Departments of Orthopedics, The First Hospital of Yangtze University, Jingzhou, China.
Departments of Orthopedics, The Jiangling County People's Hospital, Jingzhou, China.
Aging (Albany NY). 2022 Aug 24;14(16):6716-6726. doi: 10.18632/aging.204245.
Estrogen and its receptor play a positive role in the development of osteoarthritis (OA). Psoralen is a plant-derived estrogen analog. This study aimed to verify whether psoralen inhibits OA through an estrogen-like effect. First, human primary chondrocytes in the late stage of OA were extracted to complete collagen type II immunofluorescence staining and cell proliferation experiments. Subsequently, estrogen, psoralen and estrogen receptor antagonists were co-cultured with OA chondrocytes, and RT-PCR was performed to detect the gene expression. A rabbit OA model was subsequently made by anterior cruciate ligament transection (ACLT). They were set as Sham group, OA group and Psoralen group, respectively. The articular cartilage samples were taken after 5 weeks of treatment, and the effect was observed by gross observation, histological staining, micro-CT scanning of subchondral bone. The results of cellular experiments displayed that the cultured cells were positive for collagen II fluorescence staining and 12 μg/mL psoralen was selected as the optimal concentration. In addition, psoralen had effects similar to estrogen, promoting the expression of estrogen tar-get genes CTSD, PGR and TFF1 and decreasing the expression of the inflammation-related gene TNF- α, IL-1β and IL-6. The effect of psoralen was blocked after the use of an estrogen receptor antagonist. Further animal experiments indicated that the psoralen group showed less destruction of cartilage tissue and decreased OASRI scores compared with the OA group. A subchondral bone CT scan demonstrated that psoralen significantly increased subchondral bone mineral density (BMD), trabecular thickness and trabecular number and decreased trabecular separation. In summary, psoralen inhibits the inflammatory production of chondrocytes, which is related to estrogen-like effect, and can be used to attenuate the progression of OA.
雌激素及其受体在骨关节炎（OA）的发展中发挥积极作用。补骨脂素是一种植物衍生的雌激素类似物。本研究旨在验证补骨脂素是否通过类雌激素作用抑制 OA。首先，提取晚期 OA 患者的人原代软骨细胞，完成 II 型胶原免疫荧光染色和细胞增殖实验。随后，将雌激素、补骨脂素和雌激素受体拮抗剂与 OA 软骨细胞共培养，进行 RT-PCR 检测基因表达。然后通过前交叉韧带切断（ACLT）制作兔 OA 模型。分别设为 Sham 组、OA 组和补骨脂素组。治疗 5 周后取关节软骨样本，通过大体观察、组织学染色、软骨下骨 micro-CT 扫描观察疗效。细胞实验结果显示，培养细胞 II 型胶原荧光染色阳性，选择 12 μg/mL 补骨脂素为最佳浓度。此外，补骨脂素具有类似雌激素的作用，促进雌激素靶基因 CTSD、PGR 和 TFF1 的表达，降低炎症相关基因 TNF-α、IL-1β 和 IL-6 的表达。使用雌激素受体拮抗剂后，补骨脂素的作用被阻断。进一步的动物实验表明，与 OA 组相比，补骨脂素组软骨组织破坏较少，OASRI 评分降低。软骨下骨 CT 扫描显示，补骨脂素可显著增加软骨下骨骨密度（BMD）、骨小梁厚度和数量，减少骨小梁分离。总之，补骨脂素抑制软骨细胞的炎症产生，与类雌激素作用有关，可用于减轻 OA 的进展。
