Blockage of Osteopontin-Integrin β3 Signaling in Infrapatellar Fat Pad Attenuates Osteoarthritis in Mice.
Blockage of Osteopontin-Integrin β3 Signaling in Infrapatellar Fat Pad Attenuates Osteoarthritis in Mice.
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DOI：
10.1002/advs.202300897
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发表时间：
2023-08
期刊：
影响因子：
--
通讯作者：
Qin L
中科院分区：
文献类型：
--
作者：
Dai B;Zhu Y;Li X;Liang Z;Xu S;Zhang S;Zhang Z;Bai S;Tong W;Cao M;Li Y;Zhu X;Liu W;Zhang Y;Chang L;Yung PS;Ki-Wai Ho K;Xu J;Ngai T;Qin L
骨关节炎(OA)的认识如今已从一种局限性软骨疾病扩展到一种多因素疾病。尽管最近的研究报道了膝盖骨下脂肪垫(IPFP)可以引发膝关节炎症，但是IPFP在膝骨性关节炎进展中的作用机制仍未明确。在这里，骨桥蛋白和整合素β3信号通路在人和小鼠的骨性关节炎标本中都被发现。进一步证明IPFP来源的骨桥蛋白参与了骨性关节炎的进展，包括活化的基质金属肽酶9参与软骨细胞肥大，整合素β3参与IPFP纤维化。在这些发现的推动下，制造了一种可注射的纳米凝胶来提供针对整合素的siRNACD61(RGD−纳米凝胶/siRNACD61)的持续释放。RGD型−纳米凝胶具有良好的生物相容性和体内、外靶向能力。局部注射RGD−纳米凝胶/siRNACD61可显著减轻骨关节炎小鼠软骨退变，抑制潮标推进，减少软骨下骨量。综上所述，本研究为开发RGDOPN纳米凝胶/siRNACD61治疗方法提供了一条途径，通过阻断−整合素IPFP中的β3信号来减缓OA的进展。IPFP异常相关的OPN在包括关节软骨细胞肥大和IPFP纤维化在内的骨性关节炎的进展中起着至关重要的作用。RGD-Nanogel/siRNA CD61系统可以有效地减轻软骨侵蚀和IPFP炎症，抑制潮标的进展，减少软骨下骨量，因此可以作为一种创新的治疗策略来缓解骨性关节炎的进展。
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. IPFP aberration‐associated OPN plays a crucial role in OA progression, including articular chondrocyte hypertrophy and IPFP fibrosis. The RGD‐Nanogel/siRNA Cd61 system effectively attenuates the cartilage erosion and IPFP inflammation, suppresses the advancement of tidemark, and reduces the subchondral trabecular bone mass, therefore may serve as an innovative therapeutic strategy to mitigate OA progression.
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影响因子：
27.4
作者：
Atukorala I;Kwoh CK;Guermazi A;Roemer FW;Boudreau RM;Hannon MJ;Hunter DJ
通讯作者：
Hunter DJ
影响因子：
12.8
作者：
Cho Y;Jeong S;Kim H;Kang D;Lee J;Kang SB;Kim JH
通讯作者：
Kim JH
DOI：
10.1002/jor.23872
发表时间：
2018-02-17
期刊：
Journal of orthopaedic research : official publication of the Orthopaedic Research Society
影响因子：
--
作者：
Gilbert SJ;Bonnet CS;Stadnik P;Duance VC;Mason DJ;Blain EJ
通讯作者：
Blain EJ
影响因子：
33.7
作者：
Apparailly, Florence;Jorgensen, Christian
通讯作者：
Jorgensen, Christian
影响因子：
27.4
作者：
Han, Weiyu;Aitken, Dawn;Ding, Changhai
通讯作者：
Ding, Changhai