期刊
JOURNAL OF CELLULAR BIOCHEMISTRY
卷 120, 期 2, 页码 2198-2212出版社
WILEY
DOI: 10.1002/jcb.27530
关键词
adipose derived mesenchymal stem cell; apoptosis; autophagy; osteoarthritis
资金
- Natural Science Foundation of Guangdong Province [2016A030313217]
- National Natural Science Foundation of China [81102270]
ObjectiveWe aim to explore the effect of adipose derived mesenchymal stem cells (ADMSCs) on a knee osteoarthritis rat model and analyze how ADMSCs affect chondrocyte apoptosis. Materials and MethodsA surgically induced rat knee osteoarthritis (OA) model was constructed. ADMSCs were engrafted into the right knee cavity. Hematoxylin and eosin (H&E), Masson, and Safranin O were used to compare the histopathology of synovial membrane and cartilage. Immunohistochemical (IHC) was used to measure MMP-13, Collagen 2 (Col-2), Caspase-3 (Cas-3), PARP, p62, LC3b, DDR-2, FGFR-1, Wnt, P-AKT/AKT, p-CAMKII/CAMKII, and p-Smad1/Smad1 expression in the articular cartilage. qPCR and Western blot analysis were used to detect mRNA and protein levels of markers in chondrocytes. TUNEL and Annexin-V were used to assess apoptosis. ResultsHistological analysis showed that ADMSCs alleviated the deterioration of cartilage and osteoarthritis. ADMSCs coculture increase the expression of Col2 and Sox-9, while down regulated MMP-13 in IL-1 stimulated chondrocytes. ADMSCs decreased proinflammatory cytokines IL-1, IL-6, and TNF-. ADMSCs enhanced the viability of IL-1 stimulated chondrocytes. ADMSC attenuated chondrocyte apoptosis. The pretreatment of 3-methyladenine (3-MA) reversed the reduction of Caspase-3 caused by ADMSCs, showing that the antiapoptotic effect was associated with autophagy inducing. ADMSCs significantly reduced the expression of FGFR-1, DDR-2, and Wnt in IL-1 stimulated chondrocytes. ADMSCs reduced the ratio of p-Smad1/Smad1 and p-CAMK II/CAMKII, and increased the ratio of p-AKT/AKT. ConclusionsADMSCs treatment alleviate osteoarthritis in rat OA models. AMDSCs reduced the secretion of proinflammatory cytokines and protected against apoptosis through autophagy inducing. ADMSCs' function could be related to multiple signaling pathway.
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