Li Zhen, Chen Zhenyue, Chen Jiayi, Liu Zhutong, Li Zehui, Sun He, Wang Xiaochao, Wei Jinqiang, Cao Xuewei, Zheng Decai
The Second Clinical College of Guangzhou, University of Chinese Medicine, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangdong Provincial Hospital of Chinese Medicine, Guangzhou, 510120, Guangdong, China.
The First Clinical College of Guangzhou, University of Chinese Medicine, Guangzhou, 510405, Guangdong, China.
Chin Med. 2023 Apr 19;18(1):42. doi: 10.1186/s13020-023-00748-2.
Osteoarthritis (OA) is a chronic degenerative joint disease characterized by loss of joint function, which seriously reduces the quality of life of the elderly and imposes a heavy socioeconomic burden worldwide. Monotropein (MON), the main active ingredient of Morinda officinalis F.C. How, has exhibited therapeutic effects in different disease models. However, its potential effects on chondrocytes in an arthritic model remain unclear. This study aimed to evaluate the effects of MON in chondrocytes and a mouse model of OA, and explore the potential mechanisms.
Murine primary chondrocytes were pretreated with 10 ng/ml interleukin (IL)-1β for 24 h to establish an in vitro model of OA, and then treated with different concentrations of MON (0, 25, 50 and 100 μM) for 24 h. The proliferation of the chondrocytes was assayed using ethynyl-deoxyuridine (EdU) staining. Immunofluorescence staining, western blotting and TUNEL staining were performed to assess the effects of MON on cartilage matrix degradation, apoptosis and pyroptosis. The mouse model of OA was constructed by surgical destabilization of the medial meniscus (DMM), and the animals were randomly divided into the sham-operated, OA and OA + MON groups. Following OA induction, the mice were given intraarticular injection of 100 μM MON or equal volume of normal saline twice a week for 8 weeks. The effects of MON on cartilage matrix degradation, apoptosis and pyroptosis were assessed as indicated.
MON significantly accelerated the proliferation of chondrocytes, and inhibited cartilage matrix degradation, apoptosis and pyroptosis in the IL-1β-stimulated cells by blocking the nuclear factor-kappa B (NF-κB) signaling pathway. In the mouse model as well, MON treatment alleviated OA progression and promoted cartilage repair by inhibiting cartilage matrix degradation, and chondrocyte apoptosis and pyroptosis through the inactivation of the NF-κB signaling pathway. Furthermore, the MON-treated arthritic mice exhibited better articular tissue morphology and lower OARSI scores.
MON alleviated OA progression by inhibiting cartilage matrix degradation, and the apoptosis and pyroptosis of chondrocytes via NF-κB pathway inactivation, and is a promising alternative for the treatment of OA.
骨关节炎（OA）是一种以关节功能丧失为特征的慢性退行性关节疾病，严重降低了老年人的生活质量，并在全球范围内造成了沉重的社会经济负担。巴戟天素（MON）是巴戟天的主要活性成分，已在不同疾病模型中显示出治疗作用。然而，其在关节炎模型中对软骨细胞的潜在作用仍不清楚。本研究旨在评估MON对软骨细胞和OA小鼠模型的影响，并探讨其潜在机制。
将小鼠原代软骨细胞用10 ng/ml白细胞介素（IL）-1β预处理24小时以建立OA体外模型，然后用不同浓度的MON（0、25、50和100 μM）处理24小时。使用乙炔基脱氧尿苷（EdU）染色检测软骨细胞的增殖。进行免疫荧光染色、蛋白质印迹和TUNEL染色以评估MON对软骨基质降解、凋亡和焦亡的影响。通过内侧半月板手术失稳（DMM）构建OA小鼠模型，并将动物随机分为假手术组、OA组和OA + MON组。诱导OA后，小鼠每周两次关节内注射100 μM MON或等体积生理盐水，共8周。如前所述评估MON对软骨基质降解、凋亡和焦亡的影响。
MON通过阻断核因子-κB（NF-κB）信号通路，显著促进了软骨细胞的增殖，并抑制了IL-1β刺激细胞中的软骨基质降解、凋亡和焦亡。在小鼠模型中，MON治疗也通过抑制软骨基质降解以及通过NF-κB信号通路的失活抑制软骨细胞凋亡和焦亡，减轻了OA进展并促进了软骨修复。此外，接受MON治疗的关节炎小鼠表现出更好的关节组织形态和更低的OARSI评分。
MON通过抑制软骨基质降解以及通过NF-κB途径失活抑制软骨细胞的凋亡和焦亡，减轻了OA进展，是一种有前途的OA治疗替代药物。
