Abstract
Background and Aims
Hyperphosphatemia and secondary hyperparathyroidism are frequent complications in chronic kidney disease (CKD) which both contribute to increased morbidity and mortality in CKD. Osteogenic factor-1 (OP-1) is an important member of BMPs subfamily and its effects on CKD-associated mineral and bone disorders (MBD) is controversial. The study examined whether exogenous OP-1 administration can modulate disturbed CKD-MBD in adenine-induced chronic uremic rats
Method
Chronic renal failure was induced in adult male SD rats by feeding adenine-containing diet. After adenine diet feeding 3 weeks, animals were injected with OP-1 (5μg/kg/day) intraperitoneally for 2 weeks. The serum and urine phosphorus levels and associated mineral parameters, including fibroblast growth factor 23(FGF-23), DKK-1 and sclerostin were measured. Vascular calcification was assessed by immunohistochemistry staining on aortic tissue. Bony structure was evaluated by microCT (Bruker-microCT, Kontich, Belgium).
Results
A significant decrease of body weight and deteriorated renal function was observed in adenine and OP-1 treatment groups during study period and serum creatinine levels were similar (5.23 ±1.1 mg/dL vs. 5.4 ±1.2 mg/dL, p>0.05). Animals in OP-1 group had lower serum phosphorous (18.7±5.1 vs. 29.0±9.6 mg/dL, p<0.05) and intact parathyroid hormone levels (2906.1±1206.9 vs. 4669.7±2505.9 pg/dL, p<0.05) compared to adenine group. Decreased urine phosphorous excretion was noted in both groups without significant difference. Levels of serum FGF-23, sclerostin and DKK-1 were significantly lower in OP-1 treatment group (all p< 0.05). OP-1 administration diminished the staining of RUNX2 (59.1±3% of adenine-treated group), alkaline-phosphatase (49.4±5.7%), β-caterin (39.3±1.8%), BMP2 (43.2%±6.7%), and BMP7 (51.9±10%, all p <0.05). MicroCT revealed that bone mineral density was increased by OP-1 treatment (0.46±0.1 vs.0.39±0.06 g/cm3). Total volume was increased but bone volume was not changed. OP-1 administration did not affect trabecular thickness and trabecular number.
Conclusion
Our data indicated administration of exogenous OP-1 improved hyperparathyroidism and attenuated vascular calcification. OP-1 treatment was also associated with beneficial effects on bony structure in animals with renal failure.