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      KCI등재

      스타틴(statin) 약물이 성체줄기세포의 골분화에 미치는 영향

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      https://www.riss.kr/link?id=A106503209

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      국문 초록 (Abstract)

      골다공증의 진행은 뼈질량 감소와 골절위험 증가를 야기한다. 골다공증은 노인 인구에서 흔하며, 최근 들어 급속한 고령화 사회로 인해 그 환자수도 동반하여 크게 증가하고 있다. 현재 처...

      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 성체 줄기세포의 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.

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      다국어 초록 (Multilingual 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. Mo...

      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.

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      목차 (Table of Contents)

      • 서론
      • 재료 및 방법
      • 결과 및 고찰
      • References
      • 초록
      • 서론
      • 재료 및 방법
      • 결과 및 고찰
      • References
      • 초록
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      참고문헌 (Reference)

      1 Coxon, F. P., "Visualizing mineral binding and uptake of bisphosphonate by osteoclasts and non-resorbing cells" 42 : 848-860, 2008

      2 Campos, R. M., "The role of pro/anti-inflammatory adipokines on bone metabolism in NAFLD obese adolescents : effects of long-term interdisciplinary therapy" 42 : 146-156, 2012

      3 Wong, S. K., "The relationship between metabolic syndrome and osteoporosis : A review" 8 : 347-, 2016

      4 Hwang, D. K., "The relationship between low bone mass and metabolic syndrome in Korean women" 21 : 425-431, 2010

      5 Berebichez-Fridman, R., "The holy grail of orthopedic surgery : mesenchymal stem cells-their current uses and potential applications" 2017 : 2638305-, 2017

      6 Zhou, H., "The effect of atorvastatin, 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor(HMG-CoA), on the prevention of osteoporosis in ovariectomized rabbits" 35 : 245-254, 2017

      7 Mohamed, M. T., "The anti-osteoporotic and anti-atherogenic effects of alendronate and simvastatin in ovariectomized rats fed high fat diet : A comparative study of combination therapy versus monotherapy" 89 : 1115-1124, 2017

      8 Rizzoli, R., "Subtrochanteric fractures after long-term treatment with bisphosphonates : a european society on clinical and economic aspects of osteoporosis and osteoarthritis, and international osteoporosis foundation working group report" 22 : 373-390, 2011

      9 Sobolev, M. S., "Study of endothelio-and osteoprotective effects of combination of rosuvastatin with L-norvaline in experiment" 2018 : 1585749-, 2018

      10 Nakashima, Y., "Stimulation of osteoclast formation by RANKL requires interferon regulatory factor-4and is inhibited by simvastatin in a mouse model of bone loss" 8 : e72033-, 2013

      1 Coxon, F. P., "Visualizing mineral binding and uptake of bisphosphonate by osteoclasts and non-resorbing cells" 42 : 848-860, 2008

      2 Campos, R. M., "The role of pro/anti-inflammatory adipokines on bone metabolism in NAFLD obese adolescents : effects of long-term interdisciplinary therapy" 42 : 146-156, 2012

      3 Wong, S. K., "The relationship between metabolic syndrome and osteoporosis : A review" 8 : 347-, 2016

      4 Hwang, D. K., "The relationship between low bone mass and metabolic syndrome in Korean women" 21 : 425-431, 2010

      5 Berebichez-Fridman, R., "The holy grail of orthopedic surgery : mesenchymal stem cells-their current uses and potential applications" 2017 : 2638305-, 2017

      6 Zhou, H., "The effect of atorvastatin, 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor(HMG-CoA), on the prevention of osteoporosis in ovariectomized rabbits" 35 : 245-254, 2017

      7 Mohamed, M. T., "The anti-osteoporotic and anti-atherogenic effects of alendronate and simvastatin in ovariectomized rats fed high fat diet : A comparative study of combination therapy versus monotherapy" 89 : 1115-1124, 2017

      8 Rizzoli, R., "Subtrochanteric fractures after long-term treatment with bisphosphonates : a european society on clinical and economic aspects of osteoporosis and osteoarthritis, and international osteoporosis foundation working group report" 22 : 373-390, 2011

      9 Sobolev, M. S., "Study of endothelio-and osteoprotective effects of combination of rosuvastatin with L-norvaline in experiment" 2018 : 1585749-, 2018

      10 Nakashima, Y., "Stimulation of osteoclast formation by RANKL requires interferon regulatory factor-4and is inhibited by simvastatin in a mouse model of bone loss" 8 : e72033-, 2013

      11 Mundy, G., "Stimulation of bone formation in vitro and in rodents by statins" 286 : 1946-1949, 1999

      12 Jadhav, S. B., "Statins and osteoporosis : new role for old drugs" 58 : 3-18, 2006

      13 Pagkalos, J., "Simvastatin induces osteogenic differentiation of murine embryonic stem cells" 25 : 2470-2478, 2010

      14 Monjo, M., "Rosuvastatin promotes osteoblast differentiation and regulates SLCO1A1 transporter gene expression in MC3T3-E1 cells" 26 : 647-656, 2010

      15 Qadir, F., "Role of pitavastatin in prevention of osteopenic changes in ovariectomized rats" 26 : 41-45, 2016

      16 Ettinger, B., "Proposed pathogenesis for atypical femoral fractures : lessons from materials research" 55 : 495-500, 2013

      17 Yamaguchi, T., "Plasma lipids and osteoporosis in postmenopausal women" 49 : 211-217, 2002

      18 Ohnaka, K., "Pitavastatin enhanced BMP-2 and osteocalcin expression by inhibition of Rho-associated kinase in human osteoblasts" 287 : 337-342, 2001

      19 Ferretti, C., "Periosteum derived stem cells for regenerative medicine proposals : Boosting current knowledge" 6 : 266-277, 2014

      20 Armas, L. A., "Pathophysiology of osteoporosis : new mechanistic insights" 41 : 475-486, 2012

      21 Reginster, J. Y., "Osteoporosis : a still increasing prevalence" 38 : S4-9, 2006

      22 Khosla, S, "Minireview : the OPG/RANKL/RANK system" 142 : 5050-5055, 2001

      23 Dominici, M., "Minimal criteria for defining multipotent mesenchymal stromal cells, The international society for cellular therapy position statement" 8 : 315-317, 2006

      24 De Bari, C., "Mesenchymal multipotency of adult human periosteal cells demonstrated by single-cell lineage analysis" 54 : 1209-1221, 2006

      25 Ruan, F., "Mechanisms of bone anabolism regulated by statins" 32 : 511-519, 2012

      26 Bu, D. X., "Mechanisms for the anti-inflammatory effects of statins" 22 : 165-170, 2011

      27 Wang, Y. L., "Isolation of mesenchymal stem cells from human alveolar periosteum and effects of vitamin D on osteogenic activity of periosteum-derived cells" 135 : E57166-, 2018

      28 Yang, P. M., "Inhibition of autophagy enhances anticancer effects of atorvastatin in digestive malignancies" 70 : 7699-7709, 2010

      29 Pelton, K., "Hypercholesterolemia promotes an osteoporotic phenotype" 181 : 928-936, 2012

      30 De Bari, C., "Human periosteum-derived cells maintain phenotypic stability and chondrogenic potential throughout expansion regardless of donor age" 44 : 85-95, 2001

      31 Hernandez-Vallejo, S. J., "HIV protease inhibitors induce senescence and alter osteoblastic potential of human bone marrow mesenchymal stem cells : beneficial effect of pravastatin" 12 : 955-965, 2013

      32 Hanayama, R., "Fluvastatin improves osteoporosis in fructose-fed insulin resistant model rats through blockade of the classical mevalonate pathway and antioxidant action" 23 : 581-588, 2009

      33 An, T., "Efficacy of statins for osteoporosis : a systematic review and meta-analysis" 28 : 47-57, 2017

      34 Takayama, T., "Effect of rosuvastatin on coronary atheroma in stable coronary artery disease : multicenter coronary atherosclerosis study measuring effects of rosuvastatin using intravascular ultrasound in Japanese subjects(COSMOS)" 73 : 2110-2117, 2009

      35 Nissen, S. E., "Effect of intensive compared with moderate lipid-lowering therapy on progression of coronary atherosclerosis : a randomized controlled trial" 291 : 1071-1080, 2004

      36 Choudhery, M. S., "Donor age negatively impacts adipose tissue-derived mesenchymal stem cell expansion and differentiation" 12 : 8-, 2014

      37 Yaturu, S., "Decreased bone mineral density in men with metabolic syndrome alone and with type 2 diabetes" 15 : CR5-CR9, 2009

      38 Chung, J. E., "Cultured human periosteum-derived cells can differentiate into osteoblasts in a perioxisome proliferator-activated receptor gamma-mediated fashion via bone morphogenetic protein signaling" 13 : 806-818, 2016

      39 Mendoza, S., "Comparison of the effects of D-003, a mixture of high-molecular-weight aliphatic acids from sugarcane wax, and pravastatin on bones and osteoclast apoptosis of ovariectomized rats" 31 : 181-191, 2005

      40 Shahrezaee, M., "Comparative impact of systemic delivery of atorvastatin, simvastatin, and lovastatin on bone mineral density of the ovariectomized rats" 60 : 138-150, 2018

      41 Tadrous, M., "Comparative gastrointestinal safety of bisphosphonates in primary osteoporosis : a network meta-analysis" 25 : 1225-1235, 2014

      42 Xie, Y., "Bone-targeted delivery of simvastatin-loaded PEG-PLGA micelles conjugated with tetracycline for osteoporosis treatment" 8 : 1090-1102, 2018

      43 Oda, Y., "Bone marrow stromal cells from low-turnover osteoporotic mouse model are less sensitive to the osteogenic effects of fluvastatin" 13 : e0202857-, 2018

      44 Ferreira Junior, D. B., "Biometric, histomorphometric, and biochemical profile in atorvastatin calcium treatment of female rats with dexamethasone-induced osteoporosis" 53 : 607-613, 2018

      45 El-Nabarawi, N., "Atorvastatin, a double weapon in osteoporosis treatment : an experimental and clinical study" 11 : 1383-1391, 2017

      46 Wang, D., "Association between metabolic syndrome and osteoporotic fracture in middle-aged and elderly Chinese peoples" 70 : 1297-1303, 2014

      47 Jain, M. K., "Anti-inflammatory effects of statins : clinical evidence and basic mechanisms" 4 : 977-987, 2005

      48 Pirih, F., "Adverse effects of hyperlipidemia on bone regeneration and strength" 27 : 309-318, 2012

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      학술지 이력
      연월일 이력구분 이력상세 등재구분
      2027 평가예정 재인증평가 신청대상 (재인증)
      2021-01-01 평가 등재학술지 유지 (재인증) KCI등재
      2018-01-01 평가 등재학술지 유지 (등재유지) KCI등재
      2015-01-01 평가 등재학술지 유지 (등재유지) KCI등재
      2011-08-03 학술지명변경 외국어명 : Korean Journal of Life Science -> Journal of Life Science KCI등재
      2011-01-01 평가 등재학술지 유지 (등재유지) KCI등재
      2009-01-01 평가 등재학술지 유지 (등재유지) KCI등재
      2007-01-01 평가 등재학술지 유지 (등재유지) KCI등재
      2004-01-01 평가 등재학술지 선정 (등재후보2차) KCI등재
      2003-01-01 평가 등재후보 1차 PASS (등재후보1차) KCI등재후보
      2001-07-01 평가 등재후보학술지 선정 (신규평가) KCI등재후보
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      기준연도 WOS-KCI 통합IF(2년) KCIF(2년) KCIF(3년)
      2016 0.37 0.37 0.42
      KCIF(4년) KCIF(5년) 중심성지수(3년) 즉시성지수
      0.43 0.43 0.774 0.09
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