Directed elimination of senescent cells attenuates development of osteoarthritis by inhibition of c-IAP and XIAP

Publication date: Available online 26 June 2019Source: Biochimica et Biophysica Acta (BBA) - Molecular Basis of DiseaseAuthor(s): Wang Peilin, Teng Songsong, Zhuang Chengyu, Cui Zhi, Ma Chunhui, Yu Yinxian, Zhou Lei, Mao Min, Wang Zongyi, Yang Mengkai, Xu Jing, Zhang Tao, Wang Zhuoying, Yin Fei, Yi ChengqingAbstractAging drives the accumulation of senescent cells (SnCs) by secreting factors that cause the senescence-associated secretory phenotype (SASP), including stem cells in the bone marrow, which contribute to aging-related bone degradation. Osteoarthritis (OA) is a serious chronic injury disease, and increasing age is a major risk factor. The accumulation of SnCs may accelerate the development of OA, and the accumulation of SnCs may benefit from its resistance to apoptotic stimuli. Therefore, local elimination of SnCs could be a promising treatment for OA. Apoptosis inhibitor protein (IAP) is an important antiapoptotic protein in vivo. AT-406 is a small molecule inhibitor of the IAP genes and also regulates the transcription of several genes. Here, we show that SnCs upregulate the antiapoptotic proteins c-IAP1, c-IAP2 and XIAP. The combined inhibition of c-IAP1, c-IAP2 and XIAP using siRNA or AT-406 to specific induction of apoptosis SnCs. In addition, XIAP and STX17 bind to each other to regulate the fusion of autophagosomes and lysosomes in SnCs, which in turn, affects the fate of SnCs. It is worth noting that the clearance of SnCs attenuated the secretion of SASP and ...
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - Category: Molecular Biology Source Type: research