Laboratory of Clinical Orthopedics, The Affiliated Changzhou Second People's Hospital of Nanjing Medical University, Changzhou, China.
Bone Disease Research and Clinical Rehabilitation Center, Changzhou Medical Center, NanjingMedicalUniversity, Changzhou, China.
Phytother Res. 2023 Nov;37(11):5394-5406. doi: 10.1002/ptr.7979. Epub 2023 Aug 26.
Osteoarthritis (OA) is a common degenerative joint disease, which is characterized by wear of articular cartilage and narrow joint space, resulting in joint movement disorder. At present, accurate molecular mechanisms and effective interventions are still being explored. Here, we propose that angelica sinensis polysaccharide (ASP) alleviates OA progression by activating peroxisome proliferator-activated receptor gamma (PPARγ). Therapeutic effect of ASP improving mitochondrial metabolism of OA chondrocytes was evaluated in vitro and in vivo, respectively. During cell experiments, the concentration and time response of tert butyl hydroperoxide (TBHP) and ASP were determined by cell viability. Apoptosis was detected by flow cytometry. Mitochondrial metabolism was detected by reactive oxygen species (ROS), mitochondrial membrane potential (MMP), release of cytochrome C, adenosine triphosphate (ATP) production, and superoxide dismutase 2 (SOD2) activity. Expressions of Aggrecan, collagen type II (Col2a1), PPARγ, and SOD2 were detected by qRT-PCR and western blot. In animal experiments, we detected cell apoptosis and target protein expression separately through terminal deoxynucleotidyl transferase dUTP nick end-labeling (TUNEL) staining and immunohistochemistry. Pretreatment of ASP significantly activated PPARγ and SOD2 in rat chondrocytes incubated with TBHP, cleared ROS, improved mitochondrial metabolism, increased chondrocytes viability, and alleviated chondrocytes apoptosis. In vivo, the administration of ASP could effectively ameliorate cartilage degeneration in OA rats, promote extracellular matrix synthesis, and decelerate the progress of OA. Our research identifies the role of ASP in mitochondrial metabolism of OA chondrocytes through PPARγ/SOD2/ROS pathways, which provides a new idea for the treatment of OA.
骨关节炎（OA）是一种常见的退行性关节疾病，其特征为关节软骨磨损和关节间隙变窄，导致关节运动障碍。目前，仍在探索准确的分子机制和有效的干预措施。在这里，我们提出当归多糖（ASP）通过激活过氧化物酶体增殖物激活受体γ（PPARγ）来减轻 OA 的进展。分别在体外和体内评估了 ASP 改善 OA 软骨细胞线粒体代谢的治疗效果。在细胞实验中，通过细胞活力测定确定叔丁基过氧化氢（TBHP）和 ASP 的浓度和时间反应。通过流式细胞术检测细胞凋亡。通过活性氧（ROS）、线粒体膜电位（MMP）、细胞色素 C 的释放、三磷酸腺苷（ATP）的产生和超氧化物歧化酶 2（SOD2）活性检测线粒体代谢。通过 qRT-PCR 和 Western blot 检测聚集蛋白聚糖、II 型胶原（Col2a1）、PPARγ 和 SOD2 的表达。在动物实验中，我们通过末端脱氧核苷酸转移酶 dUTP 缺口末端标记（TUNEL）染色和免疫组织化学法分别检测细胞凋亡和靶蛋白表达。ASP 预处理可显著激活 TBHP 孵育的大鼠软骨细胞中的 PPARγ 和 SOD2，清除 ROS，改善线粒体代谢，增加软骨细胞活力，减轻软骨细胞凋亡。在体内，ASP 的给药可有效改善 OA 大鼠的软骨退变，促进细胞外基质的合成，并减缓 OA 的进展。我们的研究通过 PPARγ/SOD2/ROS 途径确定了 ASP 在 OA 软骨细胞线粒体代谢中的作用，为 OA 的治疗提供了新的思路。
