Wang Xinwei, Wang Danbi, Xia Peng, Cheng Kai, Wang Qi, Wang Xiaoju, Lin Qiang, Song Jiulong, Chen Anliang, Li Xueping
Department of Rehabilitation Medicine, Nanjing First Hospital, Nanjing Medical University, Nanjing, China.
Bone Joint Res. 2021 Oct;10(10):693-703. doi: 10.1302/2046-3758.1010.BJR-2021-0162.R3.
To evaluate the effect of ultrasound-targeted simvastatin-loaded microbubble destruction (UTMD ) for alleviation of the progression of osteoarthritis (OA) in rabbits through modulation of the peroxisome proliferator-activated receptor (PPARγ).
In vitro, OA chondrocytes were treated with ultrasound (US), US-targeted microbubble destruction (UTMD), simvastatin (SV), and UTMD on alternate days for four weeks. Chondrocytes were also treated with PPARγ inhibitor, PPARγ inhibitor+ UTMD , and UTMD . The cholesterol efflux rate and triglyceride levels were measured using an assay kit and oil red O staining, respectively. In vivo, the OA rabbits were treated with a single intra-articular injection of UTMD, SV, and UTMD every seven days for four weeks. Cartilage histopathology was assessed by safranin-O staining and the Mankin score. Total cholesterol (TC) and high-density lipoprotein-cholesterol (HDL-C) in rabbit knee synovial fluid were detected by enzyme-marker assay. Aggrecan, collagen II, and PPARγ expression levels were analyzed by Western blotting (WB).
In vitro, UTMD significantly increased the cholesterol efflux rate and aggrecan, collagen II, and PPARγ levels in OA chondrocytes; these effects were blocked by the PPARγ inhibitor. In vivo, UTMD significantly increased aggrecan, collagen II, PPARγ, and HDL-C levels, while TC levels and Mankin scores were decreased compared with the UTMD, SV, OA, and control groups.
UTMD promotes cartilage extracellular matrix synthesis by modulating the PPARγ-mediated cholesterol efflux pathway in OA rabbits. Cite this article: 2021;10(10):693-703.
通过调节过氧化物酶体增殖物激活受体（PPARγ），评估超声靶向微泡破坏技术（UTMD）负载辛伐他汀减轻兔骨关节炎（OA）进展的效果。
体外实验中，OA软骨细胞每隔一天分别接受超声（US）、超声靶向微泡破坏技术（UTMD）、辛伐他汀（SV）以及UTMD负载辛伐他汀处理，持续四周。软骨细胞还接受了PPARγ抑制剂、PPARγ抑制剂+UTMD负载辛伐他汀以及UTMD负载辛伐他汀处理。分别使用检测试剂盒和油红O染色法测量胆固醇流出率和甘油三酯水平。体内实验中，OA兔每隔七天接受一次关节腔内注射UTMD、SV以及UTMD负载辛伐他汀，持续四周。通过番红O染色和曼金评分评估软骨组织病理学。采用酶标法检测兔膝关节滑液中的总胆固醇（TC）和高密度脂蛋白胆固醇（HDL-C）。通过蛋白质免疫印迹法（WB）分析聚集蛋白聚糖、Ⅱ型胶原蛋白和PPARγ的表达水平。
体外实验中，UTMD负载辛伐他汀显著提高了OA软骨细胞的胆固醇流出率以及聚集蛋白聚糖、Ⅱ型胶原蛋白和PPARγ水平；这些作用被PPARγ抑制剂阻断。体内实验中，与UTMD、SV、OA和对照组相比，UTMD负载辛伐他汀显著提高了聚集蛋白聚糖、Ⅱ型胶原蛋白、PPARγ和HDL-C水平，同时降低了TC水平和曼金评分。
UTMD负载辛伐他汀通过调节PPARγ介导的胆固醇流出途径促进OA兔软骨细胞外基质合成。引用本文：2021；10（10）：693-703。
