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비스포스포네이트가 인간 양수유래 중간엽 줄기세포로부터 조골세포의 분화에 미치는 영향

The effects of bisphosphonates on differentiation of human amniotic fluid-derived mesenchymal stem cells into osteoblast

김상국|주보선|안병민|최태영|문화숙|안준협
대한산부인과학회 (Korean Soceity of Obstetrics and Gynecology)|2009.03|Obstetrics & Gynecology Science|제52권 제3호|pp. 314-321

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참고문헌

키워드

OsteoblastAlendronate조골세포Mesenchymal stem cellZoledronate양수Amniotic fluid중간엽줄기세포
주제분류산부인과학

초록

목적: 최근 양수에서 중간엽줄기세포가 존재함이 알려졌다. 비스포스포네이트는 현재 골다공증의 치료에 가장 많이 사용되는 약제로 파골세포 억제가 일차적인 작용이다. 그러나 비스포스포네이트가 조골세포로의 분화에 미치는 영향이나 작용 기전에 대한 연구는 매우 부족한 실정이다. 특히, zoledronate와 alendronate가 양수유래의 중간엽줄기세포로부터 조골세포로의 분화에 미치는 영향에 대한 연구는 거의 없다. 그러므로 본 연구는 zoledronate와 alendronate가 임신 제2삼분기의 양수세포 유래의 중간엽줄기세포로부터 조골세포로의 분화에 미치는 효과를 조사하고자 한다. 연구 방법: 양수는 6명의 임산부로부터 임신 제2삼분기에 산전 염색체검사를 위한 양수천자에 의해 채취하였다. 채취한 양수유래 중간엽줄기세포에 다양한 농도 (0, 10-10, 10-8, 10-6 M)의 zoledronate와 alendronate를 처리하고 일주일 간격으로 21일째까지 조골세포로의 분화를 각 분화에 특이적인 염색방법과 표지자 발현의 역전사-중합효소반응 (RT-PCR) 방법으로 조사하였다. 조골세포 분화표지자는 alkaline phosphatase (ALP)를 이용하였다. 결과: 양수유래 중간엽줄기세포로부터 조골세포로의 분화가 확인되었다. 조골세포로의 분화능은 zoledronate보다 alendronate에서 보다 강력하였다. Zoledronate는 농도가 증가함에 따라 ALP 발현이 증가한 반면, alendronate는 10-8 M에서 최고치를 보이다가 10-6 M에서 감소하는 경향을 보였다. 그러나 이러한 비스포스포네이트가 ALP 발현에 미치는 효과는 배양 14일째에는 나타나지 않았다. 결론:본 연구는 양수유래 중간엽줄기세포로부터 조골세포로의 분화를 확인할 수 있었으며, 이러한 분화에 zoledronate와 alendronate가 미치는 효과는 비스포스포네이트의 종류, 농도, 시간에 의존적인 양상으로 나타남을 보여주고 있다.

Abstract

Objective: It has been known that amniotic fluid (AF) is rich source of mesenchymal stem cells (MSCs). Bisphosphonates are widely used in clinical treatment of various metabolic bone diseases and their primary action is the inhibition of osteoclastic bone resorption. However, litter is known about whether bisphosphonates affect the differentiation into osteoblast, especially from AF-derived MSCs (AFMSCs). Therefore, the purpose of this study is to investigate whether these bisphosphonates influence in the process of AFMSCs differentiation into osteoblast. Methods: AF samples were obtained by second trimester amniocentesis for fetal karyotyping from 6 pregnant women. Cells were treated with various concentration (0, 10-10, 10-8, 10-6 M) of zoledronate and alendronate and analyzed over 21 days of culture. Differentiation into osteoblast was determined by cell staining and RT-PCR for alkaline phosphatase (ALP). Results: It was observed that AFMSCs could differentiate into osteoblast. Alendronate had more potent effect than zoledronate in osteoblastic differentiation. ALP expression was increased with increasing concentration of zoledronate and it was highest in 10-8 M alendronate. However, no effect of bisphosphonates was found in 14 days of culture. Conclusion: This study shows that AFMSCs can be differentiated into osteoblast. The induction of these differentiation following bisphosphonate treatment was appear to be drug type-, dose-, and culture time-dependent. However, further studies are needed to conclude a consistent outcome for the effects of bisphosphonate on differentiation potential of AFMSCs.

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