판토프라졸이 난소 적출한 ICR 생쥐의 골교체에 미치는 영향
The Effect of Pantoprazole on Bone Turnover in Ovariectomized ICR Mice
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목적: 장기간의 양성자 펌프 억제제 투여는 골다공증과 연관된 병적 골절과 연관이 있다고 알려져 있다. 그러나 양성자 펌프 억제제의 장기간 사용이 어떤 기전으로 골절의 위험을 높이는지에 대해서는 알려지지 않았다. 이 연구는 난소 적출한 ICR 생쥐의 골교체에 양성자 펌프 억제제인 판토프라졸이 미치는 영향을 알아보고자 하였다. 방법: 실험동물로 난소를 적출한 암컷 ICR 생쥐를 사용하였다. 이들은 무작위로 판토프라졸군(n=10) 및 대조군(n=10)으로 나누었다. 판토프라졸군은 매일 20 mg/kg의 판토프라졸을 복강 내로 두 차례씩 주입했다. 4주간의 실험이 끝난 뒤 이들을 희생시켜 골밀도 및 경골의 건중량을 측정하였고 채취한 혈액으로 ELISA를 이용하여 골교체 표지자인 osteocalcin 및 CTX-1을 측정하였다. 또한, 비장을 추출하여 균질화한 후 RT-PCR을 통해 파골세포의 분화를 촉진하는 사이토카인의 발현을 측정하였다. 골대사와 연관이 있는 혈청 calcium, phosphorus, ALP (alkaline phosphatase) 등도 측정하였다. 결과: 혈청 osteocalcin 농도는 판토프라졸군에서 의미있게 낮게 측정되었으나(p=0.023) 골밀도, 경골의 건중량, 그리고 혈청 ALP, calcium, phosphorus, CTX-1 농도는 양 군 간에 유의한 차이를 보이지 않았다. RT-PCR을 통해 측정한 IL-1β의 발현은 판토프라졸군에서 감소하는 경향을 보였으나(p=0.058), TNF-α, IL-1β, IL-6의 발현은 양 군 간에 유의한 차이를 보이지 않았다. 결론: 이번 실험에서 판토프라졸은 난소를 적출한 ICR 생쥐의 혈청 osteocalcin 농도 및 비장 세포에서의 IL-1β 활성도를 감소시켜 판토프라졸이 골형성 및 골흡수에 영향을 미칠 수 있음을 보여주었다. 그러나 추후 보다 많은 개체수를 이용한 추가적인 연구가 더 필요할 것으로 생각한다.
Abstract
Background/Aims: Long-term exposure to proton pump inhibitors is associated with osteoporosis-related fractures; however, the mechanism is unknown. The purpose of this study was to evaluate the effect of pantoprazole on osteoporosis and bone turnover in ovariectomized ICR mice fed a calcium-free diet. Methods: Ovariectomized female ICR mice were divided into a pantoprazole group (n=10) and a control group (n=10). The mice in the pantoprazole group were given an intraperitoneal injection of pantoprazole at 20 mg/kg twice daily. After 4 weeks, the mice were humanely euthanized, and bone mineral density (BMD) and dry tibia weight were measured. Serum osteocalcin and CTX-1 levels were measured by enzyme-linked immunosorbent assay. The mRNA expression levels of cytokines that stimulate osteoclast differentiation were determined using RT-PCR. Serum calcium, phosphorus, and alkaline phosphatase (ALP) levels were also analyzed. Results: Serum osteocalcin concentration was significantly lower in the pantoprazole group compared with the control group (p=0.023). There was no difference in BMD, dry tibia weight, or serum ALP, calcium, phosphorus, or CTX-1 between the two groups. The expression of interleukin (IL)-1β was lower in the pantoprazole group compared with the control group, but not significantly lower (p=0.058). The levels of tumor necrosis factor-α and IL-6 did not differ between the two groups. Conclusions: Pantoprazole, a proton pump inhibitor, decreased serum osteocalcin and suppressed IL-1β expression, suggesting that pantoprazole affects bone formation and resorption in ovariectomized ICR mice. Further studies using larger sample sizes are needed. (Korean J Med 2011;80:56-62)
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