Inhibition of vascular endothelial growth factor with shRNA in chondrocytes ameliorates osteoarthritis

Zhang, Xufang, Crawford, Ross, & Xiao, Yin (2016) Inhibition of vascular endothelial growth factor with shRNA in chondrocytes ameliorates osteoarthritis. Journal of Molecular Medicine, 94(7), pp. 787-798.

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Osteoarthritis (OA) is a chronic, incurable and destructive joint disease that is characterized by chondrocyte hypertrophy and cartilage degradation. Angiogenesis, mediated by the action of vascular endothelial growth factor (VEGF), is known to be a contributing factor in the pathogenesis of OA. In this study, we use a lentivirus-based approach to investigate whether VEGF knockdown would be beneficial to chondrogenesis and could prevent or slow down OA progression. We first profiled cytokines in human OA cartilage using cytokine antibody arrays. This revealed that as many as 21 angiogenesis-related cytokines were significantly upregulated in severe OA cartilage compared to mild OA samples. Next, we infected chondrocytes with VEGF small hairpin RNA (shRNA) lentivirus (LV-VEGF shRNA) and treated these cells with tumour necrosis factor alpha (TNF-α) to induce hypertrophy. The results showed that inhibition of VEGF not only enhanced chondrogenic differentiation, but also protected chondrocytes from TNF-α-induced hypertrophy. We also found that knockdown of VEGF suppressed TNF-α-induced phosphorylation of ERK1/2 in chondrocytes. Furthermore, using a surgically induced OA rat model, we showed that VEGF inhibition delayed OA progression in animals given intra-articular injection of LV-VEGF shRNA. In conclusion, in this study, we have shown that VEGF knockdown can enhance chondrogenesis and prevent OA progression, thus providing evidence that inhibition of VEGF may be a potential therapeutic approach for OA patients.

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ID Code: 95163
Item Type: Journal Article
Refereed: Yes
Keywords: Angiogenesis, Osteoarthritis, Chondrocyte hypertrophy, Vascular endothelial growthfactor, Lentivirus
DOI: 10.1007/s00109-016-1425-0
ISSN: 1432-1440
Subjects: Australian and New Zealand Standard Research Classification > BIOLOGICAL SCIENCES (060000)
Divisions: Current > Institutes > Institute of Health and Biomedical Innovation
Copyright Owner: Copyright 2016 Springer
Deposited On: 29 Jun 2016 00:06
Last Modified: 07 Jul 2016 23:05

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