Effect of recombinant osteoprotegerin on glucocorticoid-induced osteoporosis in rats / 中国组织工程研究

ABSTRACT

BACKGROUND: Glucocorticoid-induced osteoporosis has relationship with the down-regulation of osteoprotegedn expression. Osteoprotegerin could inhibit bone resorption in the animal experiment and clinical application for treating oestrogenic hormone deficiency osteoporosis. OBJECTIVE: To investigate the effects of exogenous recombinant osteoprotegerin fusion protein on glucocorticoid-induced osteoporosis in rats. DESIGN, TIME AND SETTING: Randomized grouping, controlled animal expenment was performed in the Institute of Orthopedics, Chinese PLA General Hospital between January 2006 and June 2008. MATERIALS Sixty healthy male Wistar rats of clean grade; Dexamethasone was produced by Tianjin Jinyao Amino Acid Co., Ltd (Licenca No. H12020515). METHODS: Sixty rats were divided into 3 groups randomly with 20 rats in each. Control group the rats were administrated with 0.9％ sodium chloride. Dexamethasone group the rats were administrated with dexamethasone intramuscularly. Osteoprotegedn group the rats were administrated with dexamethasone and recombinant osteoprotegerin intramuscularly. MAIN OUTCOME MEASURES: All rats were sacrificed at 12 weeks after administration. The urine calcium, phosphor, creatinine, bone mineral density, biomechanics tests of femur and vertebral body, were measured. Immunohistochemistry staining were performed to observe osteoprotegerin expression.RESULTS: Sixty rats were all involved in the final analysis. ①Compared with control group, udne calcium increased in the Dexamethasone group (P < 0.05); the bone mineral density of lumbar vertebra and femur decreased significantly (P < 0.05), especially lumbar vertebra (P < 0.01); biomechanics tests of femur and vertebral body (maximum load, maximum stress, elasticity load, elasticity stress, elastic modulus) decreased significantly (P < 0.05); immunohistochemistry staining showed that endogenous osteoprotegerin expressions were reduced significantly in bone marrow of Dexamethasone group (P < 0.01). ②Compared with Dexamethasone group, urine calcium decreased in the osteoprotegerin group (P < 0.01 ); the bone mineral density of lumbar vertebra and femur increased (P < 0.05); the parameters of biomechanics testa of femur and vertebral body increased (P < 0.05); the osteoprotegerin expression was not changed between Dexamethasone group and osteoprotegerin group.CONCLUSION: Glucocorticoid could inhibit osteoprotegerin expression in the bone followed by progressive bone loss and induce osteoporosis. Recombinant osteoprotegerin works effectively in inhibiting bone resorption after administrated with glucocorticoid, reduce bone resorption index, increase bone mineral index and bone strength, thus improving the osteoporosis which is induced by glucocorticoid.