engleski

Systemic effects of bone morphogenetic protein (BMP) 2, BMP6, and BMP7 on bone markers in rats without calciotropic hormones

Bone morphogenetic proteins have been shown in clinical studies to be benefitial in the treatment of a variety of bone-related conditions including delayed non-unions, fractures and spinal fusions. However, their exact effect on bone formation and resorption remained unknown. Therefore, we established a rat model with low serum levels of calciotropic hormones including PTH, 1, 25-(OH)2D3, calcitonin and thyroid hormone. In six months old male Spraque-Dawley rats their thyroid and parathyroid glands were removed (thyroparathyroidectomy-TPTx) and the therapy was initiated by daily administration for 2 weeks for BMP2, BMP6 and BMP7 in different doses as follows: sham, TPTx+vehicle, TPTx+BMP, 10ug/kg, TPTx+BMP, 70ug/kg, TPTx+BMP, 250ug/kg. TPTx surgery resulted in hypocalcemia and hyperphosphataemia, as well as a decreased bone turnover markers in comparison to sham rats. BMP2 therapy in all doses significantly increased the calcium and decreased the phosphate level. The highest dose was the most effective. BMP6 and BMP7 showed no effect on calcium and phosphate level, suggesting their lower bone resorption potency. Osteocalcin and C-telopeptide lvels were also decreased after TPTx. BMP7 more effective influenced bone turnover markers and raised osteocalcin level after only 24 hours, remaining high to the end of experiment. C-telopeptide was increased, and on 7th day of therapy its level was significantly higher then in both the sham and control group. BMP2 increased the serum C-telopeptide at tested doses, and had no effect on the osteocalcin level. Following surgery both RANKL and OPG decreased. BMPs significantly decreased the serum RANKL level when administered at low doses. There was no effect on the serum osteoprotegerin values. We conclude that BMP2 is more active in promoting bone resorption then BMP6 and BMP7.

BMP2; BMP7; osteocalcin; C-telopeptide

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