Blockage of Osteopontin-Integrin β3 Signaling in Infrapatellar Fat Pad Attenuates Osteoarthritis in Mice

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 (Corresponding Author), To Ngai (Corresponding Author), Ling Qin (Corresponding Author)

Research output: Journal article publicationJournal articleAcademic researchpeer-review

9 Citations (Scopus)

Abstract

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.

Original languageEnglish
Article number2300897
JournalAdvanced Science
Volume10
Issue number22
DOIs
Publication statusPublished - 4 Aug 2023

Keywords

  • infrapatellar fat pad
  • integrin β3
  • nanogel
  • osteoarthritis
  • osteopontin
  • siRNA

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • General Chemical Engineering
  • General Materials Science
  • Biochemistry, Genetics and Molecular Biology (miscellaneous)
  • General Engineering
  • General Physics and Astronomy

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