Ham Onju, Lee Chang Youn, Song Byeong-Wook, Lee Se-Yeon, Kim Ran, Park Jun-Hee, Lee Jiyun, Seo Hyang-Hee, Lee Chae Yoon, Chung Yong-An, Maeng Lee-So, Lee Min Young, Kim Jongmin, Hwang Jihwan, Woo Dong Kyun, Chang Woochul
Cardiovascular Research Institute, Yonsei University College of Medicine, Seoul 120-752, Korea ; Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul 120-752, Korea.
Mol Cells. 2014 Jun;37(6):449-56. doi: 10.14348/molcells.2014.0023. Epub 2014 Jun 11.
The use of synovial fluid-derived mesenchymal stem cells (SFMSCs) obtained from patients with degenerative arthropathy may serve as an alternative therapeutic strategy in osteoarthritis (OA) and rheumatoid arthritis (RA). For treatment of OA and RA patients, autologous transplantation of differentiated MSCs has several beneficial effects for cartilage regeneration including immunomodulatory activity. In this study, we induced chondrogenic differentiation of SFMSCs by inhibiting protein kinase A (PKA) with a small molecule and microRNA (miRNA). Chondrogenic differentiation was confirmed by PCR and immunocytochemistry using probes specific for aggrecan, the major cartilaginous proteoglycan gene. Absorbance of alcian blue stain to detect chondrogenic differentiation was increased in H-89 and/or miRNA-23btransfected cells. Furthermore, expression of matrix metalloproteinase (MMP)-9 and MMP-2 was decreased in treated cells. Therefore, differentiation of SFMSCs into chondrocytes through inhibition of PKA signaling may be a therapeutic option for OA or RA patients.
从退行性关节病患者获取的滑膜液源性间充质干细胞（SFMSCs）的应用，可能成为骨关节炎（OA）和类风湿关节炎（RA）的一种替代治疗策略。对于OA和RA患者的治疗，分化的间充质干细胞的自体移植对软骨再生具有若干有益作用，包括免疫调节活性。在本研究中，我们通过用小分子和微小RNA（miRNA）抑制蛋白激酶A（PKA）来诱导SFMSCs向软骨细胞分化。使用针对聚集蛋白聚糖（主要的软骨蛋白聚糖基因）的特异性探针，通过PCR和免疫细胞化学证实了软骨细胞分化。在H-89和/或miRNA-23b转染的细胞中，用于检测软骨细胞分化的阿尔新蓝染色的吸光度增加。此外，在处理过的细胞中基质金属蛋白酶（MMP）-9和MMP-2的表达降低。因此，通过抑制PKA信号通路将SFMSCs分化为软骨细胞可能是OA或RA患者的一种治疗选择。
