Blockage of Osteopontin‐Integrin β3 Signaling in Infrapatellar Fat Pad Attenuates Osteoarthritis in Mice
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AbstractThe 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.
Acceptance Date06/05/2023
All Author(s) ListBingyang 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
Journal nameAdvanced Science
Year2023
Month8
Day4
Volume Number10
Issue Number22
Article number2300897
eISSN2198-3844
LanguagesEnglish-United Kingdom
Keywordsinfrapatellar fat pad, integrin β3, nanogel, osteoarthritis, osteopontin, siRNA
