Wnt Signaling–Related Osteokines and Transforming Growth Factors Before and After a Single Bout of Plyometric Exercise in Child and Adolescent Females

in Pediatric Exercise Science
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This study examined resting levels of catabolic and anabolic osteokines related to Wnt signaling and their responses to a single bout of plyometric exercise in child and adolescent females. Fourteen premenarcheal girls [10.5 (1.8) y old] and 12 postmenarcheal adolescent girls [15.0 (1.0) y old] performed a plyometric exercise trial. One resting and 3 postexercise blood samples (5 min, 1 h, and 24 h postexercise) were analyzed for sclerostin, dickkopf-1 (DKK-1), osteoprotegerin (OPG), receptor activator of nuclear factor kappa-β ligand (RANKL), and transforming growth factors (TGF-β1, TGF-β2, and TGF-β3). Premenarcheal girls had significantly higher resting sclerostin, TGF-β1, TGF-β2, and TGF-β3 than the postmenarcheal girls, with no significant time effect or group-by-time interaction. DKK-1 was higher in premenarcheal compared with postmenarcheal girls. There was an overall significant DKK-1 decrease from baseline to 1 h postexercise, which remained lower than baseline 24 h postexercise in both groups. There was neither a significant group effect nor group-by-time interaction in OPG, RANKL, and their ratio. RANKL decreased 5 min postexercise compared with baseline and remained significantly lower from baseline 24 h following the exercise. No changes were observed in OPG. OPG/RANKL ratio was significantly elevated compared with resting values 1 h postexercise. In young females, high-impact exercise induces an overall osteogenic effect through a transitory suppression of catabolic osteokines up to 24 h following exercise.

Dekker, Nelson, Kurgan, Falk, Josse, and Klentrou are with the Dept. of Kinesiology, Brock University, St. Catharines, Ontario, Canada.

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

    Abed E, Couchourel D, Delalandre A, et al. Low sirtuin 1 levels in human osteoarthritis subchondral osteoblasts lead to abnormal sclerostin expression which decreases Wnt/β-catenin activity. Bone. 2014;59:2836. PubMed doi:10.1016/j.bone.2013.10.020

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

    An J, Yang H, Zhang Q, et al. Natural products for treatment of osteoporosis: the effects and mechanisms on promoting osteoblast-mediated bone formation. Life Sci. 2016;147:4658. PubMed doi:10.1016/j.lfs.2016.01.024

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 3.

    Banfi G, Lombardi G, Colombini A, Lippi G. Bone metabolism markers in sports medicine. Sports Med. 2010;40(8):697714. doi:10.2165/11533090-000000000-00000

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

    Conti P, Theoharides TC, Cerulli G. Impact of cytokines on bone homeostasis. J Orthop. 2014;6(3):938.

  • 5.

    Cullen KW, Watson K, Zakeri I. Relative reliability and validity of the Block Kids Questionnaire among youth aged 10 to 17 years. J Am Diet Assoc. 2008;108(5):8626. PubMed doi:10.1016/j.jada.2008.02.015

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 6.

    Edwards JR, Nyman JS, Lwin ST, et al. Inhibition of TGF-β signaling by 1D11 antibody treatment increases bone mass and quality in vivo. J Bone Miner Res. 2010;25(11):241926. PubMed doi:10.1002/jbmr.139

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

    Falk B, Haddad F, Klentrou P, et al. Differential sclerostin and parathyroid hormone response to exercise in boys and men. Osteoporosis Int. 2016;27(3):12459. doi:10.1007/s00198-015-3310-z

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 8.

    Fazeli PK, Ackerman KE, Pierce L, Guereca G, Bouxsein M, Misra M. Sclerostin and Pref-1 have differential effects on bone mineral density and strength parameters in adolescent athletes compared with non-athletes. Osteoporosis Int. 2013;24(9):243340. doi:10.1007/s00198-013-2353-2

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

    Godin G, Shephard RJ. A simple method to assess exercise behavior in the community. Can J Appl Sport Sci. 1985;10(3):1416. PubMed

  • 10.

    Gombos GC, Bajsz V, Pek E, et al. Direct effects of physical training on markers of bone metabolism and serum sclerostin concentrations in older adults with low bone mass. BMC Musculoskelet Disord. 2016;17:254. PubMed doi:10.1186/s12891-016-1109-5

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

    Guerrero F, Herencia C, Almaden Y, et al. TGF-β prevents phosphate-induced osteogenesis through inhibition of BMP and Wnt/β-catenin pathways. PLoS One. 2014;9(2):89179. PubMed doi:10.1371/journal.pone.0089179

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 12.

    Jilka RL, O’Brien CA. The role of osteocytes in age-related bone loss. Curr Osteoporos Rep. 2016;14(1):1625. PubMed doi:10.1007/s11914-016-0297-0

  • 13.

    Johnson ML, Harnish K, Nusse R, Van Hul W. LRP5 and Wnt signaling: a union made for bone. J Bone Miner Res. 2004;19(11):174957. PubMed doi:10.1359/JBMR.040816

  • 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):10437. PubMed doi:10.1016/j.bone.2006.05.017

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

    Kirmani S, Amin S, McCready LK, et al. Sclerostin levels during growth in children. Osteoporos Int. 2012;23(3):112330. PubMed doi:10.1007/s00198-011-1669-z

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

    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):211524. PubMed doi:10.1007/s00421-015-3191-z

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

    Krishnan V, Bryant HU, Macdougald OA. Regulation of bone mass by Wnt signaling. J Clin Invest. 2006;116(5):12029. PubMed doi:10.1172/JCI28551

  • 18.

    Logan CY, Nusse R. The Wnt signaling pathway in development and disease. Annu Rev Cell Dev Biol. 2004;20:781810. PubMed doi:10.1146/annurev.cellbio.20.010403.113126

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

    Loots GG, Keller H, Leupin O, Murugesh D, Collette NM, Genetos DC. TGF-β regulates sclerostin expression via the ECR5 enhancer. Bone. 2012;50(3):6639. PubMed doi:10.1016/j.bone.2011.11.016

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 20.

    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):10406. doi:10.1016/j.clinbiochem.2014.04.012

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

    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):5018. PubMed doi:10.1067/mpd.2001.118190

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

    Manolagas SC. Wnt signaling and osteoporosis. Maturitas. 2014;78(3):2337. PubMed doi:10.1016/j.maturitas.2014.04.013

  • 23.

    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):52432. PubMed doi:10.1016/j.exger.2011.02.005

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

    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):1495502. PubMed doi:10.1249/MSS.0000000000000555

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

    Mirwald RL, Baxter-Jones AD, Bailey DA, Beunen GP. An assessment of maturity from anthropometric measurements. Med Sci Sports Exerc. 2002;34(4):68994. PubMed

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

    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(4): 19917. PubMed doi:10.1210/jc.2009-2283

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

    Mora S, Puzzovio M, Giacomet V, et al. Sclerostin and DKK-1: two important regulators of bone metabolism in HIV-infected youths. Endocrine. 2015;49(3):78390. PubMed doi:10.1007/s12020-015-0527-8

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

    Niu T, Rosen CJ. The insulin-like growth factor-I gene and osteoporosis: a critical appraisal. Gene. 2005;361:3856. PubMed doi:10.1016/j.gene.2005.07.016

  • 29.

    Patil AS, Sable RB, Kothari RM. An update on transforming growth factor-β (TGF-β): sources, types, functions and clinical applicability for cartilage/bone healing. J Cell Physiol. 2011;226(12):3094103. PubMed doi:10.1002/jcp.22698

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

    Pinzone JJ, Hall BM, Thudi NK, et al. The role of Dickkopf-1 in bone development, homeostasis, and disease. Blood. 2009;113(3):51725. PubMed doi:10.1182/blood-2008-03-145169

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

    Radetti G, Franceschi R, Adami S, Longhi S, Rossini M, Gatti D. Higher circulating parathormone is associated with smaller and weaker bones in obese children. Calcif Tissue Int. 2014;95(1):17. PubMed doi:10.1007/s00223-014-9853-8

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

    Ripamonti U, Duarte R, Ferretti C. Re-evaluating the induction of bone formation in primates. Biomaterials. 2014;35(35):940722. PubMed doi:10.1016/j.biomaterials.2014.07.053

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

    Ripamonti U, Roden LC. Induction of bone formation by transforming growth factor-β2 in the non-human primate Papio ursinus and its modulation by skeletal muscle responding stem cells. Cell Prolif. 2010;43(3):20718. PubMed doi:10.1111/j.1365-2184.2010.00675.x

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 34.

    Robinson JA, Chatterjee-Kishore M, Yaworsky PJ, et al. Wnt/beta-catenin signaling is a normal physiological response to mechanical loading in bone. J Biol Chem. 2006;281(42):317208. PubMed doi:10.1074/jbc.M602308200

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

    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):586675. PubMed doi:10.1074/jbc.M705092200

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

    Rubin J, Murphy TC, Zhu L, Roy E, Nanes MS, Fan X. Mechanical strain differentially regulates endothelial nitric-oxide synthase and receptor activator of nuclear kappa B ligand expression via ERK1/2 MAPK. J Biol Chem. 2003;278(36):3401825. PubMed doi:10.1074/jbc.M302822200

    • Search Google Scholar
    • Export Citation
  • 37.

    Sallis JF, Buono MJ, Roby JJ, Micale FG, Nelson JA. Seven-day recall and other physical activity self-reports in children and adolescents. Med Sci Sports Exerc. 1993;25(1):99108. PubMed doi:10.1249/00005768-199301000-00014

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

    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):2685700. PubMed doi:10.1007/s00198-014-2808-0

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

    Subar AF, Thompson FE, Kipnis V, et al. Comparative validation of the Block, Willett, and National Cancer Institute food frequency questionnaires: the Eating at America’s Table Study. Am J Epidemiol. 2001;154(12):108999. PubMed doi:10.1093/aje/154.12.1089

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

    Tanner JM. Growth at Adolescence. 2nd ed. Oxford, UK: Blackwell Scientific Publications; 1962.

  • 41.

    Westendorf JJ, Kahler RA, Schroeder TM. Wnt signaling in osteoblasts and bone diseases. Gene. 2004;341:1939. PubMed doi:10.1016/j.gene.2004.06.044

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