The Korean Journal of Medicine

The Korean Association of Internal Medicine (대한내과학회)
권호 표지

The Effect of Pantoprazole on Bone Turnover in Ovariectomized ICR Mice

판토프라졸이 난소 적출한 ICR 생쥐의 골교체에 미치는 영향

  • Lim, Eun-Hye (Department of Internal Medicine, Korea University College of Medicine) ;
  • Kim, Key-Hyeon (Department of Internal Medicine, Korea University College of Medicine) ;
  • Lee, Beom-Jae (Department of Internal Medicine, Korea University College of Medicine) ;
  • Joo, Moon-Kyung (Department of Internal Medicine, Korea University College of Medicine) ;
  • Koh, Jin-Sung (Department of Internal Medicine, Korea University College of Medicine) ;
  • Lee, Joon-Young (Department of Internal Medicine, Korea University College of Medicine) ;
  • Lim, Sang-Ah (Department of Internal Medicine, Korea University College of Medicine) ;
  • Kim, Ji-Hoon (Department of Internal Medicine, Korea University College of Medicine) ;
  • Yeon, Jong-Eun (Department of Internal Medicine, Korea University College of Medicine) ;
  • Park, Jong-Jae (Department of Internal Medicine, Korea University College of Medicine) ;
  • Kim, Jae-Seon (Department of Internal Medicine, Korea University College of Medicine) ;
  • Byun, Kwan-Soo (Department of Internal Medicine, Korea University College of Medicine) ;
  • Bak, Young-Tae (Department of Internal Medicine, Korea University College of Medicine)
  • 임은혜 (고려대학교 의과대학 내과학교실) ;
  • 김기현 (고려대학교 의과대학 내과학교실) ;
  • 이범재 (고려대학교 의과대학 내과학교실) ;
  • 주문경 (고려대학교 의과대학 내과학교실) ;
  • 고진성 (고려대학교 의과대학 내과학교실) ;
  • 이준영 (고려대학교 의과대학 내과학교실) ;
  • 임상아 (고려대학교 의과대학 내과학교실) ;
  • 김지훈 (고려대학교 의과대학 내과학교실) ;
  • 연종은 (고려대학교 의과대학 내과학교실) ;
  • 박종재 (고려대학교 의과대학 내과학교실) ;
  • 김재선 (고려대학교 의과대학 내과학교실) ;
  • 변관수 (고려대학교 의과대학 내과학교실) ;
  • 박영태 (고려대학교 의과대학 내과학교실)
  • Published : 2011.01.01
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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 $(IL)-1{\beta}$ was lower in the pantoprazole group compared with the control group, but not significantly lower (p=0.058). The levels of tumor necrosis $factor-{\alpha}$ and IL-6 did not differ between the two groups. Conclusions: Pantoprazole, a proton pump inhibitor, decreased serum osteocalcin and suppressed $IL-1{\beta}$ expression, suggesting that pantoprazole affects bone formation and resorption in ovariectomized ICR mice. Further studies using larger sample sizes are needed.

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 끝난뒤 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 $IL-1{\beta}$의 발현은 판토프라졸군에서 감소하는 경향을 보였으나(p=0.058), $TNF-{\alpha}$, $IL-1{\beta}$, IL-6의 발현은 양 군 간에 유의한 차이를 보이지 않았다. 결론: 이번 실험에서 판토프라졸은 난소를 적출한 ICR 생쥐의 혈청 osteocalcin 농도 및 비장 세포에서의 $IL-1{\beta}$ 활성도를 감소시켜 판토프라졸이 골형성 및 골흡수에 영향을 미칠 수 있음을 보여주었다. 그러나 추후 보다 많은 개체수를 이용한 추가적인 연구가 더 필요할 것으로 생각한다.

Keywords

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