Dataset Information

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

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.

SUBMITTER: Dai B

PROVIDER: S-EPMC10401113 | biostudies-literature | 2023 Aug

REPOSITORIES: biostudies-literature

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

Dai Bingyang B Zhu Yuwei Y Li Xu X Liang Zuru Z Xu Shunxiang S Zhang Shian S Zhang Zhe Z Bai Shanshan S Tong Wenxue W Cao Mingde M Li Ye Y Zhu Xiaobo X Liu Wei W Zhang Yuantao Y Chang Liang L Yung Patrick Shu-Hang PS Ki-Wai Ho Kevin K Xu Jiankun J Ngai To T Qin Ling L

Advanced science (Weinheim, Baden-Wurttemberg, Germany) 20230523 22

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 OP ...[more]

PMID: 37218542

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Project description:Background Infrapatellar fat pad (IPFP) quality has been implicated as a marker for predicting knee osteoarthritis (KOA); however, no valid quantification for subtle IPFP abnormalities has been established. Purpose To investigate whether MRI-based three-dimensional texture analysis of IPFP abnormalities could help predict incident radiographic KOA. Materials and Methods In this prospective nested case-control study, 690 participants whose knees were at risk for KOA were included from the Pivotal Osteoarthritis Initiative MRI Analyses incident osteoarthritis cohort. All knees had a Kellgren-Lawrence grade of 1 or less at baseline. During the 4-year follow-up, case participants were matched 1:1 to control participants, with incident radiographic KOA as the outcome. MRI scans were segmented at the incident time point of KOA (hereafter, P0), 1 year before P0 (hereafter, P-1), and baseline. MRI-based three-dimensional texture analysis was performed to extract IPFP texture features. Least absolute shrinkage and selection operator and multivariable logistic regressions were applied in the development cohort and evaluated in the test cohort. The area under the receiver operating characteristic curve (AUC) was used to evaluate the discriminative value of the clinical score, IPFP texture score, and MRI Osteoarthritis Knee Score. Results Participants were allocated to development (n = 500, 340 women; mean age, 60 years) and test (n = 190, 120 women; mean age, 61 years) cohorts. In both cohorts, IPFP texture scores (AUC ≥0.75 for all) showed greater discrimination than clinical scores (AUC ≤0.69 for all) at baseline, P-1, and P0, with significant differences in pairwise comparisons (P ≤ .002 for all). Greater predictive and concurrent validities of IPFP texture scores (AUC ≥0.75 for all) compared with MRI Osteoarthritis Knee Scores (AUC ≤0.66 for all) were also demonstrated (P < .001 for all). Conclusion MRI-based three-dimensional texture of the infrapatellar fat pad was associated with future development of knee osteoarthritis. ClinicalTrials.gov registration no.: NCT00080171 © RSNA, 2022 Online supplemental material is available for this article. See also the editorial by Fischer in this issue.

Dataset Information

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

Publications

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

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