Shanghai Key Laboratory of Orthopaedic Implants, Department of Orthopaedic Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People's Republic of China.
Cartilage. 2021 Dec;13(2_suppl):1041S-1053S. doi: 10.1177/19476035211038748. Epub 2021 Nov 15.
Emerging evidence has indicated that excessive reactive oxygen species (ROS) have detrimental effects on osteoarthritis (OA). This study aimed to elucidate the effects of melatonin (MT), an antioxidant indolamine secreted from the pineal gland, on chondrocyte senescence and cartilage degeneration, thereby clarifying the underlying mechanisms of ROS-induced OA pathogenesis.
Hydrogen peroxide (HO) was used to induce oxidative stress in rat chondrocytes. ROS levels were evaluated using cytometry and immunofluorescence. Cell viability was detected using the Cell Counting Kit-8 (CCK-8) assay. Western blotting and qPCR (Quantiative Real-Time Polymerase Chain Reaction) were used to examine apoptosis and autophagy. For experiments, male Sprague-Dawley rats were randomly divided into a sham-operated group, DMM (destabilization of the medial meniscus) surgery group, and surgery groups that received melatonin. Knee joints were collected and stained for histological analysis.
The data demonstrated that melatonin treatment significantly suppressed HO-induced matrix degradation and apoptosis, and maintained mitochondrial redox homeostasis. In addition, an enhancement of autophagic flux was observed through western blotting. These findings corresponded with activation of the AMPK/Foxo3 signaling pathways upon melatonin treatment. Histological staining and transmission electron microscopy (TEM) micrographs also demonstrated that melatonin alleviated cartilage ossification and chondrocyte hypertrophy .
Our results indicated that melatonin protected chondrocytes via mitochondrial redox homeostasis and autophagy. The effects of melatonin on senescence may apply to other age-related diseases. Thus, melatonin may have multiple potential therapeutic applications.
新出现的证据表明，过多的活性氧（ROS）对骨关节炎（OA）有不利影响。本研究旨在阐明褪黑素（MT），一种由松果腺分泌的抗氧化吲哚胺，对软骨细胞衰老和软骨退化的影响，从而阐明 ROS 诱导的 OA 发病机制的潜在机制。
用过氧化氢（HO）诱导大鼠软骨细胞氧化应激。使用细胞计数试剂盒-8（CCK-8）检测细胞活力。通过流式细胞术和免疫荧光法评估 ROS 水平。Western blot 和 qPCR（实时定量聚合酶链反应）用于检测细胞凋亡和自噬。雄性 Sprague-Dawley 大鼠随机分为假手术组、DMM（内侧半月板不稳定）手术组和褪黑素治疗手术组。收集膝关节并进行组织学分析。
数据表明，褪黑素治疗显著抑制了 HO 诱导的基质降解和凋亡，并维持了线粒体氧化还原平衡。此外，通过 Western blot 观察到自噬通量增强。这些发现与褪黑素处理后 AMPK/Foxo3 信号通路的激活相对应。组织学染色和透射电子显微镜（TEM）照片还表明，褪黑素减轻了软骨骨化和软骨细胞肥大。
我们的结果表明，褪黑素通过线粒体氧化还原平衡和自噬来保护软骨细胞。褪黑素对衰老的影响可能适用于其他与年龄相关的疾病。因此，褪黑素可能具有多种潜在的治疗应用。
