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Xia Q.,Center for Stem Cells and Tissue Engineering | Xia Q.,Zhejiang Provincial Key Laboratory of Tissue Engineering and Regenerative Medicine | Zhu S.,Center for Stem Cells and Tissue Engineering | Zhu S.,Zhejiang Provincial Key Laboratory of Tissue Engineering and Regenerative Medicine | And 14 more authors.
Stem Cells Translational Medicine | Year: 2015

Osteoarthritis (OA) remainsan intractable clinical challenge. Few drugs are available for reversing this degenerative disease, although some promising candidates have performed well in preclinical studies. Tumor necrosis factor α(TNFα)has been identifiedasacrucial effector modulating OApathogen-esis. This study aimed to investigate the therapeutic effects of Atsttrin, a novel TNFa blocker, on OA treatment. We developed genetically modified mesenchymal stem cells (MSCs) that expressed recombinant Atsttrin (named as MSC-Atsttrin). Expression levels of ADAMTS-5, MMP13, and iNOS of human chondrocytes were analyzed when cocultured with MSC-GFP/Atsttrin. OA animal models were induced byanterior cruciate ligament transection, and MSC-GFP/Atsttrin were injected into the articular cavity 1 week postsurgery. The results showed that MSC-Atsttrin significantly suppressed TNFα-driven up-regulation of matrix proteases and inflammatory factors. Intra-articular injection of MSC-Atsttrin prevented the progression of degenerative changes in the surgically induced OA mouse model. Additionally, levels of detrimental matrix hydrolases were significantly diminished. Compared with nontreated OA samples at 8 weeks postsurgery, the percentages of MMP13- and ADAMTS-5-positive cells were significantly reduced from 91.33% ± 9.87% to 24.33% ± 5.7% (p <.001) and from 91.33% ± 7.1% to 16.67% ± 3.1% (p <.001), respectively. Our results thus indicated that suppression of TNFa activity is an effective strategy for OA treatment and that intra-articular injection of MSCs-Atsttrin could be a promising therapeutic modality. © Alpha Med Press 2015. Source

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