Wnt Signaling–Related Osteokines at Rest and Following Plyometric Exercise in Prepubertal and Early Pubertal Boys and Girls

in Pediatric Exercise Science
Restricted access

Purchase article

USD  $24.95

Student 1 year subscription

USD  $68.00

1 year subscription

USD  $90.00

Student 2 year subscription

USD  $129.00

2 year subscription

USD  $168.00

Purpose: This study examined osteokines related to Wnt signaling at rest and in response to plyometric exercise in 12 boys [10.2 (0.4) y] and 12 girls [10.5 (0.4) y]. Methods: One resting (preexercise) and 3 postexercise (5 min, 1 h, and 24 h) blood samples were analyzed for sclerostin, dickkopf-related protein 1 (DKK-1), osteoprotegerin (OPG), and receptor activator of nuclear factor kappa-β ligand (RANKL). Results: Girls had higher resting sclerostin than boys [187.1 (40.1) vs 150.4 (36.4) pg·mL−1, respectively; P = .02]. However, boys had higher DKK-1 [427.7 (142.3) vs 292.8 (48.0) pg·mL−1, respectively; P = .02] and RANKL [3.9 (3.8) vs 1.0 (0.4) pg·mL−1, respectively; P < .01] than girls. In girls, sclerostin significantly decreased 5-minute and 1-hour postexercise (χ2 = 12.7, P = .01), and RANKL significantly decreased 5-minute postexercise (χ2 = 19.1, P < .01) and continued to decrease up to 24-hour postexercise, with large effect sizes. In boys, DKK-1 significantly decreased 1-hour postexercise and remained lower than preexercise 24-hour postexercise (χ2 = 13.0, P = .01). OPG increased in both boys (χ2 = 13.7, P < .01) and girls (χ2 = 11.4, P = .01), with boys having significantly higher OPG at 5-minute and 1-hour postexercise, whereas in girls, this increase was only seen 24-hour postexercise. Conclusion: Plyometric exercise induces an overall anabolic osteokine response favoring osteoblastogenesis over osteoclastogenesis in both boys and girls although the timeline and mechanism(s) may be different.

Klentrou, Angrish, Awadia, Kurgan, Kouvelioti, and Falk are with the Dept. of Kinesiology, Faculty of Applied Health Sciences, Brock University, St Catharines, Ontario, Canada.

Address author correspondence to Panagiota Klentrou at nklentrou@brocku.ca.
  • 1.

    Amrein K, Amrein S, Drexler C, et al. Sclerostin and its association with physical activity, age, gender, body composition and bone mineral content in healthy adults. J Clin Endocrinol Metab. 2012;97:148–54. doi:10.1210/jc.2011-2152

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 2.

    Beck BR. Exercise for bone in childhood—hitting the sweet spot. Pediatr Exerc Sci. 2017;29:1–23. PubMed doi:10.1123/pes.2017-0023

  • 3.

    Boyce BF, Xing L. Functions of RANKL/RANK/OPG in bone modeling and remodeling. Arch Biochem Biophys. 2008;473(2):139–46. PubMed doi:10.1016/j.abb.2008.03.018

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 4.

    Boyce BF, Xing L, Chen D. Osteoprotegerin, the bone protector, is a surprising target for β-catenin signaling. Cell Metab. 2005;2(6):344–5. PubMed doi:10.1016/j.cmet.2005.11.011

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 5.

    Burrows M. Exercise and bone mineral accrual in children and adolescents. J Sports Sci Med. 2007;6(3):305–12. PubMed

  • 6.

    Buzi F, Maccarinelli G, Guaragni B, et al. Serum osteoprotegerin and receptor activator of nuclear factors kB (RANKL) concentrations in normal children and in children with pubertal precocity, Turner’s syndrome and rheumatoid arthritis. Clin Endocrinol. 2004;60(1):87–91. PubMed doi:10.1111/j.1365-2265.2004.01951.x

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 7.

    Cohen JW. Statistical Power Analysis for the Behavioral Sciences. 2nd ed. Hillsdale, NJ: Lawrance Erlbaum Associates Inc; 1988.

  • 8.

    Dekker J, Nelson K, Kurgan N, Falk B, Josse A, Klentrou P. Wnt signaling-related osteokines and transforming growth factors before and after a single bout of plyometric exercise in child and adolescent females. Pediatr Exerc Sci. 2017;29(4):504–12. PubMed doi:10.1123/pes.2017-0042

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 9.

    Dennison EM, Harvey NC, Cooper C. Programming of osteoporosis and impact on osteoporosis risk. Clin Obstet Gynecol. 2013;56(3):549–55. PubMed doi:10.1097/GRF.0b013e31829cb9b0

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 10.

    Falk B, Haddad F, Klentrou P, Ward W, Kish K, Mezil Y, Radom-Aizik S. Differential sclerostin and parathyroid hormone response to exercise in boys and men. Osteoporos Int. 2016;27(3):1245–9. PubMed doi:10.1007/s00198-015-3310-z

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 11.

    Field A, Miles J. Discovering Statistics Using SAS. Thousand Oaks, CA: Sage; 2010.

  • 12.

    Fuchs RK, Bauer JJ, Snow CM. Jumping improves hip and lumbar spine bone mass in prepubescent children: a randomized controlled trial. J Bone Miner Res. 2001;16(1):148–56. PubMed doi:10.1359/jbmr.2001.16.1.148

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 13.

    Fujita KI, Janz S. Attenuation of WNT signaling by DKK-1 and -2 regulates BMP2-induced osteoblast differentiation and expression of OPG, RANKL and M-CSF. Mol Cancer. 2007;6(1):71. doi:10.1186/1476-4598-6-71

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 14.

    Kim CH, You L, Yellowley CE, Jacobs CR. Oscillatory fluid flow-induced shear stress decreases osteoclastogenesis through RANKL and OPG signaling. Bone. 2006;39(5):1043–7. PubMed doi:10.1016/j.bone.2006.05.017

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 15.

    Kim JH, Liu X, Wang J, et al. Wnt signaling in bone formation and its therapeutic potential for bone diseases. Ther Adv Musculoskelet Dis. 2013;5(1):13–31. PubMed doi:10.1177/1759720X12466608

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 16.

    Kirmani S, Amin S, McCready LK, Muller R, et al. Sclerostin levels during growth in children. Osteoporos Int. 2012;23(3):1123–30. PubMed doi:10.1007/s00198-011-1669-z

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 17.

    Kish K, Mezil Y, Ward WE, Klentrou P, Falk B. Effects of plyometric exercise session on markers of bone turnover in boys and young men. Eur J Appl Physiol. 2015;115(10):2115–24. PubMed doi:10.1007/s00421-015-3191-z

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 18.

    Klein-Nulend J, Bacabac RG, Bakker AD. Mechanical loading and how it affects bone cells: the role of the osteocyte cytoskeleton in maintaining our skeleton. Eur Cells Mater. 2012;24:278–91. PubMed doi:10.22203/eCM.v024a20

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 19.

    Kubota T, Michigami T, Ozono K. Wnt signaling in bone metabolism. J Bone Miner Metab. 2009;27(3):265–71. PubMed doi:10.1007/s00774-009-0064-8

  • 20.

    Lappe JM, Watson P, Gilsanz V, et al. The longitudinal effects of physical activity and dietary calcium on bone mass accrual across stages of pubertal development. J Bone Miner Res. 2015;30(1):156–64. PubMed doi:10.1002/jbmr.2319

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 21.

    Li X, Zhang Y, Kang H, et al. Sclerostin binds to LRP5/6 and antagonizes canonical Wnt signalling. J Biol Chem. 2005;280:19883–7. PubMed doi:10.1074/jbc.M413274200

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 22.

    Lucas R, Ramos E, Prata M, et al. Changes in serum RANKL and OPG with sexual development and their associations with bone turnover and bone mineral density in a cohort of girls. Clin Biochem. 2014;47(12):1040–6. PubMed doi:10.1016/j.clinbiochem.2014.04.012

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 23.

    Macias BR, Aspenberg P, Agholme F. Paradoxical Sost gene expression response to mechanical unloading in metaphyseal bone. Bone. 2013;53(2):515–9. PubMed doi:10.1016/j.bone.2013.01.018

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 24.

    Mackelvie KJ, McKay HA, Khan KM, Crocker PR. A school-based exercise intervention augments bone mineral accrual in early pubertal girls. J Pediatr. 2001;139(4):501–8. PubMed doi:10.1067/mpd.2001.118190

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 25.

    Maimoun L, Guillaume S, Lefebvre P, et al. Role of sclerostin and dickkopf-1 in the dramatic alteration in bone mass acquisition in adolescents and young women with recent anorexia nervosa. J Clin Endocrinol Metab. 2014;99(4):582–90. PubMed doi:10.1210/jc.2013-2565

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 26.

    Marques EA, Wanderley F, Machado L, et al. Effects of resistance and aerobic exercise on physical function, bone mineral density, OPG and RANKL in older women. Exp Gerontol. 2011;46(7):524–32. PubMed doi:10.1016/j.exger.2011.02.005

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 27.

    Mezil YA, Allison D, Kish K, et al. Response of bone turnover markers and cytokines to high-intensity low-impact exercise. Med Sci Sports Exerc. 2015;47(7):1495–502. PubMed doi:10.1249/MSS.0000000000000555

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 28.

    Mirwald RL, Baxter-Jones AD, Bailey DA, Beunen GP. An assessment of maturity from anthropometric measurements. Med Sci Sports Exerc. 2002;34(4):689–94. PubMed doi:10.1097/00005768-200204000-00020

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 29.

    Mirza FS, Padhi ID, Raisz LG, Lorenzo JA. Serum sclerostin levels negatively correlate with parathyroid hormone levels and free estrogen index in postmenopausal women. J Clin Endocrinol Metab. 2010;95:1991–7. doi:10.1210/jc.2009-2283

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 30.

    Miyagawa K, Kozai Y, Ito Y, et al. A novel underuse model shows that inactivity but not ovariectomy determines the deteriorated material properties and geometry of cortical bone in the tibia of adult rats. J Bone Miner Metab. 2011;29(4):422–36. PubMed doi:10.1007/s00774-010-0241-9

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 31.

    Modder UI, Hoey KA, Amin S, et al. Relation of age, gender, and bone mass to circulating sclerostin levels in women and men. J Bone Miner Res. 2011;26(2):373–9. PubMed doi:10.1002/jbmr.217

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 32.

    Moustafa A, Sugiyama T, Prasad J, Zaman G, Gross TS, Lanyon LE, Price JS. Mechanical loading-related changes in osteocyte sclerostin expression in mice are more closely associated with the subsequent osteogenic response than the peak strains engendered. Osteoporos Int. 2012;23(4):1225–34. PubMed doi:10.1007/s00198-011-1656-4

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 33.

    Pallant J. SPSS Survival Manual: A Step by Step Guide to Data Analysis Using SPSS. 4th ed. Crows Nest, Australia: Allen & Unwin; 2011.

  • 34.

    Pinzone JJ, Hall BM, Thudi NK, et al. The role of Dickkopf-1 in bone development, homeostasis, and disease. Blood. 2009;113(3):517–25. PubMed doi:10.1182/blood-2008-03-145169

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 35.

    Rahnert J, Fan X, Case N, Murphy TC, Grassi F, Sen B, Rubin J. The role of nitric oxide in the mechanical repression of RANKL in bone stromal cells. Bone. 2008;43(1):48–54. PubMed doi:10.1016/j.bone.2008.03.006

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 36.

    Robling AG, Niziolek PJ, Baldridge LA, et al. Mechanical stimulation of bone in vivo reduces osteocyte expression of Sost/sclerostin. J Biol Chem. 2008;283(9):5866–75. PubMed doi:10.1074/jbc.M705092200

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 37.

    Sapir-Koren R, Livshits G. Osteocyte control of bone remodeling: is sclerostin a key molecular coordinator of the balanced bone resorption-formation cycles? Osteoporos Int. 2014;25(12):2685–700. PubMed doi:10.1007/s00198-014-2808-0

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 38.

    Spatz JM, Wein MN, Gooi JH, et al. The Wnt inhibitor sclerostin is up-regulated by mechanical unloading in osteocytes in vitro. J Biol Chem. 2015;290(27):16744–58. PubMed doi:10.1074/jbc.M114.628313

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 39.

    Specker B, Thiex NW, Sudhagoni RG. Does exercise influence pediatric bone? A systematic review. Clin Orthop Relat Res. 2015;473(11):3658–72. PubMed doi:10.1007/s11999-015-4467-7

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 40.

    Suen PK, Qin L. Sclerostin, an emerging therapeutic target for treating osteoporosis and osteoporotic fracture: a general review. J Orthop Transl. 2016;4:1–13. doi:10.1016/j.jot.2015.08.004

    • Search Google Scholar
    • Export Citation
  • 41.

    van Bezooijen RL, Roelen BA, Visser A, et al. Sclerostin is an osteocyte-expressed negative regulator of bone formation, but not a classical BMP antagonist. J Exp Med. 2004;199(6):805–14. PubMed doi:10.1084/jem.20031454

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 42.

    Weivoda MM, Oursler MJ. Developments in sclerostin biology: regulation of gene expression, mechanisms of action, and physiological functions. Curr Osteoporos Rep. 2014;12(1):107–14. PubMed doi:10.1007/s11914-014-0188-1

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 43.

    Wijenayaka AR, Kogawa M, Lim HP, Bonewald LF, Findlay DM, Atkins GJ. Sclerostin stimulates osteocyte support of osteoclast activity by a RANKL-dependent pathway. PLoS ONE. 2011;6(10):e25900. PubMed doi:10.1371/journal.pone.0025900

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
All Time Past Year Past 30 Days
Abstract Views 73 72 14
Full Text Views 3 3 2
PDF Downloads 2 2 1