1,25OH2D3 Alters Growth Plate Maturation and Bone Architecture in Young Rats with Normal Renal FunctionReportar como inadecuado




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Whereas detrimental effects of vitamin D deficiency are known over century, the effects of vitamin D receptor activation by 1,25OH2D3, the principal hormonal form of vitamin D, on the growing bone and its growth plate are less clear. Currently, 1,25OH2D3 is used in pediatric patients with chronic kidney disease and mineral and bone disorder CKD-MBD and is strongly associated with growth retardation. Here, we investigate the effect of 1,25OH2D3 treatment on bone development in normal young rats, unrelated to renal insufficiency. Young rats received daily i.p. injections of 1 µg-kg 1,25OH2D3 for one week, or intermittent 3 µg-kg 1,25OH2D3 for one month. Histological analysis revealed narrower tibial growth plates, predominantly in the hypertrophic zone of 1,25OH2D3-treated animals in both experimental protocols. This phenotype was supported by narrower distribution of aggrecan, collagens II and X mRNA, shown by in situ hybridization. Concomitant with altered chondrocyte maturation, 1,25OH2D3 increased chondrocyte proliferation and apoptosis in terminal hypertrophic cells. In vitro treatment of the chondrocytic cell line ATDC5 with 1,25OH2D3 lowered differentiation and increased proliferation dose and time-dependently. Micro-CT analysis of femurs from 1-week 1,25OH2D3-treated group revealed reduced cortical thickness, elevated cortical porosity, and higher trabecular number and thickness. 1-month administration resulted in a similar cortical phenotype but without effect on trabecular bone. Evaluation of fluorochrome binding with confocal microscopy revealed inhibiting effects of 1,25OH2D3 on intracortical bone formation. This study shows negative effects of 1,25OH2D3 on growth plate and bone which may contribute to the exacerbation of MBD in the CKD pediatric patients.



Autor: Anna Idelevich, Michael Kerschnitzki, Ron Shahar, Efrat Monsonego-Ornan

Fuente: http://plos.srce.hr/



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