Journal of Life Science (생명과학회지)

Korean Society of Life Science (한국생명과학회)
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An Analysis for Effects of Stain Family Drugs on Osteogenic Differentiation using Human Periosteum-derived Mesenchymal Stem Cells

스타틴(statin) 약물이 성체줄기세포의 골분화에 미치는 영향

  • Moon, Dong Kyu (Department of Orthopedic Surgery and Institute of Health Sciences, School of Medicine and Hospital, Gyeongsang National University) ;
  • Yun, Jeong-Won (Department of Oral and Maxillofacial Surgery and Institute of Health Sciences, School of Medicine and Hospital, Gyeongsang National University) ;
  • Kim, Bo Gyu (College of Pharmacy and Research Institute of Pharmaceutical Sciences, Gyeongsang National University) ;
  • Lee, A Ram (College of Pharmacy and Research Institute of Pharmaceutical Sciences, Gyeongsang National University) ;
  • Moon, Sun Young (College of Pharmacy and Research Institute of Pharmaceutical Sciences, Gyeongsang National University) ;
  • Byun, June-Ho (Department of Oral and Maxillofacial Surgery and Institute of Health Sciences, School of Medicine and Hospital, Gyeongsang National University) ;
  • Hwang, Sun-Chul (Department of Orthopedic Surgery and Institute of Health Sciences, School of Medicine and Hospital, Gyeongsang National University) ;
  • Woo, Dong Kyun (College of Pharmacy and Research Institute of Pharmaceutical Sciences, Gyeongsang National University)
  • 문동규 (경상대학교병원 정형외과) ;
  • 윤정원 (경상대학교병원 구강악안면외과) ;
  • 김보규 (경상대학교 약학과) ;
  • 이아람 (경상대학교 약학과) ;
  • 문선영 (경상대학교 약학과) ;
  • 변준호 (경상대학교병원 구강악안면외과) ;
  • 황선철 (경상대학교병원 정형외과) ;
  • 우동균 (경상대학교 약학과)
  • Received : 2019.08.28
  • Accepted : 2019.11.19
  • Published : 2019.12.30
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Abstract

Osteoporosis is characterized by a reduction in bone mass and typically manifests as an increase in fractures. Because this disease is common in elderly populations and lifespans are rapidly increasing, the incidence of osteoporosis has also grown. Most drugs currently used for osteoporosis treatment target osteoclasts in the bone tissue to prevent absorption. However, these medications also cause certain side effects and, furthermore, cannot increase bone mass. Thus, in order to control osteoporosis, regenerative medicine that utilizes adult stem cells and osteoblasts has been extensively studied. Statins, also known as 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors, are cholesterol-lowering drugs that have been widely prescribed for cardiovascular diseases. Interestingly, recent studies have reported the beneficial effects of various statins on bone formation via the activation of osteoblasts. Thus, the current study investigated the effects of seven statin-family drugs on osteoblast activity during osteogenic differentiation using adult stem cells from human periosteal tissue. Specifically, statin effects on alkaline phosphatase activity, an early marker of bone cell differentiation, and on calcium deposit, a late marker of bone cell differentiation, were assessed. The results demonstrate that some statins (for example, pitavastatin and pravastatin) have a weak but positive effect on bone formation, and the findings therefore suggest that statin treatments can be a novel modulator for osteogenic differentiation and regenerative medicine using periosteal stem cells.

골다공증의 진행은 뼈질량 감소와 골절위험 증가를 야기한다. 골다공증은 노인 인구에서 흔하며, 최근 들어 급속한 고령화 사회로 인해 그 환자수도 동반하여 크게 증가하고 있다. 현재 처방되는 골다공증 치료제의 대부분은 파골세포 억제 효과에 기반하여 골흡수를 방지한다. 그러나 이러한 골다공증 치료제는 새로운 뼈형성을 증가시키지는 못하며 수반되는 여러 부작용도 보고되고 있다. 따라서 골다공증의 새로운 제어와 치료법 개발을 위해 성체줄기세포의 골세포 분화유도와 조골세포 활성을 도모하는 재생의학적 접근이 활발히 연구되고 있다. 스타틴(statin) 계열 약물은 혈중 콜레스테롤 강하제로 심혈관 질환에 흔히 처방되는 치료제이다. 흥미롭게도 최근 일련의 연구에서 이러한 스타틴이 조골세포 활성에 긍정적인 영향을 주어 뼈형성을 촉진한다는 보고가 발표되고 있다. 따라서, 본 연구에서는 이러한 스타틴 약물이 인체 골막유래 성체줄기세포의 골세포 분화과정이나 조골세포 활성에 영향이 있는 지를 분석하였다. 현재 임상적으로 처방되는 총 7 종류의 스타틴 약물에 대해, 골막유래 성체줄기세포의 골세포 분화과정에서 조골세포 활성과 관련된 초기와 후기 표지자인 alkaline phosphatase의 활성과 칼슘 침착을 각각 분석하였다. 본 연구에서 일부 스타틴(pitavastatin과 pravastatin)은 약하지만 뼈형성을 증가시키는 효과가 있음을 알 수 있었다. 이러한 연구결과는 스타틴이 골막유래 줄기세포로부터 골세포로의 분화나 조골세포 활성을 조절할 수 있는 물질이 될 수 있으며, 이러한 약물이 골세포분화나 재생의학의 새로운 조절 물질로서 골다공증 치료에 응용될 수 있음을 제시한다.

Keywords

References

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