文献类型：期刊文献

英文题名：Tricalcium phosphate particles promote pyroptotic death of calvaria osteocytes through the ROS/NLRP3/Caspase-1 signaling axis in amouse osteolysis model

作者：Zhang, Yun[1];Yan, Ming[2];Niu, Wanting[3];Mao, Hongjiao[1];Yang, Pei[1];Xu, Bingbing[1];Sun, Yonghong[4]

机构：[1]Shaoxing Univ, Coll Med, Huancheng West Rd 508, Shaoxing 312000, Peoples R China;[2]HangZhou Dianzi Univ, Sch Automat, 1158 2nd Ave, Hangzhou 310018, Peoples R China;[3]Harvard Med Sch, Brigham & Womens Hosp, Dept Orthoped, Boston, MA 02115 USA;[4]Zhejiang Univ, Zhejiang Prov Key Lab Cardiocerebral Vasc Detect, Zheda Rd 38, Hangzhou 310000, Peoples R China

年份：2022

卷号：107

外文期刊名：INTERNATIONAL IMMUNOPHARMACOLOGY

收录：SCI-EXPANDED(收录号：WOS:000793198400001)、、Scopus(收录号：2-s2.0-85126430992)、WOS

基金：Acknowledgments This work was supported by Natural Science Foundation of Zhejiang Province (LY21H060001) and National Natural Science Foundation of China (30900301, 81700936) .

语种：英文

外文关键词：TCP particles; Osteolysis; Osteocytes; Pyroptosis; NLRP3; ROS

外文摘要：Wear particles-induced inflammatory osteolysis, a major factor of aseptic loosening affects the long-term survival of orthopedic prostheses. Increasing observations have demonstrated that osteocytes, making up over 95% of all the bone cells, is involved in wear particle-induced periprosthetic osteolysis, but its mechanism remains unclear. In the present study, we embedded micro-sized tricalcium phosphate (TCP) particles (30 mg) under the peri-osteum around the middle suture of the mouse calvaria to establish a calvarial osteolysis model and investigated the biological effects of the particles on calvaria osteocytes in vivo. Results showed that TCP particles induced pyroptosis and activated the NLRP3 inflammasome in calvaria osteocytes, which was confirmed by obvious increases in empty lacunae, protein expressions of speck-like protein containing CARD (ASC), NOD-like receptor protein 3 (NLRP3), cleaved caspase-1 (Casp-1 p20) and cleaved gasdermin D (GSDMD-N), and resulted in elevated ratios of Casp-1 p20/Casp-1 and interleukin (IL)-1 beta/pro-IL-1 beta. Simultaneously, TCP particles enhanced serum levels of lactate dehydrogenase (LDH) and IL-1 beta. Furthermore, the pyroptotic effect was reversed by the Casp-1 inhibitor VX765 or the NLRP3 inhibitor MCC950. In addition, TCP particles increased the levels of intracellular reactive oxygen species (ROS) and malonaldehyde (MDA), whereas decreased the antioxidant enzyme nuclear factor E2-related factor 2 (Nrf2) level, leading to oxidative stress in calvaria osteocytes; the ROS scavenger N-acetylcysteine (NAC) attenuated these effects of pyroptotic death and the NLPR3 activation trig-gered by TCP particles. Collectively, our data suggested that TCP particles promote pyroptotic death of calvaria osteocytes through the ROS/NLRP3/Caspase-1 signaling axis, contributing to osteoclastogenesis and peri-prosthetic osteolysis.