Journal of Life Science (생명과학회지)

Korean Society of Life Science (한국생명과학회)
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Fucoidan Reduces Cellular and Mitochondrial Injury and Improves Impaired Osteogenic Activity in MC3T3-E1 Cells Treated with Advanced Glycation End-products

MC3T3-E1 세포에서 최종당산화물에 의한 세포와 미토콘드리아 손상, 조골세포 분화능, 조골 및 파골 활동성 변화에 미치는 후코이단의 효과

  • Tae Hyun Kim (Department of Physiology, College of Medicine, Pusan National University) ;
  • Jae Suk Woo (Department of Physiology, College of Medicine, Pusan National University)
  • 김태현 (부산대학교 의과대학 생리학교실) ;
  • 우재석 (부산대학교 의과대학 생리학교실)
  • Received : 2024.08.27
  • Accepted : 2024.09.27
  • Published : 2024.10.30
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Abstract

Fucoidan is a polysaccharide found in brown algae, which is known for its various bioactive effects, including immune enhancement, anti-cancer, and anti-inflammatory properties. In this study, the effects of fucoidan on cellular and mitochondrial damage, as well as changes in osteogenic and osteoclastic activities induced by advanced glycation end-products (AGEs) in MC3T3-E1 osteoblast-like cells, were investigated. Treatment with AGEs resulted in a time- and dose-dependent decrease in MTT reduction capacity, activation of caspases (-3, -8, and -9), and an increase in apoptosis. Pre-treatment with fucoidan significantly alleviated these cellular damage markers caused by AGEs. In addition, fucoidan protected against AGEs-induced mitochondrial dysfunction by significantly mitigating the loss of mitochondrial membrane potential, reduction in intracellular ATP levels, and occurrence of mitochondrial permeability transition in AGEs-treated cells. Fucoidan also markedly suppressed the production of reactive oxygen species and, lipid and protein peroxidation induced by AGEs. In cells exposed to AGEs, gene expression related to osteogenic differentiation and markers of osteogenic activity increased, while markers of osteoclastic activity decreased. Fucoidan significantly moderated these changes. In conclusion, AGEs induce mitochondrial dysfunction and apoptosis in MC3T3-E1 cells, while decreasing osteogenic differentiation and activity, and increasing osteoclastic activity. Fucoidan appears to reduce cellular and mitochondrial damage and improve osteogenic activity impaired by AGEs.

후코이단(fucoidan)은 갈조류에서 발견되는 다당류로, 면역 증강, 항암, 항염증 등 다양한 생리 활성을 나타내는 것으로 알려져 있다. 본 연구에서는 조골세포(osteoblast)와 유사한 생물학적 특성을 지닌 MC3T3-E1 세포에서 최종당산화물에 의해 유도되는 세포와 미토콘드리아 손상, 조골세포 분화, 조골 및 파골 활동성의 변화에 미치는 후코이단의 효과를 관찰하였다. 최종당산화물로 처리한 세포군에서는 MTT 환원능의 감소와 함께 카스파아제(caspase)의 활성화, 세포 사멸의 증가가 관찰되었다. 후코이단을 사전 처리하면 최종당산화물에 의한 이들 세포 손상 지표들이 현저히 완화되었다. 후코이단은 또한 최종당산화물에 의해 유도된 미토콘드리아 막 전위 감소, 세포 내 ATP 고갈, 미토콘드리아 막 투과성 전이(mitochondrial permeability transition) 형성을 유의하게 억제하여, 미토콘드리아의 기능적 손상을 완화하는 효과를 보였다. 최종당산화물로 처리한 세포군에서는 반응성 산소종(reactive oxygen species)과 과산화 지질 및 과산화 단백의 생성이 현저히 증가하였으며, 후코이단은 이를 유의하게 억제하였다. 조골세포 분화능의 지표로 뼈형태발생단백-2(bone morphogenetic protein, BMP2), 알칼리 인산분해효소(alkaline phosphatase, ALP), 오스테오칼신 (osteocalcin, OC), 제1형 콜라젠(collagen-I, Col-I)의 mRNA 발현 정도를 정량 실시간 역전사 중합효소 연쇄반응(qRT-PCR) 검사로 분석한 결과 최종당산화물로 처리 시 이들 mRNA들의 발현이 현저히 감소하였으며, 후코이단은 이들 지표 mRNA들의 발현 감소를 유의하게 차단하였다. 조골 활동성(osteogenic activity)의 지표로 알칼리 인산분해효소 활성과 무기질 침착을 측정한 결과도 mRNA 발현의 변화와 일치하는 결과를 보였다. 반면에 파골 활동성(osteoclastic activity)을 나타내는 지표들인 인터루킨-6(interleukin-6)와 NF-kB 리간드 수용체 활성 인자(receptor activator of NF-kB ligand, RANKL)의 분비는 최종당산화물로 처리한 세포군에서 증가하였으며, 후코이단은 이를 유의하게 억제하였다. 이상의 결과를 종합하면 후코이단은 MC3T3-E1 세포에서 최종당산화물에 의해 유도되는 세포 및 미토콘드리아 손상과 조골세포 분화 저해, 조골 활동성 저하를 완화하는 효과를 나타내는 것으로 사료된다.

Keywords

Acknowledgement

이 과제는 부산대학교 기본연구지원사업(2년)에 의하여 연구되었음.

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