Shen Haotian, Cheng Linxiang, Zheng Qiangqiang, Liu Wenduo, Wang Yue
Department of Orthopedic Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China.
Department of Orthopedic Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China.
Acta Biomater. 2022 Oct 15;152:440-452. doi: 10.1016/j.actbio.2022.09.007. Epub 2022 Sep 13.
Tendinopathy is a common disorder that leads to pain and impaired quality of life. Recent studies revealed that osteogenic differentiation of tendon stem/progenitor cells (TSPCs) played an important role in the pathogenesis of tendon calcification and tendinopathy. In this study, we found that the growth hormone-releasing hormone agonist (GA) can prevent matrix degradation and osteogenic differentiation in TSPCs. As oxidative stress is a key factor in the osteogenic differentiation of TSPCs, we used bovine serum albumin/heparin nanoparticles (BHNPs), which have biocompatibility and drug loading capacity, to scavenge reactive oxygen species (ROS) and achieve sustained release of GA at the site of inflammation. The newly developed BHNPs@GA had a synergetic effect on reducing ROS production in TSPCs. In addition, BHNPs@GA effectively inhibited tendon calcification and promoted collagen formation in a rat model of tendinopathy. Focusing on the ROS underlying the differentiation and dedifferentiation of TSPCs, this work demonstrated that sustained release of GA targeting ROS and ectopic ossification is a practical therapeutic strategy for treating tendinopathy. STATEMENT OF SIGNIFICANCE: Osteogenic differentiation of tendon stem/progenitor cells (TSPCs) plays an important role in the pathogenesis of ectopic calcification in tendinopathy. In this study, we found that growth hormone-releasing hormone agonist (GA) can reduce reactive oxygen species (ROS) production and adjust TSPCs differentiation. Bovine serum albumin/heparin nanoparticles (BHNPs) were developed to encapsulate GA and achieve sustained release of GA at the site of inflammation. The developed compound, BHNPs@GA, with a synergistic effect of inhibiting ROS and thus, can effectively adjust TSPCs differentiation, inhibit tendon calcification, and promote collagen formation in tendinopathy. This study highlighted the role of ROS underlying the differentiation and dedifferentiation of TSPCs in tendinopathy, and findings may help to identify new therapeutic targets and develop novel strategy for treating tendinopathy.
肌腱病是一种常见疾病，会导致疼痛并降低生活质量。最近的研究表明，肌腱干/祖细胞（TSPCs）的成骨分化在肌腱钙化和肌腱病的发病机制中起重要作用。在本研究中，我们发现生长激素释放激素激动剂（GA）可以防止TSPCs中的基质降解和成骨分化。由于氧化应激是TSPCs成骨分化的关键因素，我们使用具有生物相容性和药物负载能力的牛血清白蛋白/肝素纳米颗粒（BHNPs）来清除活性氧（ROS）并在炎症部位实现GA的持续释放。新开发的BHNPs@GA对减少TSPCs中的ROS产生具有协同作用。此外，BHNPs@GA在肌腱病大鼠模型中有效抑制了肌腱钙化并促进了胶原蛋白的形成。着眼于TSPCs分化和去分化背后的ROS，这项工作表明，靶向ROS和异位骨化的GA持续释放是治疗肌腱病的一种切实可行的治疗策略。重要性声明：肌腱干/祖细胞（TSPCs）的成骨分化在肌腱病异位钙化的发病机制中起重要作用。在本研究中，我们发现生长激素释放激素激动剂（GA）可以减少活性氧（ROS）的产生并调节TSPCs的分化。开发了牛血清白蛋白/肝素纳米颗粒（BHNPs）来包裹GA并在炎症部位实现GA的持续释放。所开发的化合物BHNPs@GA具有抑制ROS的协同作用，因此可以有效调节TSPCs的分化，抑制肌腱钙化，并促进肌腱病中胶原蛋白的形成。这项研究突出了ROS在肌腱病中TSPCs分化和去分化中的作用，研究结果可能有助于确定新的治疗靶点并开发治疗肌腱病的新策略。
