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논문 기본 정보

자료유형
학술저널
저자정보
Abu-Shahba Ahmed G. (University of Helsinki and Helsinki University Hospital) Gebraad Arjen (University of Helsinki and Helsinki University Hospital) Kaur Sippy (University of Helsinki and Helsinki University Hospital) Paananen Riku O. (University of Helsinki and Helsinki University Hospital) Peltoniemi Hilkka (Laser Tilkka Ltd) Seppänen-Kaijansinkko Riitta (University of Helsinki and Helsinki University Hospital) Mannerström Bettina (University of Helsinki and Helsinki University Hospital)
저널정보
한국조직공학과 재생의학회 조직공학과 재생의학 조직공학과 재생의학 제17권 제4호
발행연도
2020.1
수록면
477 - 493 (17page)

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BACKGROUND: Insufficient vascularization hampers bone tissue engineering strategies for reconstructing large bone defects. Delivery of prolyl-hydroxylase inhibitors (PHIs) is an interesting approach to upregulate vascular endothelial growth factor (VEGF) by mimicking hypoxic stabilization of hypoxia-inducible factor-1alpha (HIF-1α). This study assessed two PHIs: dimethyloxalylglycine (DMOG) and baicalein for their effects on human adipose tissue-derived mesenchymal stem/stromal cells (AT-MSCs). METHODS: Isolated AT-MSCs were characterized and treated with PHIs to assess the cellular proliferation response. Immunostaining and western-blots served to verify the HIF-1α stabilization response. The optimized concentrations for long-term treatment were tested for their effects on the cell cycle, apoptosis, cytokine secretion, and osteogenic differentiation of AT-MSCs. Gene expression levels were evaluated for alkaline phosphatase (ALPL), bone morphogenetic protein 2 (BMP2), runt-related transcription factor 2 (RUNX2), vascular endothelial growth factor A (VEGFA), secreted phosphoprotein 1 (SPP1), and collagen type I alpha 1 (COL1A1). In addition, stemness-related genes Kruppel-like factor 4 (KLF4), Nanog homeobox (NANOG), and octamer-binding transcription factor 4 (OCT4) were assessed. RESULTS: PHIs stabilized HIF-1α in a dose-dependent manner and showed evident dose- and time dependent antiproliferative effects. With doses maintaining proliferation, DMOG and baicalein diminished the effect of osteogenic induction on the expression of RUNX2, ALPL, and COL1A1, and suppressed the formation of mineralized matrix. Suppressed osteogenic response of AT-MSCs was accompanied by an upregulation of stemness-related genes. CONCLUSION: PHIs significantly reduced the osteogenic differentiation of AT-MSCs and rather upregulated stemness-related genes. PHIs proangiogenic potential should be weighed against their longterm direct inhibitory effects on the osteogenic differentiation of AT-MSCs.
#Dimethyloxalylglycine Baicalein Hypoxia-inducible factor-1alpha Adipose tissue-derived mesenchymal stem/stromal cells Osteogenesis

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참고문헌 (52)

참고문헌 신청
Kim TG / 2012 / Biomimetic scaffolds for tissue engineering / Adv Funct Mater 22:2446~2468 google schola Koyama N / 2011 / Experimental study of osteoinduction using a new material as a carrier for bone morphogenetic protein-2 / Br J Oral Maxillofac Surg 49:314~318 google schola Szpalski C / 2012 / Bone tissue engineering : current strategies and techniques–part I : scaffolds / Tissue Eng Part B Rev 18:246~257 google schola Wang L / 2014 / Ectopic osteoid and bone formation by three calcium-phosphate ceramics in rats, rabbits and dogs / PLoS One 9:e107044 google schola Zhao X / 2018 / Identification of key genes and pathways associated with osteogenic differentiation of adipose stem cells / J Cell Physiol 233:9777~9785 google schola

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