Blockage of Osteopontin‐Integrin β3 Signaling in Infrapatellar Fat Pad Attenuates Osteoarthritis in Mice
Publication in refereed journal
香港中文大學研究人員
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摘要The knowledge of osteoarthritis (OA) has nowadays been extended from a focalized cartilage disorder to a multifactorial disease. Although recent investigations have reported that infrapatellar fat pad (IPFP) can trigger inflammation in the knee joint, the mechanisms behind the role of IPFP on knee OA progression remain to be defined. Here, dysregulated osteopontin (OPN) and integrin β3 signaling are found in the OA specimens of both human and mice. It is further demonstrated that IPFP-derived OPN participates in OA progression, including activated matrix metallopeptidase 9 in chondrocyte hypertrophy and integrin β3 in IPFP fibrosis. Motivated by these findings, an injectable nanogel is fabricated to provide sustained release of siRNA Cd61 (RGD−Nanogel/siRNA Cd61) that targets integrins. The RGD−Nanogel possesses excellent biocompatibility and desired targeting abilities both in vitro and in vivo. Local injection of RGD−Nanogel/siRNA Cd61 robustly alleviates the cartilage degeneration, suppresses the advancement of tidemark, and reduces the subchondral trabecular bone mass in OA mice. Taken together, this study provides an avenue for developing RGD−Nanogel/siRNA Cd61 therapy to mitigate OA progression via blocking OPN-integrin β3 signaling in IPFP.
出版社接受日期06.05.2023
著者Bingyang Dai, Yuwei Zhu, Xu Li, Zuru Liang, Shunxiang Xu, Shian Zhang, Zhe Zhang, Shanshan Bai, Wenxue Tong, Mingde Cao, Ye Li, Xiaobo Zhu, Wei Liu, Yuantao Zhang, Liang Chang, Patrick Shu-hang Yung, Kevin Ki-wai Ho, Jiankun Xu, To Ngai, Ling Qin
期刊名稱Advanced Science
出版年份2023
月份8
日期4
卷號10
期次22
文章號碼2300897
電子國際標準期刊號2198-3844
語言英式英語
關鍵詞infrapatellar fat pad, integrin β3, nanogel, osteoarthritis, osteopontin, siRNA
