The Shraga Segal Department of Microbiology and Immunology, Faculty of Health Sciences, Ben Gurion University of the Negev, Beer Sheva, Israel.
Research Service, Veterans Affairs Health Care Palo Alto, Stanford University, Stanford, CA, USA Medicine Department/Renal Division, Stanford University, Stanford, CA, USA.
Nephrol Dial Transplant. 2016 Aug;31(8):1270-9. doi: 10.1093/ndt/gfv373. Epub 2015 Nov 10.
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.
儿童慢性肾脏病（CKD）与身材矮小和骨矿物质化异常有关。正常的纵向生长取决于骺板（EGP）软骨细胞的适当成熟，从而在初级骨化中心形成小梁骨。我们最近表明，CKD 中的线性生长受损与 EGP 生长激素（GH）受体信号受损有关，运动改善了 CKD 相关肌肉萎缩中的胰岛素样生长因子 I（IGF-I）信号。
在这项研究中，20 天大的大鼠接受 5/6 肾切除术（CKD）或假手术（C），并进行跑步机运动，同时或不补充 GH。
CKD 相关的生长迟缓与 EGP 肥大区增宽有关。运动（胫骨长度除外）并不能完全纠正这种情况。CKD 中的运动改善了 EGP 软骨内骨化的关键因子的表达，如 IGF-I、血管内皮生长因子（VEGF）、核因子 kappa-B 配体受体激活剂（RANKL）和骨钙素。将 GH 治疗与跑步机运动相结合 2 周可改善 CKD 中减少的小梁骨体积，以及生长板 runt 相关转录因子 2、RANKL、金属蛋白酶 13 和 VEGF 的表达，而单独使用 GH 治疗则不能。
跑步机运动可改善胫骨线性生长，以及生长板局部 IGF-I。当与 GH 治疗联合使用时，跑步运动对小梁骨形成具有有益的影响，这表明这种联合治疗对 CKD 相关的身材矮小和骨骼疾病具有潜在的益处。
