Blockage of Osteopontin-Integrin β3 Signaling in Infrapatellar Fat Pad Attenuates Osteoarthritis in Mice.
Bingyang DaiYuwei ZhuXu LiZuru LiangShunxiang XuShian ZhangZhe ZhangShanshan BaiWenxue TongMingde CaoYe LiXiaobo ZhuWei LiuYuantao ZhangLiang ChangPatrick Shu-Hang YungKevin Ki-Wai HoJiankun XuTo NgaiLing QinPublished in: Advanced science (Weinheim, Baden-Wurttemberg, Germany) (2023)
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.
Keyphrases
- knee osteoarthritis
- cancer therapy
- high fat diet induced
- adipose tissue
- rheumatoid arthritis
- healthcare
- oxidative stress
- type diabetes
- cell adhesion
- total knee arthroplasty
- bone mineral density
- extracellular matrix
- mouse model
- metabolic syndrome
- cell migration
- signaling pathway
- skeletal muscle
- body composition
- mesenchymal stem cells
- tissue engineering
- smoking cessation
- cell therapy
- induced pluripotent stem cells