title: Endurance exercise and growth hormone improve bone formation in young and growth-retarded chronic kidney disease rats.
abstract: Childhood chronic kidney disease (CKD) is associated with both short stature and abnormal bone mineralization. Normal longitudinal growth depends on proper maturation of epiphyseal growth plate (EGP) chondrocytes, leading to the formation of trabecular bone in the primary ossification centre. We have recently shown that linear growth impairment in CKD is associated with impaired EGP growth hormone (GH) receptor signalling and that exercise improved insulin-like growth factor I (IGF-I) signalling in CKD-related muscle atrophy.
  
  
  
  In this study, 20-day-old rats underwent 5/6 nephrectomy (CKD) or sham surgery (C) and were exercised with treadmill, with or without GH supplementation.
  
  
  
  CKD-related growth retardation was associated with a widened EGP hypertrophic zone. This was not fully corrected by exercise (except for tibial length). Exercise in CKD improved the expression of EGP key factors of endochondral ossification such as IGF-I, vascular endothelial growth factor (VEGF), receptor activator of nuclear factor kappa-B ligand (RANKL) and osteocalcin. Combining GH treatment with treadmill exercise for 2 weeks improved the decreased trabecular bone volume in CKD, as well as the expression of growth plate runt-related transcription factor 2, RANKL, metalloproteinase 13 and VEGF, while GH treatment alone could not do that.
  
  
  
  Treadmill exercise improves tibial bone linear growth, as well as growth plate local IGF-I. When combined with GH treatment, running exercise shows beneficial effects on trabecular bone formation, suggesting the potential benefit of this combination for CKD-related short stature and bone disease.
authors.affiliation: The Shraga Segal Department of Microbiology and Immunology, Faculty of Health Sciences, Ben Gurion University of the Negev, Beer Sheva, Israel.
authors.forename: Ariel
authors.initials: A
authors.lastname: Troib
authors.affiliation: The Shraga Segal Department of Microbiology and Immunology, Faculty of Health Sciences, Ben Gurion University of the Negev, Beer Sheva, Israel.
authors.forename: Mayan
authors.initials: M
authors.lastname: Guterman
authors.affiliation: Research Service, Veterans Affairs Health Care Palo Alto, Stanford University, Stanford, CA, USA Medicine Department/Renal Division, Stanford University, Stanford, CA, USA.
authors.forename: Ralph
authors.initials: R
authors.lastname: Rabkin
authors.affiliation: The Shraga Segal Department of Microbiology and Immunology, Faculty of Health Sciences, Ben Gurion University of the Negev, Beer Sheva, Israel Department of Pediatrics, Schneider Children's Medical Center of Israel, Petach Tikva, Israel.
authors.forename: Daniel
authors.initials: D
authors.lastname: Landau
authors.affiliation: The Shraga Segal Department of Microbiology and Immunology, Faculty of Health Sciences, Ben Gurion University of the Negev, Beer Sheva, Israel.
authors.forename: Yael
authors.initials: Y
authors.lastname: Segev
mesh_terms: D000818:Animals; D001842:Bone and Bones / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D019902:Chondrocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D003131:Combined Modality Therapy; D006130:Growth Disorders / Q000503:physiopathology / Q000628:therapy*; D013006:Growth Hormone / Q000008:administration & dosage*; D008297:Male; D010012:Osteogenesis / Q000187:drug effects* / Q000502:physiology; D010805:Physical Conditioning, Animal; D051381:Rats; D017207:Rats, Sprague-Dawley; D051436:Renal Insufficiency, Chronic / Q000503:physiopathology / Q000628:therapy*
chemical_list: D013006:Growth Hormone
keywords: chronic kidney disease; endochondral ossification; endurance exercise; growth hormone treatment; growth retardation