局部递送改性柑橘果胶 - 半乳凝集素-3 抑制剂对关节软骨缺损修复具有预期的抗炎作用和意想不到的促进再生作用。
Locally delivered modified citrus pectin - a galectin-3 inhibitor shows expected anti-inflammatory and unexpected regeneration-promoting effects on repair of articular cartilage defect.
机构信息
The Key Laboratory of Biomedical Material of Tianjin, Biomedical Barriers Research Center, Chinese Academy of Medical Sciences & Peking Union Medical College Institute of Biomedical Engineering, Tianjin, 300192, PR, China.
School of Chemistry and Chemical Engineering, Tianjin University of Technology, Tianjin, 300384, PR, China.
出版信息
Biomaterials. 2022 Dec;291:121870. doi: 10.1016/j.biomaterials.2022.121870. Epub 2022 Nov 1.
Treating the concomitant inflammation in the process of injury and repair, and simultaneously promoting cartilage regeneration is very important for the repair of articular cartilage (AC) defects. Nevertheless, this remains a massive challenge. To address this issue, a collagen membrane-based modified citrus pectin (MCP) delivery system (MCP-C) was developed in this study by targeting galectin-3 (Gal-3), an upstream proinflammatory factor. As expected, MCP shows anti-inflammatory effects; it downregulates the expressions of IL-1β, MMP13, Gal-3, and COL1A2, inhibits the degenerative effects of Gal-3 on chondrocytes in vitro, and protects chondrocytes from degeneration and death in vivo. Unexpectedly, MCP promotes the proliferation of chondrocytes, upregulates the expression of COL2A1 and SOX9 in the chondrocytes in vitro, and enhances the repair of AC defect in rabbit knee, especially MCP-C with a complete release of the loading amount of approximately 500 μg/cm in a day. Mechanistically, MCP upregulates the expressions of multiple endogenous growth factors for chondrogenesis via the transcriptome sequencing of MCP-treated chondrocytes, and downregulates the expressions of various inflammatory factors. These findings demonstrate that locally delivered MCP can simultaneously modulate both regenerative and inflammatory responses, and can enhance the repair of AC defects.
在损伤和修复过程中治疗伴随的炎症,同时促进软骨再生,对于关节软骨(AC)缺损的修复非常重要。然而,这仍然是一个巨大的挑战。为了解决这个问题,本研究通过靶向半乳糖凝集素-3(Gal-3)这一上游促炎因子,开发了一种基于胶原膜的改性柑橘果胶(MCP)递送系统(MCP-C)。正如预期的那样,MCP 表现出抗炎作用;它下调了 IL-1β、MMP13、Gal-3 和 COL1A2 的表达,抑制了 Gal-3 对体外软骨细胞的退行性作用,并保护软骨细胞免于体内退化和死亡。出乎意料的是,MCP 促进了软骨细胞的增殖,上调了体外软骨细胞中 COL2A1 和 SOX9 的表达,并增强了兔膝关节 AC 缺损的修复,特别是在一天内完全释放约 500μg/cm 加载量的 MCP-C。从机制上讲,MCP 通过对 MCP 处理的软骨细胞进行转录组测序,上调了多种软骨发生的内源性生长因子的表达,并下调了各种炎症因子的表达。这些发现表明,局部递送的 MCP 可以同时调节再生和炎症反应,并增强 AC 缺损的修复。