Dalian Medical University, Dalian 116044, China.
Department of Orthopedics, Northern Jiangsu People's Hospital Affiliated to Yangzhou University, Yangzhou 225000, China.
Oxid Med Cell Longev. 2022 Jul 20;2022:9468040. doi: 10.1155/2022/9468040. eCollection 2022.
Osteoarthritis (OA) has been reported as a progressive disease in the elderly, primarily characterized by degenerated articular cartilage. There has been no satisfactory drug for the treatment of OA. DL-3-n-butylphthalide (NBP), a small molecule compound extracted from celery seeds, may have antiapoptotic, antioxidant, and anti-inflammatory activities in numerous studies. However, the effects of NBP on OA and its mechanisms have been rarely reported. In this study, the effect of NBP on OA in vitro and in vivo and its possible mechanism were investigated. The results showed that NBP injection into the knee joint inhibited osteoarthritis development in a rat model of osteoarthritis induced by DMM+ACLT. NBP could increase the expressions of extracellular matrix-related components (such as type II collagen, aggrecan, proteoglycan 4, and SRY-box 9) in human osteoarthritic chondrocytes and cartilage explants. Moreover, NBP promoted the expressions of SOD and CAT. NBP upregulated the expression of FoxO3a by inhibiting the PI3K/AKT pathway, which subsequently inhibited the apoptosis of human OA chondrocytes. In conclusion, NBP promotes cartilage extracellular matrix synthesis and inhibits osteoarthritis development and the underlying mechanism related to the activation of FoxO3a.
骨关节炎（OA）在老年人中被报道为一种进行性疾病，主要表现为关节软骨退化。目前尚无治疗 OA 的满意药物。DL-3-正丁基苯酞（NBP）是从小麦草籽中提取的一种小分子化合物，在许多研究中具有抗凋亡、抗氧化和抗炎作用。然而，NBP 对 OA 的作用及其机制很少有报道。在这项研究中，研究了 NBP 对 OA 的体内外作用及其可能的机制。结果表明，NBP 注射到膝关节中抑制了 DMM+ACLT 诱导的 OA 大鼠模型中骨关节炎的发展。NBP 可以增加人 OA 软骨细胞和软骨外植体中细胞外基质相关成分（如 II 型胶原、聚集蛋白聚糖、蛋白聚糖 4 和性别决定区 Y 框 9）的表达。此外，NBP 促进 SOD 和 CAT 的表达。NBP 通过抑制 PI3K/AKT 通路上调 FoxO3a 的表达，从而抑制人 OA 软骨细胞的凋亡。总之，NBP 促进软骨细胞外基质的合成，抑制骨关节炎的发展，其潜在机制与 FoxO3a 的激活有关。
