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Muscle-Bone Crosstalk in Chronic Kidney Disease: The Potential Modulatory Effects of Exercise

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Abstract

Chronic kidney disease (CKD) is a prevalent worldwide public burden that increasingly compromises overall health as the disease progresses. Two of the most negatively affected tissues are bone and skeletal muscle, with CKD negatively impacting their structure, function and activity, impairing the quality of life of these patients and contributing to morbidity and mortality. Whereas skeletal health in this population has conventionally been associated with bone and mineral disorders, sarcopenia has been observed to impact skeletal muscle health in CKD. Indeed, bone and muscle tissues are linked anatomically and physiologically, and together regulate functional and metabolic mechanisms. With the initial crosstalk between the skeleton and muscle proposed to explain bone formation through muscle contraction, it is now understood that this communication occurs through the interaction of myokines and osteokines, with the skeletal muscle secretome playing a pivotal role in the regulation of bone activity. Regular exercise has been reported to be beneficial to overall health. Also, the positive regulatory effect that exercise has been proposed to have on bone and muscle anatomical, functional, and metabolic activity has led to the proposal of regular physical exercise as a therapeutic strategy for muscle and bone-related disorders. The detection of bone- and muscle-derived cytokine secretion following physical exercise has strengthened the idea of a cross communication between these organs. Hence, this review presents an overview of the impact of CKD in bone and skeletal muscle, and narrates how these tissues intrinsically communicate with each other, with focus on the potential effect of exercise in the modulation of this intercommunication.

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References

  1. Stenvinkel P, Larsson TE (2013) Chronic kidney disease: a clinical model of premature aging. Am J Kidney Dis 62:339–351

    PubMed  Google Scholar 

  2. Kooman JP, Kotanko P, Schols AMWJ, Shiels PG, Stenvinkel P (2014) Chronic kidney disease and premature ageing. Nat Rev Nephrol 10:732–742

    CAS  PubMed  Google Scholar 

  3. Moe S, Drüeke T, Cunningham J, Goodman W, Martin K, Olgaard K, Ott S, Sprague S, Lameire N, Eknoyan G (2006) Definition, evaluation, and classification of renal osteodystrophy: a position statement from kidney disease: improving global outcomes (KDIGO). Kidney Int 69:1945–1953

    CAS  PubMed  Google Scholar 

  4. Pimentel A, Ureña-Torres P, Zillikens MC, Bover J, Cohen-Solal M (2017) Fractures in patients with CKD—diagnosis, treatment, and prevention: a review by members of the European calcified tissue society and the European renal association of nephrology dialysis and transplantation. Kidney Int 92:1343–1355

    PubMed  Google Scholar 

  5. Gansevoort RT, Correa-Rotter R, Hemmelgarn BR, Jafar TH, Heerspink HJL, Mann JF, Matsushita K, Wen CP (2013) Chronic kidney disease and cardiovascular risk: epidemiology, mechanisms, and prevention. Lancet 382:339–352

    PubMed  Google Scholar 

  6. Moorthi RN, Avin KG (2017) Clinical relevance of sarcopenia in chronic kidney disease. Curr Opin Nephrol Hypertens 26:219–228

    PubMed  PubMed Central  Google Scholar 

  7. Avin KG, Moorthi RN (2015) Bone is not alone: the effects of skeletal muscle dysfunction in chronic kidney disease. Curr Osteoporos Rep 13:173–179

    PubMed  PubMed Central  Google Scholar 

  8. Zelle DM, Klaassen G, Van Adrichem E, Bakker SJL, Corpeleijn E, Navis G (2017) Physical inactivity: a risk factor and target for intervention in renal care. Nat Rev Nephrol 13:152–168

    PubMed  Google Scholar 

  9. Ortiz A, Sanchez-Niño MD (2019) Sarcopenia in CKD: a roadmap from basic pathogenetic mechanisms to clinical trials. Clin Kidney J 12:110–112

    PubMed  PubMed Central  Google Scholar 

  10. De Souza VA, Oliveira D, Barbosa SR, Corrêa JODA, Colugnati FAB, Mansur HN, Fernandes NMDS, Bastos MG (2017) Sarcopenia in patients with chronic kidney disease not yet on dialysis: analysis of the prevalence and associated factors. PLoS ONE 12:e0176230

    PubMed  PubMed Central  Google Scholar 

  11. Hirakawa Y, Jao TM, Inagi R (2017) Pathophysiology and therapeutics of premature ageing in chronic kidney disease, with a focus on glycative stress. Clin Exp Pharmacol Physiol 44:70–77

    CAS  PubMed  Google Scholar 

  12. Tagliaferri C, Wittrant Y, Davicco MJ, Walrand S, Coxam V (2015) Muscle and bone, two interconnected tissues. Ageing Res Rev 21:55–70

    CAS  PubMed  Google Scholar 

  13. Ferretti JL, Capozza RF, Cointry GR, García SL, Plotkin H, Filgueira MLA, Zanchetta JR (1998) Gender-related differences in the relationship between densitometric values of whole-body bone mineral content and lean body mass in humans between 2 and 87 years of age. Bone 22:683–690

    CAS  PubMed  Google Scholar 

  14. Hamrick MW (2012) The skeletal muscle secretome: an emerging player in muscle–bone crosstalk. Bonekey Rep 1:60

    PubMed  PubMed Central  Google Scholar 

  15. Kirk B, Feehan J, Lombardi G, Duque G (2020) Muscle, bone, and fat crosstalk: the biological role of myokines, osteokines, and adipokines. Curr Osteoporos Rep 184:388–400

    Google Scholar 

  16. Huxley HE (1969) The mechanism of muscular contraction. Science 164:1356–1365

    CAS  PubMed  Google Scholar 

  17. Colaianni G, Mongelli T, Colucci S, Cinti S, Grano M (2016) Crosstalk between muscle and bone via the muscle-myokine irisin. Curr Osteoporos Rep 14:132–137

    CAS  PubMed  Google Scholar 

  18. Wolfe RR (2006) The underappreciated role of muscle in health and disease. Am J Clin Nutr 84:475–482

    CAS  PubMed  Google Scholar 

  19. Trajanoska K, Rivadeneira F, Kiel DP, Karasik D (2019) Genetics of bone and muscle interactions in humans. Curr Osteoporos Rep 17:86–95

    PubMed  PubMed Central  Google Scholar 

  20. Riley LA, Esser KA (2017) The role of the molecular clock in skeletal muscle and what it is teaching us about muscle-bone crosstalk. Curr Osteoporos Rep 15:222–230

    PubMed  PubMed Central  Google Scholar 

  21. Naylor KL, Garg AX, Zou G et al (2015) Comparison of fracture risk prediction among individuals with reduced and normal kidney function. Clin J Am Soc Nephrol 10:646–653

    PubMed  PubMed Central  Google Scholar 

  22. Honma M, Ikebuchi Y, Kariya Y, Suzuki H (2014) Regulatory mechanisms of RANKL presentation to osteoclast precursors. Curr Osteoporos Rep 12:115–120

    PubMed  Google Scholar 

  23. Drüeke TB, Massy ZA (2016) Changing bone patterns with progression of chronic kidney disease. Kidney Int 89:289–302

    PubMed  Google Scholar 

  24. Hou Y-C, Lu C-L, Lu K-C (2018) Mineral bone disorders in chronic kidney disease. Nephrology 23:88–94

    CAS  PubMed  Google Scholar 

  25. Levin A, Bakris GL, Molitch M, Smulders M, Tian J, Williams LA, Andress DL (2007) Prevalence of abnormal serum vitamin D, PTH, calcium, and phosphorus in patients with chronic kidney disease: results of the study to evaluate early kidney disease. Kidney Int 71:31–38

    CAS  PubMed  Google Scholar 

  26. Moranne O, Froissart M, Rossert J et al (2009) Timing of onset of CKD-related metabolic complications. J Am Soc Nephrol 20:164–171

    PubMed  PubMed Central  Google Scholar 

  27. Sprague SM, Bellorin-Font E, Jorgetti V et al (2016) Diagnostic accuracy of bone turnover markers and bone histology in patients with CKD treated by dialysis. Am J Kidney Dis 67:559–566

    PubMed  Google Scholar 

  28. Malluche HH, Mawad HW, Monier-Faugere MC (2011) Renal osteodystrophy in the first decade of the new millennium: analysis of 630 bone biopsies in black and white patients. J Bone Miner Res 26(13):68–1376

    Google Scholar 

  29. Nickolas TL, Stein EM, Dworakowski E et al (2013) Rapid cortical bone loss in patients with chronic kidney disease. J Bone Miner Res 28:1811–1820

    CAS  PubMed  Google Scholar 

  30. Udagawa N, Takahashi N, Katagiri T et al (1995) Interleukin (IL)-6 induction of osteoclast differentiation depends on IL-6 receptors expressed on osteoblastic cells but not on osteoclast progenitors. J Exp Med 182:1461–1468

    CAS  PubMed  Google Scholar 

  31. Takarada T, Xu C, Ochi H et al (2017) Bone resorption is regulated by circadian clock in osteoblasts. J Bone Miner Res 32:872–881

    CAS  PubMed  Google Scholar 

  32. Lacey DL, Boyle WJ, Simonet WS, Kostenuik PJ, Dougall WC, Sullivan JK, Martin JS, Dansey R (2012) Bench to bedside: elucidation of the OPG-RANK-RANKL pathway and the development of denosumab. Nat Rev Drug Discov 11:401–419

    CAS  PubMed  Google Scholar 

  33. Ominsky MS, Li X, Asuncion FJ et al (2008) RANKL inhibition with osteoprotegerin increases bone strength by improving cortical and trabecular bone architecture in ovariectomized rats. J Bone Miner Res 23:672–682

    CAS  PubMed  Google Scholar 

  34. Doumouchtsis KK, Kostakis AI, Doumouchtsis SK, Tziamalis MP, Tsigris C, Kostaki MA, Perrea DN (2007) sRANKL/osteoprotegerin complex and biochemical markers in a cohort of male and female hemodialysls patients. J Endocrinol Invest 30:762–766

    CAS  PubMed  Google Scholar 

  35. Kazama JJ, Shigematsu T, Yano K, Tsuda E, Miura M, Iwasaki Y, Kawaguchi Y, Gejyo F, Kurokawa K, Fukagawa M (2002) Increased circulating levels of osteoclastogenesis inhibitory factor (osteoprotegerin) in patients with chronic renal failure. Am J Kidney Dis 39:525–532

    CAS  PubMed  Google Scholar 

  36. Avbersek-Luznik I, Malesic I, Rus I, Marc J (2002) Increased levels of osteoprotegerin in hemodialysis patients. Clin Chem Lab Med 40:1019–1023

    CAS  PubMed  Google Scholar 

  37. Avbersek-Luznik I, Balon BP, Rus I, Marc J (2005) Increased bone resorption in HD patients: is it caused by elevated RANKL synthesis? Nephrol Dial Transplant 20:566–570

    CAS  PubMed  Google Scholar 

  38. Albalate M, de la Piedra C, Fernández C, Lefort M, Santana H, Hernando P, Hernández J, Caramelo C (2006) Association between phosphate removal and markers of bone turnover in haemodialysis patients. Nephrol Dial Transplant 21:1626–1632

    CAS  PubMed  Google Scholar 

  39. Kazama JJ, Kato H, Sato T, Shigematsu T, Fukagawa M, Iwasaki Y, Gejyo F (2002) Circulating osteoprotegerin is not removed through haemodialysis membrane. Nephrol Dial Transplant 17:1860–1861

    CAS  PubMed  Google Scholar 

  40. Razzaque MS (2011) Osteocalcin: a pivotal mediator or an innocent bystander in energy metabolism? Nephrol Dial Transplant 26:42–45

    CAS  PubMed  Google Scholar 

  41. Delmas PD, Wilson DM, Mann KG, Riggs BL (1983) Effect of renal function on plasma levels of bone gla-protein. J Clin Endocrinol Metab 57:1028–1030

    CAS  PubMed  Google Scholar 

  42. Coen G, Mazzaferro S, Bonucci E, Taggi F, Ballanti P, Bianchi AR, Donato G, Massimetti C, Smacchi A, Cinotti GA (1985) Bone GLA protein in predialysis chronic renal failure. Effects of 1,25 (OH)2D3 administration in a long-term follow-up. Kidney Int 28:783–790

    CAS  PubMed  Google Scholar 

  43. Zhang M, Ni Z, Zhou W, Qian J (2015) Undercarboxylated osteocalcin as a biomarker of subclinical atherosclerosis in non-dialysis patients with chronic kidney disease. J Biomed Sci 22:75

    PubMed  PubMed Central  Google Scholar 

  44. Quarles LD (2012) Role of FGF23 in vitamin D and phosphate metabolism: implications in chronic kidney disease. Exp Cell Res 318:1040–1048

    CAS  PubMed  PubMed Central  Google Scholar 

  45. Lara-Castillo N, Johnson ML (2020) Bone-muscle mutual interactions. Curr Osteoporos Rep 18:408–421

    PubMed  PubMed Central  Google Scholar 

  46. Kido S, Hashimoto Y, Segawa H, Tatsumi S, Miyamoto K (2012) Muscle atrophy in patients wirh ckd results from fgf23/klotho-mediated supression of insulin/igf-i signaling. Kidney Res Clin Pract 31:A44

    Google Scholar 

  47. Avin KG, Vallejo JA, Chen NX, Wang K, Touchberry CD, Brotto M, Dallas SL, Moe SM, Wacker MJ (2018) Fibroblast growth factor 23 does not directly influence skeletal muscle cell proliferation and differentiation or ex vivo muscle contractility. Am J Physiol - Endocrinol Metab 315:E594–E604

    CAS  PubMed  PubMed Central  Google Scholar 

  48. Koppe L, Fouque D, Kalantar-Zadeh K (2019) Kidney cachexia or protein-energy wasting in chronic kidney disease: facts and numbers. J Cachexia Sarcopenia Muscle 10:479–484

    PubMed  PubMed Central  Google Scholar 

  49. Jadeja YP, Kher V (2012) Protein energy wasting in chronic kidney disease: an update with focus on nutritional interventions to improve outcomes. Indian J Endocrinol Metab 16:246–251

    CAS  PubMed  PubMed Central  Google Scholar 

  50. Wang XH, Mitch WE (2014) Mechanisms of muscle wasting in chronic kidney disease. Nat Rev Nephrol 10:504–516

    CAS  PubMed  PubMed Central  Google Scholar 

  51. Stenvinkel P, Lindholm B, Heimbürger O (2004) Novel approaches in an integrated therapy of inflammatory-associated wasting in end-stage renal disease. Semin Dial 17:505–515

    PubMed  Google Scholar 

  52. Roshanravan B, Gamboa J, Wilund K (2017) Exercise and CKD: skeletal muscle dysfunction and practical application of exercise to prevent and treat physical impairments in CKD. Am J Kidney Dis 69:837–852

    PubMed  PubMed Central  Google Scholar 

  53. Beddhu S, Chen X, Wei G, Raj D, Raphael KL, Boucher R, Chonchol MB, Murtaugh MA, Greene T (2017) Associations of protein−energy wasting syndrome criteria with body composition and mortality in the general and moderate chronic kidney disease populations in the United States. Kidney Int Reports 2:390–399

    Google Scholar 

  54. Moreau-Gaudry X, Jean G, Genet L, Lataillade D, Legrand E, Kuentz F, Fouque D (2014) A simple protein-energy wasting score predicts survival in maintenance hemodialysis patients. J Ren Nutr 24:395–400

    PubMed  Google Scholar 

  55. Rolland Y, Van Kan GA, Gillette-Guyonnet S, Vellas B (2011) Cachexia versus sarcopenia. Curr Opin Clin Nutr Metab Care 14:15–21

    PubMed  Google Scholar 

  56. Santilli V, Bernetti A, Mangone M, Paoloni M (2014) Clinical definition of sarcopenia. Clin Cases Miner Bone Metab 11:177–180

    PubMed  PubMed Central  Google Scholar 

  57. Clark BC, Manini TM (2012) What is dynapenia? Nutrition 28:495–503

    PubMed  PubMed Central  Google Scholar 

  58. Delmonico MJ, Harris TB, Visser M et al (2009) Longitudinal study of muscle strength, quality, and adipose tissue infiltration. Am J Clin Nutr 90:1579–1585

    CAS  PubMed  PubMed Central  Google Scholar 

  59. McPherron AC, Guo T, Bond ND, Gavrilova O (2013) Increasing muscle mass to improve metabolism. Adipocyte 2:92–98

    CAS  PubMed  PubMed Central  Google Scholar 

  60. Argilés JM, Campos N, Lopez-Pedrosa JM, Rueda R, Rodriguez-Mañas L (2016) Skeletal muscle regulates metabolism via interorgan crosstalk: roles in health and disease. J Am Med Dir Assoc 17:789–796

    PubMed  Google Scholar 

  61. Meyer C, Dostou JM, Welle SL, Gerich JE (2002) Role of human liver, kidney, and skeletal muscle in postprandial glucose homeostasis. Am J Physiol - Endocrinol Metab 282:E419-427

    CAS  PubMed  Google Scholar 

  62. Zurlo F, Larson K, Bogardus C, Ravussin E (1990) Skeletal muscle metabolism is a major determinant of resting energy expenditure. J Clin Invest 86:1423–1427

    CAS  PubMed  PubMed Central  Google Scholar 

  63. Huang JW, Lien YC, Wu HY, Yen CJ, Pan CC, Hung TW, Su CT, Chiang CK, Cheng HT, Hung KY (2013) Lean body mass predicts long-term survival in Chinese patients on peritoneal dialysis. PLoS ONE 8:e54976

    CAS  PubMed  PubMed Central  Google Scholar 

  64. Holwerda AM, Paulussen KJM, Overkamp M, Smeets JSJ, Gijsen AP, Goessens JPB, Verdijk LB, Van Loon LJC (2018) Daily resistance-type exercise stimulates muscle protein synthesis in vivo in young men. J Appl Physiol 124:66–75

    CAS  PubMed  Google Scholar 

  65. Glass DJ (2005) Skeletal muscle hypertrophy and atrophy signaling pathways. Int J Biochem Cell Biol 37:1974–1984

    CAS  PubMed  Google Scholar 

  66. Sandri M (2008) Signaling in muscle atrophy and hypertrophy. Physiology 23:160–170

    CAS  PubMed  Google Scholar 

  67. Burd NA, De Lisio M (2017) Skeletal muscle remodeling: interconnections between stem cells and protein turnover. Exerc Sport Sci Rev 45:187–191

    PubMed  Google Scholar 

  68. van Vliet S, Skinner SK, Beals JW et al (2018) Dysregulated handling of dietary protein and muscle protein synthesis after mixed-meal ingestion in maintenance hemodialysis patients. Kidney Int Reports 3:1403–1415

    Google Scholar 

  69. Draicchio F, van Vliet S, Ancu O et al (2020) Integrin-associated ILK and PINCH1 protein content are reduced in skeletal muscle of maintenance hemodialysis patients. J Physiol. https://doi.org/10.1113/JP280441

    Article  PubMed  Google Scholar 

  70. Baker LA, O’Sullivan TF, Robinson KA, Redshaw Z, Graham Brown M, Ashford RU, Smith AC, Watson EL (2020) Establishment and characterisation of primary skeletal muscle cell cultures from patients with advanced chronic kidney disease. BioRxiv. https://doi.org/10.1101/2020.11.16.384263

    Article  PubMed  PubMed Central  Google Scholar 

  71. Schwartz AL, Ciechanover A (2009) Targeting proteins for destruction by the ubiquitin system: implications for human pathobiology. Annu Rev Pharmacol Toxicol 49:73–96

    CAS  PubMed  Google Scholar 

  72. Cocchiaro P, De Pasquale V, Della MR, Tafuri S, Avallone L, Pizard A, Moles A, Pavone LM (2017) The multifaceted role of the lysosomal protease cathepsins in kidney disease. Front Cell Dev Biol 5:114

    PubMed  PubMed Central  Google Scholar 

  73. Lilienbaum A (2013) Relationship between the proteasomal system and autophagy. Int J Biochem Mol Biol 4:1–26

    CAS  PubMed  PubMed Central  Google Scholar 

  74. Su Z, Klein JD, Du J, Franch HA, Zhang L, Hassounah F, Hudson MB, Wang XH (2017) Chronic kidney disease induces autophagy leading to dysfunction of mitochondria in skeletal muscle. Am J Physiol - Ren Physiol 312:F1128–F1140

    CAS  Google Scholar 

  75. Sandri M (2011) New findings of lysosomal proteolysis in skeletal muscle. Curr Opin Clin Nutr Metab Care 14:223–229

    CAS  PubMed  Google Scholar 

  76. O’Sullivan T, Smith AC, Watson EL (2018) Satellite cell function, intramuscular inflammation and exercise in chronic kidney disease. Clin Kidney J 11:810–821

    PubMed  PubMed Central  Google Scholar 

  77. Elkasrawy MN, Hamrick MW (2010) Myostatin (GDF-8) as a key factor linking muscle mass and bone structure. J Musculoskelet Neuronal Interact 10:56–63

    CAS  PubMed  Google Scholar 

  78. Huang Z, Chen D, Zhang K, Yu B, Chen X, Meng J (2007) Regulation of myostatin signaling by c-Jun N-terminal kinase in C2C12 cells. Cell Signal 19:2286–2295

    CAS  PubMed  Google Scholar 

  79. Bataille S, Chauveau P, Fouque D, Aparicio M, Koppe L (2020) Myostatin and muscle atrophy during chronic kidney disease. Nephrol Dial Transplant. https://doi.org/10.1093/ndt/gfaa129

    Article  PubMed  Google Scholar 

  80. Verzola D, Procopio V, Sofia A et al (2011) Apoptosis and myostatin mRNA are upregulated in the skeletal muscle of patients with chronic kidney disease. Kidney Int 79:773–782

    CAS  PubMed  Google Scholar 

  81. Zhang L, Rajan V, Lin E et al (2011) Pharmacological inhibition of myostatin suppresses systemic inflammation and muscle atrophy in mice with chronic kidney disease. FASEB J 25:1653–1663

    CAS  PubMed  PubMed Central  Google Scholar 

  82. Zhang L, Pan J, Dong Y, Tweardy DJ, Dong Y, Garibotto G, Mitch WE (2013) Stat3 activation links a C/EBPδ to myostatin pathway to stimulate loss of muscle mass. Cell Metab 18:368–379

    CAS  PubMed  PubMed Central  Google Scholar 

  83. Muñoz-Cánoves P, Scheele C, Pedersen BK, Serrano AL (2013) Interleukin-6 myokine signaling in skeletal muscle: a double-edged sword? FEBS J 280:4131–4138

    PubMed  PubMed Central  Google Scholar 

  84. Serrano AL, Baeza-Raja B, Perdiguero E, Jardí M, Muñoz-Cánoves P (2008) Interleukin-6 is an essential regulator of satellite cell-mediated skeletal muscle hypertrophy. Cell Metab 7:33–44

    CAS  PubMed  Google Scholar 

  85. Stenvinkel P, Ketteler M, Johnson RJ, Lindholm B, Pecoits-Filho R, Riella M, Heimbürger O, Cederholm T, Girndt M (2005) IL-10, IL-6, and TNF-α: central factors in the altered cytokine network of uremia - the good, the bad, and the ugly. Kidney Int 67:1216–1233

    CAS  PubMed  Google Scholar 

  86. Garibotto G, Sofia A, Procopio V et al (2006) Peripheral tissue release of interleukin-6 in patients with chronic kidney diseases: effects of end-stage renal disease and microinflammatory state. Kidney Int 70:384–390

    CAS  PubMed  Google Scholar 

  87. Hamrick MW, Shi X, Zhang W, Pennington C, Thakore H, Haque M, Kang B, Isales CM, Fulzele S, Wenger KH (2007) Loss of myostatin (GDF8) function increases osteogenic differentiation of bone marrow-derived mesenchymal stem cells but the osteogenic effect is ablated with unloading. Bone 40:1544–1553

    CAS  PubMed  PubMed Central  Google Scholar 

  88. Qin Y, Peng Y, Zhao W et al (2017) Myostatin inhibits osteoblastic differentiation by suppressing osteocyte-derived exosomal microRNA-218: a novel mechanism in muscle-bone communication. J Biol Chem 292:11021–11033

    CAS  PubMed  PubMed Central  Google Scholar 

  89. Lyu H, Xiao Y, Guo Q, Huang Y, Luo X (2020) The role of bone-derived exosomes in regulating skeletal metabolism and extraosseous diseases. Front Cell Dev Biol 8:89

    PubMed  PubMed Central  Google Scholar 

  90. DiGirolamo DJ, Mukherjee A, Fulzele K, Gan Y, Cao X, Frank SJ, Clemens TL (2007) Mode of growth hormone action in osteoblasts. J Biol Chem 282:31666–31674

    CAS  PubMed  Google Scholar 

  91. Adhikary S, Choudhary D, Tripathi AK, Karvande A, Ahmad N, Kothari P, Trivedi R (2019) FGF-2 targets sclerostin in bone and myostatin in skeletal muscle to mitigate the deleterious effects of glucocorticoid on musculoskeletal degradation. Life Sci 229:261–276

    CAS  PubMed  Google Scholar 

  92. Quinn LS, Anderson BG, Strait-Bodey L, Stroud AM, Argués JM (2009) Oversecretion of interleukin-15 from skeletal muscle reduces adiposity. Am J Physiol - Endocrinol Metab 296:E191-202

    CAS  PubMed  Google Scholar 

  93. Mansouri L, Paulsson JM, Moshfegh A, Jacobson SH, Lundahl J (2013) Leukocyte proliferation and immune modulator production in patients with chronic kidney disease. PLoS ONE 8:e73141

    CAS  PubMed  PubMed Central  Google Scholar 

  94. Scicchitano BM, Rizzuto E, Musarò A (2009) Counteracting muscle wasting in aging and neuromuscular diseases: the critical role of IGF-1. Aging (Albany NY) 1:451–457

    CAS  Google Scholar 

  95. Park SH, Jia T, Qureshi AR, Bárány P, Heimbürger O, Larsson TE, Axelsson J, Stenvinkel P, Lindholm B (2013) Determinants and survival implications of low bone mineral density in end-stage renal disease patients. J Nephrol 26:485–494

    CAS  PubMed  Google Scholar 

  96. Rashid Qureshi A, Alvestrand A, Divino-Filho JC, Gutierrez A, Heimbürger O, Lindholm B, Bergström J (2001) Inflammation, malnutrition, and cardiac disease as predictors of mortality in hemodialysis patients. J Am Soc Nephrol 13:S28-36

    Google Scholar 

  97. Strutz F, Zeisberg M, Hemmerlein B, Sattler B, Hummel K, Becker V, Müller GA (2000) Basic fibroblast growth factor expression is increased in human renal fibrogenesis and may mediate autocrine fibroblast proliferation. Kidney Int 57:1521–1538

    CAS  PubMed  Google Scholar 

  98. Colaianni G, Cuscito C, Mongelli T et al (2015) The myokine irisin increases cortical bone mass. Proc Natl Acad Sci U S A 112:12157–12162

    CAS  PubMed  PubMed Central  Google Scholar 

  99. Shan T, Liang X, Bi P, Kuang S (2013) Myostatin knockout drives browning of white adipose tissue through activating the AMPK-PGC1-Fndc5 pathway in muscle. FASEB J 27:1981–1989

    CAS  PubMed  PubMed Central  Google Scholar 

  100. Wen MS, Wang CY, Lin SL, Hung KC (2013) Decrease in irisin in patients with chronic kidney disease. PLoS ONE 8:e64025

    CAS  PubMed  PubMed Central  Google Scholar 

  101. Ebert T, Focke D, Petroff D et al (2014) Serum levels of the myokine irisin in relation to metabolic and renal function. Eur J Endocrinol 170:501–506

    CAS  PubMed  Google Scholar 

  102. Reginster J-Y, Beaudart C, Buckinx F, Bruyère O (2016) Osteoporosis and sarcopenia: two diseases or one? Curr Opin Clin Nutr Metab Care 19:31–36

    PubMed  Google Scholar 

  103. Yang A, Lv Q, Chen F, Wang Y, Liu Y, Shi W, Liu Y, Wang D (2020) The effect of vitamin D on sarcopenia depends on the level of physical activity in older adults. J Cachexia Sarcopenia Muscle 11:678–689

    PubMed  PubMed Central  Google Scholar 

  104. Wallace TC, Frankenfeld CL (2017) Dietary protein intake above the current RDA and bone health: a systematic review and meta-analysis. J Am Coll Nutr 36:481–496

    CAS  PubMed  Google Scholar 

  105. Verlaan S, Maier AB, Bauer JM et al (2018) Sufficient levels of 25-hydroxyvitamin D and protein intake required to increase muscle mass in sarcopenic older adults – the PROVIDE study. Clin Nutr 37:551–557

    CAS  PubMed  Google Scholar 

  106. Mera P, Laue K, Wei J, Berger JM, Karsenty G (2016) Osteocalcin is necessary and sufficient to maintain muscle mass in older mice. Mol Metab 5:1042–1047

    CAS  PubMed  PubMed Central  Google Scholar 

  107. Oury F, Sumara G, Sumara O et al (2011) Endocrine regulation of male fertility by the skeleton. Cell 144:796–809

    CAS  PubMed  PubMed Central  Google Scholar 

  108. Mera P, Laue K, Ferron M et al (2016) Osteocalcin signaling in myofibers is necessary and sufficient for optimum adaptation to exercise. Cell Metab 23:1078–1092

    CAS  PubMed  PubMed Central  Google Scholar 

  109. Karczewska-Kupczewska M, Stefanowicz M, Matulewicz N, Nikołajuk A, Straczkowski M (2016) Wnt signaling genes in adipose tissue and skeletal muscle of humans with different degrees of insulin sensitivity. J Clin Endocrinol Metab 101:3079–3087

    CAS  PubMed  Google Scholar 

  110. Huang J, Romero-Suarez S, Lara N et al (2017) Crosstalk between MLO-Y4 osteocytes and C2C12 muscle cells is mediated by the Wnt/β-catenin pathway. JBMR Plus 1:86–100

    CAS  PubMed  PubMed Central  Google Scholar 

  111. Kim JA, Roh E, Hong S, hyeon et al (2019) Association of serum sclerostin levels with low skeletal muscle mass: the korean sarcopenic obesity study (KSOS). Bone 128:115053

    CAS  PubMed  Google Scholar 

  112. Zhou D, Fu H, Zhang L, Zhang K, Min Y, Xiao L, Lin L, Bastacky SI, Liu Y (2017) Tubule-derived wnts are required for fibroblast activation and kidney fibrosis. J Am Soc Nephrol 28:2322–2336

    CAS  PubMed  PubMed Central  Google Scholar 

  113. Langen RCJ, Schols AMWJ, Kelders MCJM, Wouters EFM, Janssen-Heininger YMW (2001) Inflammatory cytokines inhibit myogenic differentiation through activation of nuclear factor-κΒ. FASEB J 15:1169–1180

    CAS  PubMed  Google Scholar 

  114. Bonnet N, Bourgoin L, Biver E, Douni E, Ferrari S (2019) RANKL inhibition improves muscle strength and insulin sensitivity and restores bone mass. J Clin Invest 129:3214–3223

    PubMed  PubMed Central  Google Scholar 

  115. Huang JC, Sakata T, Pfleger LL, Bencsik M, Halloran BP, Bikle DD, Nissenson RA (2004) PTH differentially regulates expression of RANKL and OPG. J Bone Miner Res 19:235–244

    CAS  PubMed  Google Scholar 

  116. Russo CR (2009) The effects of exercise on bone. Basic concepts and implications for the prevention of fractures. Clin Cases Miner Bone Metab 6:223–228

    PubMed  Google Scholar 

  117. Alghadir AH, Gabr SA, Al-Eisa ES, Alghadir MH (2016) Correlation between bone mineral density and serum trace elements in response to supervised aerobic training in older adults. Clin Interv Aging 11:265–273

    CAS  PubMed  PubMed Central  Google Scholar 

  118. Marques EA, Mota J, Carvalho J (2012) Exercise effects on bone mineral density in older adults: a meta-analysis of randomized controlled trials. Age (Omaha) 34:1493–1515

    Google Scholar 

  119. Marinho SM, Moraes C, Barbosa DSM, JE, Eduardo JCC, Fouque D, Pelletier S, Mafra D, (2016) Exercise training alters the bone mineral density of hemodialysis patients. J Strength Cond Res 30:2918–2923

    PubMed  Google Scholar 

  120. Adami S, Gatti D, Viapiana O, Fiore CE, Nuti R, Luisetto G, Ponte M, Rossini M (2008) Physical activity and bone turnover markers: a cross-sectional and a longitudinal study. Calcif Tissue Int 83:388–392

    CAS  PubMed  Google Scholar 

  121. Joseph AM, Adhihetty PJ, Leeuwenburgh C (2016) Beneficial effects of exercise on age-related mitochondrial dysfunction and oxidative stress in skeletal muscle. J Physiol 594:5105–5123

    CAS  PubMed  Google Scholar 

  122. Watson EL, Gould DW, Wilkinson TJ, Xenophontos S, Clarke AL, Vogt BP, Viana JL, Smith AC (2018) Twelve-week combined resistance and aerobic training confers greater benefits than aerobic training alone in nondialysis CKD. Am J Physiol Physiol 314:F1188–F1196

    CAS  Google Scholar 

  123. Greenwood SA, Koufaki P, Mercer TH et al (2015) Effect of exercise training on estimated GFR, vascular health, and cardiorespiratory fitness in patients with CKD: a pilot randomized controlled trial. Am J Kidney Dis 65:425–434

    PubMed  Google Scholar 

  124. Howden EJ, Coombes JS, Isbel NM (2015) The role of exercise training in the management of chronic kidney disease. Curr Opin Nephrol Hypertens 24:480–487

    PubMed  Google Scholar 

  125. Harada K, Suzuki S, Ishii H et al (2017) Impact of skeletal muscle mass on long-term adverse cardiovascular outcomes in patients with chronic kidney disease. Am J Cardiol 119:1275–1280

    PubMed  Google Scholar 

  126. Kim YS, Nam JS, Yeo DW, Kim KR, Suh SH, Ahn CW (2015) The effects of aerobic exercise training on serum osteocalcin, adipocytokines and insulin resistance on obese young males. Clin Endocrinol (Oxf) 82:686–694

    CAS  Google Scholar 

  127. Ahn N, Kim K (2016) Effects of 12-week exercise training on osteocalcin, high-sensitivity c-reactive protein concentrations, and insulin resistance in elderly females with osteoporosis. J Phys Ther Sci 28:2227–2231

    PubMed  PubMed Central  Google Scholar 

  128. Lin CF, Huang TH, Tu KC, Lin LL, Tu YH, Sen YR (2012) Acute effects of plyometric jumping and intermittent running on serum bone markers in young males. Eur J Appl Physiol 112:1475–1484

    PubMed  Google Scholar 

  129. Chowdhury S, Schulz L, Palmisano B et al (2020) Muscle-derived interleukin 6 increases exercise capacity by signaling in osteoblasts. J Clin Invest 130:2888–2902

    CAS  PubMed  PubMed Central  Google Scholar 

  130. Cardoso DF, Marques EA, Leal DV, Ferreira A, Baker LA, Smith AC, Viana JL (2020) Impact of physical activity and exercise on bone health in patients with chronic kidney disease: a systematic review of observational and experimental studies. BMC Nephrol 21:1–11

    Google Scholar 

  131. Gomes TS, Aoike DT, Baria F, Graciolli FG, Moyses RMA, Cuppari L (2017) Effect of aerobic exercise on markers of bone metabolism of overweight and obese patients with chronic kidney disease. J Ren Nutr 27:364–371

    CAS  PubMed  Google Scholar 

  132. Liao MT, Liu WC, Lin FH, Huang CF, Chen SY, Liu CC, Lin SH, Lu KC, Wu CC (2016) Intradialytic aerobic cycling exercise alleviates inflammation and improves endothelial progenitor cell count and bone density in hemodialysis patients. Med (United States) 95:e4134

    CAS  Google Scholar 

  133. Marinho SM, Carraro Eduardo JC, Mafra D (2017) Effect of a resistance exercise training program on bone markers in hemodialysis patients. Sci Sports 32:99–105

    Google Scholar 

  134. Marinho SMS A, Mafra D, Pelletier S, Hage V, Teuma C, Laville M, Carraro Eduardo JC, Fouque D (2016) In hemodialysis patients, intradialytic resistance exercise improves osteoblast function: a pilot study. J Ren Nutr 26:341–345

    Google Scholar 

  135. Roghani T, Torkaman G, Movasseghe S, Hedayati M, Goosheh B, Bayat N (2013) Effects of short-term aerobic exercise with and without external loading on bone metabolism and balance in postmenopausal women with osteoporosis. Rheumatol Int 33:291–298

    CAS  PubMed  Google Scholar 

  136. Tobeiha M, Moghadasian MH, Amin N, Jafarnejad S (2020) RANKL/RANK/OPG pathway: a mechanism involved in exercise-induced bone remodeling. Biomed Res Int. https://doi.org/10.1155/2020/6910312

    Article  PubMed  PubMed Central  Google Scholar 

  137. Fiuza-Luces C, Garatachea N, Berger NA, Lucia A (2013) Exercise is the real polypill. Physiology 28:330–358

    CAS  PubMed  Google Scholar 

  138. Scott JPR, Sale C, Greeves JP, Casey A, Dutton J, Fraser WD (2011) The role of exercise intensity in the bone metabolic response to an acute bout of weight-bearing exercise. J Appl Physiol 110:423–432

    CAS  PubMed  Google Scholar 

  139. Bergström I, Parini P, Gustafsson SA, Andersson G, Brinck J (2012) Physical training increases osteoprotegerin in postmenopausal women. J Bone Miner Metab 30:202–207

    PubMed  Google Scholar 

  140. Notomi T, Karasaki I, Okazaki Y, Okimoto N, Kato Y, Ohura K, Noda M, Nakamura T, Suzuki M (2014) Insulinogenic sucrose+amino acid mixture ingestion immediately after resistance exercise has an anabolic effect on bone compared with non-insulinogenic fructose+amino acid mixture in growing rats. Bone 65:42–48

    CAS  PubMed  Google Scholar 

  141. Rubin J, Murphy T, Nanes MS, Fan X (2000) Mechanical strain inhibits expression of osteoclast differentiation factor by murine stromal cells. Am J Physiol - Cell Physiol 278:C1126–C1132

    CAS  PubMed  Google Scholar 

  142. Mezil YA, Allison D, Kish K, Ditor D, Ward WE, Tsiani E, Klentrou P (2015) Response of bone turnover markers and cytokines to high-intensity low-impact exercise. Med Sci Sports Exerc 47:1495–1502

    CAS  PubMed  Google Scholar 

  143. Marques EA, Wanderley F, Machado L, Sousa F, Viana JL, Moreira-Gonçalves D, Moreira P, Mota J, Carvalho J (2011) Effects of resistance and aerobic exercise on physical function, bone mineral density, OPG and RANKL in older women. Exp Gerontol 46:524–532

    CAS  PubMed  Google Scholar 

  144. Johansen KL, Chertow GM, Ng AV, Mulligan K, Carey S, Schoenfeld PY, Kent-Braun JA (2000) Physical activity levels in patients on hemodialysis and healthy sedentary controls. Kidney Int 57:2564–2570

    CAS  PubMed  Google Scholar 

  145. Segura-Ortí E, Gordon P, Doyle J, Johansen KL (2018) Correlates of physical functioning and performance across the spectrum of kidney function. Clin Nurs Res 27:579–596

    PubMed  Google Scholar 

  146. Clark BC (2009) In vivo alterations in skeletal muscle form and function after disuse atrophy. Med Sci Sports Exerc 41:1869–1875

    CAS  PubMed  Google Scholar 

  147. Park H, Park S, Shephard RJ, Aoyagi Y (2010) Yearlong physical activity and sarcopenia in older adults: the nakanojo study. Eur J Appl Physiol 109:953–961

    PubMed  Google Scholar 

  148. Johansen KL, Chertow GM, Da Silva M, Carey S, Painter P (2001) Determinants of physical performance in ambulatory patients on hemodialysis. Kidney Int 60:1586–1591

    CAS  PubMed  Google Scholar 

  149. John SG, Sigrist MK, Taal MW, McIntyre CW (2013) Natural history of skeletal muscle mass changes in chronic kidney disease stage 4 and 5 patients: an observational study. PLoS ONE 8:e65372

    CAS  PubMed  PubMed Central  Google Scholar 

  150. Nielsen AR, Mounier R, Plomgaard P, Mortensen OH, Penkowa M, Speerschneider T, Pilegaard H, Pedersen BK (2007) Expression of interleukin-15 in human skeletal muscle - effect of exercise and muscle fibre type composition. J Physiol 584:305–312

    CAS  PubMed  PubMed Central  Google Scholar 

  151. Pedersen BK, Febbraio MA (2012) Muscles, exercise and obesity: skeletal muscle as a secretory organ. Nat Rev Endocrinol 8:457–465

    CAS  PubMed  Google Scholar 

  152. Huh JY (2018) The role of exercise-induced myokines in regulating metabolism. Arch Pharm Res 41:14–29

    CAS  PubMed  Google Scholar 

  153. Pillon NJ, Bilan PJ, Fink LN, Klip A (2013) Cross-talk between skeletal muscle and immune cells: muscle-derived mediators and metabolic implications. Am J Physiol Metab 304:E453-465

    CAS  Google Scholar 

  154. Kopple JD, Wang H, Casaburi R, Fournier M, Lewis MI, Taylor W, Storer TW (2007) Exercise in maintenance hemodialysis patients induces transcriptional changes in genes favoring anabolic muscle. J Am Soc Nephrol 18:2975–2986

    CAS  PubMed  Google Scholar 

  155. Moore DR, McKay BR, Tarnopolsky MA, Parise G (2018) Blunted satellite cell response is associated with dysregulated IGF-1 expression after exercise with age. Eur J Appl Physiol 118:2225–2231

    CAS  PubMed  Google Scholar 

  156. Liu R, Schindeler A, Little DG (2010) The potential role of muscle in bone repair. J Musculoskelet Neuronal Interact 10:71–76

    CAS  PubMed  Google Scholar 

  157. Macias BR, Swift JM, Nilsson MI, Hogan HA, Bouse SD, Bloomfield SA (2012) Simulated resistance training, but not alendronate, increases cortical bone formation and suppresses sclerostin during disuse. J Appl Physiol 112:918–925

    CAS  PubMed  Google Scholar 

  158. Asamiya Y, Tsuchiya K, Nitta K (2016) Role of sclerostin in the pathogenesis of chronic kidney disease-mineral bone disorder. Ren Replace Ther 2:8

    Google Scholar 

  159. Hamrick MW, McNeil PL, Patterson SL (2010) Role of muscle-derived growth factors in bone formation. J Musculoskelet Neuronal Interact 10:64–70

    CAS  PubMed  Google Scholar 

  160. Clarke MSF, Feerack DL (1996) Mechanical load induces sarcoplasmic wounding and FGF release in differentiated human skeletal muscle cultures. FASEB J 10:502–509

    CAS  PubMed  Google Scholar 

  161. Viana JL, Kosmadakis GC, Watson EL, Bevington A, Feehally J, Bishop NC, Smith AC (2014) Evidence for anti-inflammatory effects of exercise in CKD. J Am Soc Nephrol 25:2121–2130

    PubMed  PubMed Central  Google Scholar 

  162. Shioi A, Katagi M, Okuno Y, Mori K, Jono S, Koyama H, Nishizawa Y (2002) Induction of bone-type alkaline phosphatase in human vascular smooth muscle cells: roles of tumor necrosis factor-α and oncostatin M derived from macrophages. Circ Res 91:9–16

    CAS  PubMed  Google Scholar 

  163. Watson EL, Viana JL, Wimbury D, Martin N, Greening NJ, Barratt J, Smith AC (2017) The effect of resistance exercise on inflammatory and myogenic markers in patients with chronic kidney disease. Front Physiol 8:541

    PubMed  PubMed Central  Google Scholar 

  164. Medina-Gomez C, Kemp JP, Dimou NL et al (2017) Bivariate genome-wide association meta-analysis of pediatric musculoskeletal traits reveals pleiotropic effects at the SREBF1/TOM1L2 locus. Nat Commun 8:1–10

    CAS  Google Scholar 

  165. Wang XH, Du J, Klein JD, Bailey JL, Mitch WE (2009) Exercise ameliorates chronic kidney disease-induced defects in muscle protein metabolism and progenitor cell function. Kidney Int 76:751–759

    CAS  PubMed  Google Scholar 

  166. Louis E, Raue U, Yang Y, Jemiolo B, Trappe S (2007) Time course of proteolytic, cytokine, and myostatin gene expression after acute exercise in human skeletal muscle. J Appl Physiol 103:1744–1751

    CAS  PubMed  Google Scholar 

  167. Baxter-Jones ADG, Kontulainen SA, Faulkner RA, Bailey DA (2008) A longitudinal study of the relationship of physical activity to bone mineral accrual from adolescence to young adulthood. Bone 43:1101–1107

    PubMed  Google Scholar 

  168. Boström P, Wu J, Jedrychowski MP et al (2012) A PGC1-α-dependent myokine that drives brown-fat-like development of white fat and thermogenesis. Nature 481:463–468

    PubMed  PubMed Central  Google Scholar 

  169. Colaianni G, Cuscito C, Mongelli T, Oranger A, Mori G, Brunetti G, Colucci S, Cinti S, Grano M (2014) Irisin enhances osteoblast differentiation in vitro. Int J Endocrinol. https://doi.org/10.1155/2014/902186

    Article  PubMed  PubMed Central  Google Scholar 

  170. Moraes C, Leal VO, Marinho SM, Barroso SG, Rocha GS, Boaventura GT, Mafra D (2013) Resistance exercise training does not affect plasma irisin levels of hemodialysis patients. Horm Metab Res 45:900–904

    CAS  PubMed  Google Scholar 

  171. Zhou Y, Hellberg M, Hellmark T, Höglund P, Clyne N (2019) Muscle mass and plasma myostatin after exercise training: a substudy of renal exercise (RENEXC)—a randomized controlled trial. Nephrol Dial Transplant. https://doi.org/10.1093/ndt/gfz210

    Article  PubMed  PubMed Central  Google Scholar 

  172. Esposito P, La Porta E, Calatroni M et al (2017) Modulation of myostatin/hepatocyte growth factor balance by different hemodialysis modalities. Biomed Res Int 1:1–5

    Google Scholar 

  173. Wang H, Casaburi R, Taylor WE, Aboellail H, Storer TW, Kopple JD (2005) Skeletal muscle mRNA for IGF-IEa, IGF-II, and IGF-I receptor is decreased in sedentary chronic hemodialysis patients. Kidney Int 68:352–361

    CAS  PubMed  Google Scholar 

  174. Han DS, Chen YM, Lin SY, Chang HH, Huang TM, Chi YC, Yang WS (2011) Serum myostatin levels and grip strength in normal subjects and patients on maintenance haemodialysis. Clin Endocrinol (Oxf) 75:857–863

    CAS  Google Scholar 

  175. Wang CJ, Johansen KL (2019) Are dialysis patients too frail to exercise? Semin Dial 32:291–296

    PubMed  Google Scholar 

  176. Watson EL, Major RW, Wilkinson TJ, Greening NJ, Gould DW, Barratt J, Smith AC (2020) The association of muscle size, strength and exercise capacity with all-cause mortality in non-dialysis-dependent CKD patients. Clin Physiol Funct Imaging 40(6):399–406

    PubMed  Google Scholar 

  177. Lombardi G, Ziemann E, Banfi G (2019) Physical activity and bone health: what is the role of immune system? A narrative review of the third way. Front Endocrinol (Lausanne). https://doi.org/10.3389/fendo.2019.00060

    Article  Google Scholar 

  178. Viana JL, Martins P, Parker K et al (2019) Sustained exercise programs for hemodialysis patients: the characteristics of successful approaches in Portugal, Canada, Mexico, and Germany. Semin Dial 32:320–330

    PubMed  Google Scholar 

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Acknowledgements

Research Center in Sports Sciences, Health Sciences and Human Development, CIDESD, is supported by the Portuguese Foundation of Science and Technology (UID/04045/2020).

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Research Center in Sports Sciences, Health Sciences and Human Development, CIDESD, is supported by the Portuguese Foundation of Science and Technology (UID/04045/2020).

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JLV had the idea for the article. DVL drafted versions of the manuscript with input and revisions from JVL, AF, ELW and KRW. All authors contributed to the article and approved the submitted version.

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Leal, D.V., Ferreira, A., Watson, E.L. et al. Muscle-Bone Crosstalk in Chronic Kidney Disease: The Potential Modulatory Effects of Exercise. Calcif Tissue Int 108, 461–475 (2021). https://doi.org/10.1007/s00223-020-00782-4

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