KPNA2 interacts with P65 to modulate catabolic events in osteoarthritis.

Ran Tao, Xinbao Xu, Chi Sun, Youhua Wang, Shitao Wang, Zhongbing Liu, Leilei Zhai, Hongbing Cheng, Min Xiao, Dongmei Zhang

Experimental and molecular pathology 2015 Oct

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Karyopherin alpha 2 (KPNA2) is a member of the importin α family, which acts as an adaptor to deliver P65 to the nucleus by recognizing the classic nuclear localization signal (NLS) of the cargo protein, and which has been reported as being involved in the pathogenesis of many diseases. This study was undertaken to determine the expression and possible functions of KPNA2 in osteoarthritis (OA). KPNA2 expression in cartilage tissues of OA patients and normal controls was detected by RT-PCR and immunohistochemistry. SW1353 cells were stimulated with IL-1β to establish the chondrocyte injury model in vitro. The expression of KPNA2 and catabolic genes in IL-1β-treated SW1353 cells were determined by Western blot. The interaction between KPNA2 and P65 was analyzed by co-immunoprecipitation, the subcellular distribution and transportation of P65 were detected by the subcellular fractionation followed by immunoblot analysis and immunofluorescence. Furthermore, we used RNA interference to analyze the role of KPNA2 in IL-1β-induced P65 nuclear importation and MMP13, ADAMTS-5 expression in SW1353 cells. Cartilage expression of KPNA2 was higher in patients with OA compared with normal controls and mainly locating in chondrocytes. In IL-1β-treated SW1353 cells, up-regulation of KPNA2 was accompanied by the elevated expression of the catabolic marker protein levels, including MMP13 and ADAMTS-5, and increased NF-κB P65 nuclear importation. Knock-down of KPNA2 resulted in decreased catabolic marker protein levels in IL-1β-treated SW1353 cells. KPNA2 interacted with p65, and loss of KPNA2 caused decreased nuclear translocation of the active p50/p65 NF-κB complex. These findings suggested that KPNA2 may promote NF-κB activation via facilitating P65 nuclear transportation, and thus subsequently accelerate the catabolic events of osteoarthritis. Copyright © 2015 Elsevier Inc. All rights reserved.

Citation

Ran Tao, Xinbao Xu, Chi Sun, Youhua Wang, Shitao Wang, Zhongbing Liu, Leilei Zhai, Hongbing Cheng, Min Xiao, Dongmei Zhang. KPNA2 interacts with P65 to modulate catabolic events in osteoarthritis. Experimental and molecular pathology. 2015 Oct;99(2):245-52