Arai Yoshie, Park Sunghyun, Choi Bogyu, Ko Kyoung-Won, Choi Won Chul, Lee Joong-Myung, Han Dong-Wook, Park Hun-Kuk, Han Inbo, Lee Jong Hun, Lee Soo-Hong
Department of Biomedical Science, CHA University, Seongnam-si, Gyeonggi-do 443-742, Korea.
Department of Orthopedic Surgery, Bundang Medical Center, CHA University, Seongnam-si, Gyeonggi-do 443-742, Korea.
Int J Mol Sci. 2016 Jun 17;17(6):963. doi: 10.3390/ijms17060963.
Human adipose-derived stem cells (hASCs) have a capacity to undergo adipogenic, chondrogenic, and osteogenic differentiation. Recently, hASCs were applied to various fields including cell therapy for tissue regeneration. However, it is hard to predict the direction of differentiation of hASCs in real-time. Matrix metalloproteinases (MMPs) are one family of proteolytic enzymes that plays a pivotal role in regulating the biology of stem cells. MMPs secreted by hASCs are expected to show different expression patterns depending on the differentiation state of hASCs because biological functions exhibit different patterns during the differentiation of stem cells. Here, we investigated proteolytic enzyme activity, especially MMP-2 activity, in hASCs during their differentiation. The activities of proteolytic enzymes and MMP-2 were higher during chondrogenic differentiation than during adipogenic and osteogenic differentiation. During chondrogenic differentiation, mRNA expression of MMP-2 and the level of the active form of MMP-2 were increased, which also correlated with Col II. It is concluded that proteolytic enzyme activity and the level of the active form of MMP-2 were increased during chondrogenic differentiation, which was accelerated in the presence of Col II protein. According to our findings, MMP-2 could be a candidate maker for real-time detection of chondrogenic differentiation of hASCs.
人脂肪来源干细胞(hASCs)具有向脂肪细胞、软骨细胞和成骨细胞分化的能力。最近,hASCs已被应用于包括组织再生细胞治疗在内的各个领域。然而,很难实时预测hASCs的分化方向。基质金属蛋白酶(MMPs)是一类蛋白水解酶,在调节干细胞生物学过程中起关键作用。由于干细胞分化过程中生物学功能呈现不同模式,预计hASCs分泌的MMPs会根据hASCs的分化状态表现出不同的表达模式。在此,我们研究了hASCs分化过程中的蛋白水解酶活性,尤其是MMP-2活性。软骨细胞分化过程中蛋白水解酶和MMP-2的活性高于脂肪细胞和成骨细胞分化过程。在软骨细胞分化过程中,MMP-2的mRNA表达和MMP-2活性形式的水平增加,这也与II型胶原蛋白相关。结论是,软骨细胞分化过程中蛋白水解酶活性和MMP-2活性形式的水平增加,在II型胶原蛋白存在时加速。根据我们的研究结果,MMP-2可能是实时检测hASCs软骨细胞分化的候选标志物。