Wnt and β-Catenin Signaling and Skeletal Muscle Myogenesis in Response to Muscle Damage and Resistance Exercise and Training

Dan Newmire, Darryn S. Willoughby

Abstract


The factors that regulate skeletal muscle hypertrophy in human adults in response to resistance training (RT) has largely focused on endogenous endocrine responses. However, the endocrine response to RT as having an obligatory role in muscle hypertrophy has come under scrutiny, as other mechanisms and pathways seem to also be involved in up-regulating muscle protein synthesis (MPS). Skeletal muscle myogenesis is a multifactorial process of tissue growth and repair in response to resistance training is regulated by many factors.  As a result, satellite cell-fused myogenesis is a possible factor in skeletal muscle regeneration and hypertrophy in response to RT.  The Wnt family ligands interact with various receptors and activate different downstream signaling pathways and have been classified as either canonical (β-catenin dependent) or non-canonical (β-catenin independent).  Wnt is secreted from numerous tissues in a paracrine fashion. The Wnt/β-catenin signaling pathway is a highly-regulated and intricate pathway that is essential to skeletal muscle myogenesis.  The canonical Wnt/β-catenin pathway may influence satellite cells to myogenic commitment, differentiation, and fusion into muscle fibers in response to injury or trauma, self-renewal, and normal basal turnover.  The current literature has shown that, in response mechanical overload from acute resistance exercise and chronic resistance training, that the Wnt/β-catenin signaling pathway is stimulated which may actuate the process of muscle repair and hypertrophy in response to exercise-induced muscle damage. The purpose of this review is to elaborate on the Wnt/β-catenin signaling  pathway, the current literature investigating the relationship of the Wnt/β-catenin pathway and its effects on myogenesis is response to muscle damage and resistance exercise and training.     

Keywords: skeletal muscle, hypertrophy, myogenesis, cell signaling, protein synthesis, resistance training


Full Text:

PDF

References


References

Abu-Elmagd, M., Robson, L., Sweetman, D., Hadley, J., Francis-West, P., & Munsterberg, A. (2010). Wnt/Lef1 signaling acts via Pitx2 to regulate somite myogenesis. Developmental Biology, 337(2), 211-219. doi:10.1016/j.ydbio.2009.10.023

Adegoke, O. A., Abdullahi, A., & Tavajohi-Fini, P. (2012). mTORC1 and the regulation of skeletal muscle anabolism and mass. Applied Physiology, Nutrition, and Metabolism, 37(3), 395-406. doi:10.1139/h2012-009

Agustí, A. G., Sauleda, J., Miralles, C., Gomez, C., Togores, B., Sala, E., . . . Busquets, X. (2002). Skeletal muscle apoptosis and weight loss in chronic obstructive pulmonary disease. American Journal of Respiratory and Critical Care Medicine, 166(4), 485-489.

Amin, H., Vachris, J., Hamilton, A., Steuerwald, N., Howden, R., & Arthur, S. T. (2014). GSK3beta inhibition and LEF1 upregulation in skeletal muscle following a bout of downhill running. Journal of Physiological Sciences, 64(1), 1-11. doi:10.1007/s12576-013-0284-5

Angers, S., & Moon, R. T. (2009). Proximal events in Wnt signal transduction. Nature reviews Molecular cell biology, 10(7), 468-477.

Armstrong, D. D., & Esser, K. A. (2005). Wnt/beta-catenin signaling activates growth-control genes during overload-induced skeletal muscle hypertrophy. American Journal of Physiology: Cell Physiology, 289(4), C853-859. doi:10.1152/ajpcell.00093.2005

Baarsma, H. A., Konigshoff, M., & Gosens, R. (2013). The WNT signaling pathway from ligand secretion to gene transcription: molecular mechanisms and pharmacological targets. Pharmacology & Therapeutics, 138(1), 66-83. doi:10.1016/j.pharmthera.2013.01.002

Bellamy, L. M., Joanisse, S., Grubb, A., Mitchell, C. J., McKay, B. R., Phillips, S. M., . . . Parise, G. (2014). The acute satellite cell response and skeletal muscle hypertrophy following resistance training. PloS One, 9(10), e109739. doi:10.1371/journal.pone.0109739

Bentzinger, C. F., Wang, Y. X., & Rudnicki, M. A. (2012). Building Muscle: Molecular Regulation of Myogenesis. Cold Spring Harbor Perspectives in Biology, 4(2).

Bernardi, H., Gay, S., Fedon, Y., Vernus, B., Bonnieu, A., & Bacou, F. (2011). Wnt4 activates the canonical beta-catenin pathway and regulates negatively myostatin: functional implication in myogenesis. American Journal of Physiology: Cell Physiology, 300(5), C1122-1138. doi:10.1152/ajpcell.00214.2010

Brack, A. S., Murphy-Seiler, F., Hanifi, J., Deka, J., Eyckerman, S., Keller, C., . . . Rando, T. A. (2009). BCL9 is an essential component of canonical Wnt signaling that mediates the differentiation of myogenic progenitors during muscle regeneration. Developmental Biology, 335(1), 93-105. doi:10.1016/j.ydbio.2009.08.014

Bryson-Richardson, R. J., & Currie, P. D. (2008). The genetics of vertebrate myogenesis. Nature Reviews: Genetics, 9(8), 632-646. doi:10.1038/nrg2369

Charge, S. B., & Rudnicki, M. A. (2004). Cellular and molecular regulation of muscle regeneration. Physiological Reviews, 84(1), 209-238. doi:10.1152/physrev.00019.2003

Ciciliot, S., & Schiaffino, S. (2010). Regeneration of mammalian skeletal muscle. Basic mechanisms and clinical implications. Current Pharmaceutical Design, 16(8), 906-914. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/20041823

Clevers, H., & Nusse, R. (2012). Wnt/beta-catenin signaling and disease. Cell, 149(6), 1192-1205. doi:10.1016/j.cell.2012.05.012

Collins, C. A., Olsen, I., Zammit, P. S., Heslop, L., Petrie, A., Partridge, T. A., & Morgan, J. E. (2005). Stem cell function, self-renewal, and behavioral heterogeneity of cells from the adult muscle satellite cell niche. Cell, 122(2), 289-301. doi:10.1016/j.cell.2005.05.010

De Calisto, J., Araya, C., Marchant, L., Riaz, C. F., & Mayor, R. (2005). Essential role of non-canonical Wnt signalling in neural crest migration. Development, 132(11), 2587-2597. doi:10.1242/dev.01857

Drummond, M. J., Dreyer, H. C., Fry, C. S., Glynn, E. L., & Rasmussen, B. B. (2009). Nutritional and contractile regulation of human skeletal muscle protein synthesis and mTORC1 signaling. J Appl Physiol (1985), 106(4), 1374-1384. doi:10.1152/japplphysiol.91397.2008

Eaton, S. (2008). Retromer retrieves wntless. Developmental Cell, 14(1), 4-6. doi:10.1016/j.devcel.2007.12.014

Fu, X., Wang, H., & Hu, P. (2015). Stem cell activation in skeletal muscle regeneration. Cellular and Molecular Life Sciences, 72(9), 1663-1677.

Gao, B. (2012). Wnt regulation of planar cell polarity (PCP). Current Topics in Developmental Biology, 101, 263-295. doi:10.1016/B978-0-12-394592-1.00008-9

Gao, C., Xiao, G., & Hu, J. (2014). Regulation of Wnt/β-catenin signaling by posttranslational modifications. Cell Biosci, 4(1), 13.

Gilson, H., Schakman, O., Kalista, S., Lause, P., Tsuchida, K., & Thissen, J. P. (2009). Follistatin induces muscle hypertrophy through satellite cell proliferation and inhibition of both myostatin and activin. American Journal of Physiology: Endocrinology and Metabolism, 297(1), E157-164. doi:10.1152/ajpendo.00193.2009

Gomez-Orte, E., Saenz-Narciso, B., Moreno, S., & Cabello, J. (2013). Multiple functions of the noncanonical Wnt pathway. Trends in Genetics, 29(9), 545-553. doi:10.1016/j.tig.2013.06.003

Grobet, L., Martin, L. J., Poncelet, D., Pirottin, D., Brouwers, B., Riquet, J., . . . Georges, M. (1997). A deletion in the bovine myostatin gene causes the double-muscled phenotype in cattle. Nature Genetics, 17(1), 71-74. doi:10.1038/ng0997-71

Han, X. H., Jin, Y. R., Seto, M., & Yoon, J. K. (2011). A WNT/beta-catenin signaling activator, R-spondin, plays positive regulatory roles during skeletal myogenesis. Journal of Biological Chemistry, 286(12), 10649-10659. doi:10.1074/jbc.M110.169391

Hasani-Ranjbar, S., Soleymani Far, E., Heshmat, R., Rajabi, H., & Kosari, H. (2012). Time course responses of serum GH, insulin, IGF-1, IGFBP1, and IGFBP3 concentrations after heavy resistance exercise in trained and untrained men. Endocrine, 41(1), 144-151. doi:10.1007/s12020-011-9537-3

Hausmann, G., & Basler, K. (2006). Wnt lipid modifications: not as saturated as we thought. Developmental Cell, 11(6), 751-752. doi:10.1016/j.devcel.2006.11.007

Hornberger, T. A., Sukhija, K. B., & Chien, S. (2006). Regulation of mTOR by mechanically induced signaling events in skeletal muscle. Cell Cycle, 5(13), 1391-1396. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/16855395

Janssen, I., Heymsfield, S. B., Wang, Z., & Ross, R. (2000). Skeletal muscle mass and distribution in 468 men and women aged 18–88 yr. Journal of Applied Physiology, 89(1), 81-88.

Jones, A. E., Price, F. D., Le Grand, F., Soleimani, V. D., Dick, S. A., Megeney, L. A., & Rudnicki, M. A. (2015). Wnt/β-catenin controls follistatin signalling to regulate satellite cell myogenic potential. Skelet Muscle, 5(1), 14.

Joulia-Ekaza, D., & Cabello, G. (2007). The myostatin gene: physiology and pharmacological relevance. Current Opinion in Pharmacology, 7(3), 310-315. doi:10.1016/j.coph.2006.11.011

Karalaki, M., Fili, S., Philippou, A., & Koutsilieris, M. (2009). Muscle regeneration: cellular and molecular events. In Vivo, 23(5), 779-796. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/19779115

Koles, K., Nunnari, J., Korkut, C., Barria, R., Brewer, C., Li, Y., . . . Budnik, V. (2012). Mechanism of evenness interrupted (Evi)-exosome release at synaptic boutons. Journal of Biological Chemistry, 287(20), 16820-16834. doi:10.1074/jbc.M112.342667

Korkut, C., Ataman, B., Ramachandran, P., Ashley, J., Barria, R., Gherbesi, N., & Budnik, V. (2009). Trans-synaptic transmission of vesicular Wnt signals through Evi/Wntless. Cell, 139(2), 393-404. doi:10.1016/j.cell.2009.07.051

Kraemer, R. R., & Castracane, V. D. (2015). Endocrine alterations from concentric vs. eccentric muscle actions: a brief review. Metabolism, 64(2), 190-201. doi:10.1016/j.metabol.2014.10.024

Kraemer, W. J., Duncan, N. D., & Volek, J. S. (1998). Resistance training and elite athletes: adaptations and program considerations. Journal of Orthopaedic and Sports Physical Therapy, 28(2), 110-119. doi:10.2519/jospt.1998.28.2.110

Kraemer, W. J., Hakkinen, K., Newton, R. U., Nindl, B. C., Volek, J. S., McCormick, M., . . . Evans, W. J. (1999). Effects of heavy-resistance training on hormonal response patterns in younger vs. older men. J Appl Physiol (1985), 87(3), 982-992. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/10484567

Laplante, M., & Sabatini, D. M. (2009). mTOR signaling at a glance. Journal of Cell Science, 122(20), 3589-3594.

Le Grand, F., & Rudnicki, M. A. (2007). Skeletal muscle satellite cells and adult myogenesis. Current Opinion in Cell Biology, 19(6), 628-633.

Leal, M. L., Lamas, L., Aoki, M. S., Ugrinowitsch, C., Ramos, M. S., Tricoli, V., & Moriscot, A. S. (2011). Effect of different resistance-training regimens on the WNT-signaling pathway. European Journal of Applied Physiology, 111(10), 2535-2545. doi:10.1007/s00421-011-1874-7

Li, V. S., Ng, S. S., Boersema, P. J., Low, T. Y., Karthaus, W. R., Gerlach, J. P., . . . Clevers, H. (2012). Wnt signaling through inhibition of beta-catenin degradation in an intact Axin1 complex. Cell, 149(6), 1245-1256. doi:10.1016/j.cell.2012.05.002

Logan, C. Y., & Nusse, R. (2004). The Wnt signaling pathway in development and disease. Annual Review of Cell and Developmental Biology, 20, 781-810. doi:10.1146/annurev.cellbio.20.010403.113126

Madarame, H., Sasaki, K., & Ishii, N. (2010). Endocrine responses to upper- and lower-limb resistance exercises with blood flow restriction. Acta Physiologica Hungarica, 97(2), 192-200. doi:10.1556/APhysiol.97.2010.2.5

Mann, R. K., & Beachy, P. A. (2004). Novel lipid modifications of secreted protein signals. Annual Review of Biochemistry, 73, 891-923. doi:10.1146/annurev.biochem.73.011303.073933

Mitchell, C. J., Churchward-Venne, T. A., Parise, G., Bellamy, L., Baker, S. K., Smith, K., . . . Phillips, S. M. (2014). Acute post-exercise myofibrillar protein synthesis is not correlated with resistance training-induced muscle hypertrophy in young men. PloS One, 9(2), e89431.

Mulholland, D. J., Cheng, H., Reid, K., Rennie, P. S., & Nelson, C. C. (2002). The androgen receptor can promote beta-catenin nuclear translocation independently of adenomatous polyposis coli. Journal of Biological Chemistry, 277(20), 17933-17943. doi:10.1074/jbc.M200135200

Niehrs, C., & Acebron, S. P. (2010). Wnt signaling: multivesicular bodies hold GSK3 captive. Cell, 143(7), 1044-1046. doi:10.1016/j.cell.2010.12.003

Nishita, M., Endo, M., & Minami, Y. (2013). [Regulation of cellular responses by non-canonical Wnt signaling]. Clinical Calcium, 23(6), 809-815. doi:CliCa1306809815

Nusse, R., & Varmus, H. (2012). Three decades of Wnts: a personal perspective on how a scientific field developed. EMBO Journal, 31(12), 2670-2684. doi:10.1038/emboj.2012.146

Otto, A., Schmidt, C., Luke, G., Allen, S., Valasek, P., Muntoni, F., . . . Patel, K. (2008). Canonical Wnt signalling induces satellite-cell proliferation during adult skeletal muscle regeneration. Journal of Cell Science, 121(Pt 17), 2939-2950. doi:10.1242/jcs.026534

Otto, A., Schmidt, C., & Patel, K. (2006). Pax3 and Pax7 expression and regulation in the avian embryo. Anatomy and Embryology, 211(4), 293-310. doi:10.1007/s00429-006-0083-3

Ozhan, G., & Weidinger, G. (2015). Wnt/β-catenin signaling in heart regeneration. Cell Regen (Lond), 4(1).

Polesskaya, A., Seale, P., & Rudnicki, M. A. (2003). Wnt signaling induces the myogenic specification of resident CD45+ adult stem cells during muscle regeneration. Cell, 113(7), 841-852. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/12837243

Relaix, F., Rocancourt, D., Mansouri, A., & Buckingham, M. (2005). A Pax3/Pax7-dependent population of skeletal muscle progenitor cells. Nature, 435(7044), 948-953.

Segalen, M., & Bellaiche, Y. (2009). Cell division orientation and planar cell polarity pathways. Seminars in Cell & Developmental Biology, 20(8), 972-977. doi:10.1016/j.semcdb.2009.03.018

Semenov, M. V., Habas, R., Macdonald, B. T., & He, X. (2007). SnapShot: Noncanonical Wnt Signaling Pathways. Cell, 131(7), 1378. doi:10.1016/j.cell.2007.12.011

Serrano, A. L., Baeza-Raja, B., Perdiguero, E., Jardi, M., & Munoz-Canoves, P. (2008). Interleukin-6 is an essential regulator of satellite cell-mediated skeletal muscle hypertrophy. Cell Metab, 7(1), 33-44. doi:10.1016/j.cmet.2007.11.011

Spillane, M., Schwarz, N., & Willoughby, D. S. (2015). Upper-body resistance exercise augments vastus lateralis androgen receptor-DNA binding and canonical Wnt/beta-catenin signaling compared to lower-body resistance exercise in resistance-trained men without an acute increase in serum testosterone. Steroids, 98, 63-71. doi:10.1016/j.steroids.2015.02.019

Steelman, C. A., Recknor, J. C., Nettleton, D., & Reecy, J. M. (2006). Transcriptional profiling of myostatin-knockout mice implicates Wnt signaling in postnatal skeletal muscle growth and hypertrophy. FASEB Journal, 20(3), 580-582. doi:10.1096/fj.05-5125fje

Takada, R., Satomi, Y., Kurata, T., Ueno, N., Norioka, S., Kondoh, H., . . . Takada, S. (2006). Monounsaturated fatty acid modification of Wnt protein: its role in Wnt secretion. Developmental Cell, 11(6), 791-801. doi:10.1016/j.devcel.2006.10.003

Tanneberger, K., Pfister, A. S., Kriz, V., Bryja, V., Schambony, A., & Behrens, J. (2011). Structural and functional characterization of the Wnt inhibitor APC membrane recruitment 1 (Amer1). Journal of Biological Chemistry, 286(22), 19204-19214. doi:10.1074/jbc.M111.224881

Terada, K., Misao, S., Katase, N., Nishimatsu, S., & Nohno, T. (2013). Interaction of Wnt Signaling with BMP/Smad Signaling during the Transition from Cell Proliferation to Myogenic Differentiation in Mouse Myoblast-Derived Cells. International Journal of Cell Biology, 2013, 616294. doi:10.1155/2013/616294

Tesch, P. A. (1988). Skeletal muscle adaptations consequent to long-term heavy resistance exercise. Medicine & Science in Sports & Exercise, 20(5 Suppl), S132-134.

Thomas, D. R. (2007). Loss of skeletal muscle mass in aging: examining the relationship of starvation, sarcopenia and cachexia. Clinical Nutrition, 26(4), 389-399.

Uchida, M. C., Crewther, B. T., Ugrinowitsch, C., Bacurau, R. F., Moriscot, A. S., & Aoki, M. S. (2009). Hormonal responses to different resistance exercise schemes of similar total volume. Journal of Strength and Conditioning Research, 23(7), 2003-2008. doi:10.1519/JSC.0b013e3181b73bf7

van Amerongen, R., & Nusse, R. (2009). Towards an integrated view of Wnt signaling in development. Development, 136(19), 3205-3214.

von Maltzahn, J., Bentzinger, C. F., & Rudnicki, M. A. (2012). Wnt7a-Fzd7 signalling directly activates the Akt/mTOR anabolic growth pathway in skeletal muscle. Nature Cell Biology, 14(2), 186-191. doi:10.1038/ncb2404

von Maltzahn, J., Chang, N. C., Bentzinger, C. F., & Rudnicki, M. A. (2012). Wnt signaling in myogenesis. Trends in Cell Biology, 22(11), 602-609.

Walker, D. K., Dickinson, J. M., Timmerman, K. L., Drummond, M. J., Reidy, P. T., Fry, C. S., . . . Rasmussen, B. B. (2011). Exercise, amino acids, and aging in the control of human muscle protein synthesis. Medicine & Science in Sports & Exercise, 43(12), 2249-2258. doi:10.1249/MSS.0b013e318223b037

Wang, Q., & McPherron, A. C. (2012). Myostatin inhibition induces muscle fibre hypertrophy prior to satellite cell activation. Journal of Physiology, 590(Pt 9), 2151-2165. doi:10.1113/jphysiol.2011.226001

West, D. W., Burd, N. A., Staples, A. W., & Phillips, S. M. (2010). Human exercise-mediated skeletal muscle hypertrophy is an intrinsic process. International Journal of Biochemistry and Cell Biology, 42(9), 1371-1375. doi:10.1016/j.biocel.2010.05.012

West, D. W., & Phillips, S. M. (2010). Anabolic processes in human skeletal muscle: restoring the identities of growth hormone and testosterone. Phys Sportsmed, 38(3), 97-104. doi:10.3810/psm.2010.10.1814

Willert, K., & Nusse, R. (2012). Wnt proteins. Cold Spring Harbor Perspectives in Biology, 4(9), a007864. doi:10.1101/cshperspect.a007864

Williams, M. S. (2004). Myostatin mutation associated with gross muscle hypertrophy in a child. New England Journal of Medicine, 351(10), 1030-1031; author reply 1030-1031. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/15352277

Yin, H., Price, F., & Rudnicki, M. A. (2013). Satellite Cells and the Muscle Stem Cell Niche. Physiological Reviews, 93(1), 23-67.

Yokoyama, N., Markova, N. G., Wang, H. Y., & Malbon, C. C. (2012). Assembly of Dishevelled 3-based supermolecular complexes via phosphorylation and Axin. J Mol Signal, 7(1), 8. doi:10.1186/1750-2187-7-8

Yu, J., Chia, J., Canning, C. A., Jones, C. M., Bard, F. A., & Virshup, D. M. (2014). WLS retrograde transport to the endoplasmic reticulum during Wnt secretion. Developmental Cell, 29(3), 277-291. doi:10.1016/j.devcel.2014.03.016

Zhai, L., Chaturvedi, D., & Cumberledge, S. (2004). Drosophila wnt-1 undergoes a hydrophobic modification and is targeted to lipid rafts, a process that requires porcupine. Journal of Biological Chemistry, 279(32), 33220-33227. doi:10.1074/jbc.M403407200


Refbacks

  • There are currently no refbacks.


Bookmark and Share


Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.

2013-2023 (CC-BY) Australian International Academic Centre PTY.LTD.

International Journal of Kinesiology and Sports Science

You may require to add the 'aiac.org.au' domain to your e-mail 'safe list’ If you do not receive e-mail in your 'inbox'. Otherwise, you may check your 'Spam mail' or 'junk mail' folders.