, 122, 702–717. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Fernández-Sanjurjo, M.; de Gonzalo-Calvo, D.; Fernández-García, B.; Sergio, D.-R.; Ángel, M.-C.; Hugo, O.; Alberto, D.; Eduardo, I.-G. Circulating microRNA as Emerging Biomarkers of Exercise. Exerc. Sport Sci. Rev. 2018, 46, 160–171. [Google Scholar] [CrossRef]
- Shojaa, M.; von Stengel, S.; Kohl, M.; Schoene, D.; Kemmler, W. Effects of dynamic resistance exercise on bone mineral density in postmenopausal women: A systematic review and meta-analysis with special emphasis on exercise parameters. Osteoporos. Int. 2020, 31, 1427–1444. [Google Scholar] [CrossRef] [PubMed]
- Pasqualini, L.; Ministrini, S.; Lombardini, R.; Bagaglia, F.; Paltriccia, R.; Pippi, R.; Collebrusco, L.; Reginato, E.; Sbroma Tomaro, E.; Marini, E.; et al. Effects of a 3-month weight-bearing and resistance exercise training on circulating osteogenic cells and bone formation markers in postmenopausal women with low bone mass. Osteoporos. Int. 2019, 30, 797–806. [Google Scholar] [CrossRef] [PubMed]
- Bartel, D.P. Metazoan microRNAs. Cell 2018, 173, 20–51. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Friedman, R.C.; Farh, K.K.; Burge, C.B.; Bartel, D.P. Most mammalian mRNAs are conserved targets of microRNAs. Genome Res. 2009, 19, 92–105. [Google Scholar] [CrossRef] [Green Version]
- Plotkin, L.I.; Wallace, J.M. MicroRNAs and osteocytes. Bone 2021, 150, 115994. [Google Scholar] [CrossRef] [PubMed]
- Moore, B.T.; Xiao, P. MiRNAs in bone diseases. Microrna 2013, 2, 20–31. [Google Scholar] [CrossRef]
- Hu, C.H.; Sui, B.D.; Du, F.Y.; Shuai, Y.; Zheng, C.X.; Zhao, P.; Yu, X.R.; Jin, Y. miR-21 deficiency inhibits osteoclast function and prevents bone loss in mice. Sci. Rep. 2017, 7, 43191. [Google Scholar] [CrossRef] [Green Version]
- Cheng, V.K.; Au, P.C.; Tan, K.C.; Cheung, C.L. MicroRNA and human bone health. JBMR Plus. 2018, 3, 2–13. [Google Scholar] [CrossRef]
- Sugatani, T.; Vacher, J.; Hruska, K.A. A microRNA expression signature of osteoclastogenesis. Blood 2011, 117, 3648–3657. [Google Scholar] [CrossRef]
- Gennari, L.; Bianciardi, S.; Merlotti, D. MicroRNAs in bone diseases. Osteoporos. Int. 2017, 28, 1191–1213. [Google Scholar] [CrossRef]
- Sugatani, T.; Hruska, K.A. Down-regulation of miR-21 biogenesis by estrogen action contributes to osteoclastic apoptosis. J. Cell Biochem. 2013, 114, 1217–1222. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Hassan, M.Q.; Gordon, J.A.; Beloti, M.M.; Croce, C.M.; van Wijnen, A.J.; Stein, J.L.; Stein, G.S.; Liana, J.B. A network connecting Runx2, SATB2, and the miR-23a∼27a∼24-2 cluster regulates the osteoblast differentiation program. Proc. Natl. Acad. Sci. USA 2010, 107, 19879–19884. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Chen, Z.; Bemben, M.G.; Bemben, D.A. Bone and muscle specific circulating microRNAs in postmenopausal women based on osteoporosis and sarcopenia status. Bone 2019, 120, 271–278. [Google Scholar] [CrossRef]
- Wang, J.; Cui, Q. Specific roles of microRNAs in their interactions with environmental factors. J. Nucleic Acids 2012, 2012, 978384. [Google Scholar] [CrossRef]
- Weilner, S.; Skalicky, S.; Salzer, B.; Keider, V.; Wagner, M.; Hildner, F.; Gabriel, C.; Dovjak, P.; Pietschmann, P.; Grillari-Voglauer, R.; et al. Differentially circulating miRNAs after recent osteoporotic fractures can influence osteogenic differentiation. Bone 2015, 79, 43–51. [Google Scholar] [CrossRef] [Green Version]
- Yuan, Y.; Zhang, L.; Tong, X.; Zhang, M.; Zhao, Y.; Guo, J.; Lei, L.; Chen, X.; Tickner, J.; Xu, J.; et al. Mechanical stress regulates bone metabolism through microRNAs. J. Cell Physiol. 2017, 232, 1239–1245. [Google Scholar] [CrossRef]
- Wei, F.; Liu, D.; Feng, C.; Zhang, F.; Yang, S.; Hu, Y.; Ding, G.; Wang, S. MicroRNA-21 mediates stretch-induced osteogenic differentiation in human periodontal ligament stem cells. Stem. Cells Dev. 2015, 24, 312–319. [Google Scholar] [CrossRef] [Green Version]
- Mai, Z.H.; Peng, Z.L.; Zhang, J.L.; Chen, L.; Liang, H.Y.; Cai, B.; Ai, H. miRNA expression profile during fluid shear stress-induced osteogenic differentiation in MC3T3-E1 cells. Chin. Med. J. (Eng) 2013, 126, 1544–1550. [Google Scholar]
- Drummond, M.J.; McCarthy, J.J.; Fry, C.S.; Esser, K.A.; Rasmussen, B.B. Aging differentially affects human skeletal muscle microRNA expression at rest and after an anabolic stimulus of resistance exercise and essential amino acids. Am. J. Physiol. Endocrinol. Metab. 2008, 295, E1333–E1340. [Google Scholar] [CrossRef] [Green Version]
- Rivas, D.A.; Lessard, S.J.; Rice, N.P.; Lustgarten, M.S.; So, K.; Goodyear, L.J.; Parnell, L.D.; Fielding, R.A. Diminished skeletal muscle microRNA expression with aging is associated with attenuated muscle plasticity and inhibition of IGF-1 signaling. FASEB J. 2014, 28, 4133–4147. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Telles, G.D.; Libardi, C.A.; Conceição, M.S.; Vechin, F.C.; Lixandrão, M.E.; DE Andrade, A.L.L.; Guedes, D.N.; Ugrinowitsch, C.; Camera, D.M. Time Course of skeletal muscle miRNA expression after resistance, high-intensity interval, and concurrent exercise. Med. Sci. Sports Exerc. 2021, 53, 1708–1718. [Google Scholar] [CrossRef] [PubMed]
- Sawada, S.; Kon, M.; Wada, S.; Ushida, T.; Suzuki, K.; Akimoto, T. Profiling of circulating microRNAs after a bout of acute resistance exercise in humans. PLoS ONE 2013, 8, e70823. [Google Scholar] [CrossRef] [PubMed]
- Margolis, L.M.; Lessard, S.J.; Ezzyat, Y.; Fielding, R.A.; Rivas, D.A. Circulating microRNA are predictive of aging and acute adaptive response to resistance exercise in men. J. Gerontol. A Biol. Sci. Med. Sci. 2017, 72, 1319–1326. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- D’Souza, R.F.; Markworth, J.F.; Aasen, K.M.M.; Zeng, N.; Cameron-Smith, D.; Mitchell, C.J. Acute resistance exercise modulates microRNA expression profiles: Combined tissue and circulatory targeted analyses. PLoS ONE 2017, 12, e0181594. [Google Scholar] [CrossRef]
- Cui, S.; Sun, B.; Yin, X.; Guo, X.; Chao, D.; Zhang, C.; Zhang, C.Y.; Chen, X.; Ma, J. Time-course responses of circulating microRNAs to three resistance training protocols in healthy young men. Sci. Rep. 2017, 7, 2203. [Google Scholar] [CrossRef] [Green Version]
- Buchanan, S.R. Alterations of c-miRNA Expression from Whole-body Vibration and Resistance Exercise in Postmenopausal Women. Doctoral Dissertation, University of Oklahoma, Norman, Oklahoma, 2019. SHAREOK repository. Available online: https://hdl.handle.net/11244/321121 (accessed on 22 February 2021).
MiRNA | Target Gene | Pathway/Enzyme | Biological Effect |
---|---|---|---|
miR-21-5p | SMAD7 PDCD4 | BMP, TGF-β c-Fos | Promote OB differentiation Promote OC differentiation |
miR-23a-3p | RUNX2 SMAD3 | TGF-β | Suppress OB differentiation Suppress OB differentiation |
miR-100-5p | BMPR2 SMAD1 | BMP BMP | Suppress OB differentiation Suppress OB differentiation |
miR-125b-5p | BMPR OSX | BMP RUNX2 | Suppress OB differentiation Suppress OB differentiation |
miR-126-3p | MMP13 | Matrix Degeneration | Suppress OC differentiation |
miR-133a-3p | RUNX2 CXCL11 | Rank | Suppress OB differentiation Promote OC differentiation |
miR-148a-3p | KDM6B MAFB | TGF-β Rank | Suppress OB differentiation Promote OC differentiation |
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Bemben, D.A.; Chen, Z.; Buchanan, S.R. Bone-Regulating MicroRNAs and Resistance Exercise: A Mini-Review. Osteology 2022, 2, 11-20. https://doi.org/10.3390/osteology2010002
Bemben DA, Chen Z, Buchanan SR. Bone-Regulating MicroRNAs and Resistance Exercise: A Mini-Review. Osteology. 2022; 2(1):11-20. https://doi.org/10.3390/osteology2010002
Chicago/Turabian StyleBemben, Debra A., Zhaojing Chen, and Samuel R. Buchanan. 2022. "Bone-Regulating MicroRNAs and Resistance Exercise: A Mini-Review" Osteology 2, no. 1: 11-20. https://doi.org/10.3390/osteology2010002