雷奈酸锶对有或无白细胞介素-1β的大鼠软骨细胞的抗炎作用。
The anti-inflammation effect of strontium ranelate on rat chondrocytes with or without IL-1β .
作者信息
Yu Hao, Liu Yan, Yang Xiangwen, He Jiajing, Zhong Qun, Guo Xiaojing
机构信息
Department of Prosthodontics, Shanghai Stomatological Hospital, Huangpu, Shanghai 200001, P.R. China.
Shanghai Key Laboratory of Craniomaxillofacial Development and Diseases, Fudan University, Huangpu, Shanghai 200001, P.R. China.
出版信息
Exp Ther Med. 2022 Mar;23(3):208. doi: 10.3892/etm.2022.11131. Epub 2022 Jan 7.
Temporomandibular joint osteoarthritis (TMJ-OA) is a common disease with a high level of inflammation in the joint micro-environment and cartilage degradation. Anti-inflammation and cartilage regeneration are the key therapies for TMJ-OA, but currently, there are no novel medicines or treatments that can control its pathogenic progression. Strontium ranelate (SrR) is an anti-osteoporosis drug and is now considered a promising anti-OA drug, but the anti-inflammatory effect of SrR remains to be elucidated. In the present study, the anti-inflammatory effect of SrR in a normal or high IL-1β environment was observed. Cell viability under the treatment of SrR was tested using Cell Counting Kit-8. Toluidine blue staining, immunofluorescence staining, hydroxyproline assay, PCR assay and western blotting were used to detect the expression of collagen (Col)II, proteoglycans (PG) and aggrecan as a reflection of extracellular matrix synthesis and MMP-9,13 hydroxyproline was used as an inflammation indicator. IL-1β of 10 ng/ml was added to the culture medium as inflammation environment and the tests of those biomarkers were done again. Then, the changes in β-catenin were also studied by immunofluorescence staining, PCR assay and western blotting to explore the possible involvement of the Wnt/β-catenin pathway. The results showed a significant inhibition of MMP-9, MMP-13, β-catenin and promotion of Col-II, PG and aggrecan in normal chondrocytes. The presence of IL-1β markedly upregulated the expression of MMP-9, MMP-13 and β-catenin while suppressing Col-II and PG and SrR partially reversed this trend. In conclusion, SrR decreased MMPs but promoted Col-II, aggrecan and PG synthesis in rat chondrocytes with or without the presence of IL-1β and SrR attenuated the IL-1β-induced increase in β-catenin, thus reducing the inflammatory reaction.
颞下颌关节骨关节炎(TMJ - OA)是一种常见疾病,其关节微环境存在高水平炎症且伴有软骨降解。抗炎和软骨再生是TMJ - OA的关键治疗方法,但目前尚无能够控制其致病进程的新型药物或治疗手段。雷奈酸锶(SrR)是一种抗骨质疏松药物,现被认为是一种有前景的抗骨关节炎药物,但其抗炎作用仍有待阐明。在本研究中,观察了SrR在正常或高白细胞介素 - 1β(IL - 1β)环境中的抗炎作用。使用细胞计数试剂盒 - 8检测SrR处理下的细胞活力。采用甲苯胺蓝染色、免疫荧光染色、羟脯氨酸测定、聚合酶链反应(PCR)测定和蛋白质印迹法检测Ⅱ型胶原蛋白(Col)、蛋白聚糖(PG)和聚集蛋白聚糖的表达,以反映细胞外基质合成情况,同时将羟脯氨酸用作炎症指标。向培养基中添加10 ng/ml的IL - 1β作为炎症环境,并再次进行这些生物标志物的检测。然后,还通过免疫荧光染色、PCR测定和蛋白质印迹法研究β - 连环蛋白的变化,以探索Wnt/β - 连环蛋白信号通路可能的参与情况。结果显示,在正常软骨细胞中,SrR显著抑制基质金属蛋白酶 - 9(MMP - 9)、基质金属蛋白酶 - 13(MMP - 13)和β - 连环蛋白,同时促进Col - II、PG和聚集蛋白聚糖的表达。IL - 1β的存在显著上调MMP - 9、MMP - 13和β - 连环蛋白的表达,同时抑制Col - II和PG,而SrR部分逆转了这一趋势。总之,无论有无IL - 1β存在,SrR均可降低大鼠软骨细胞中的基质金属蛋白酶水平,但促进Col - II、聚集蛋白聚糖和PG的合成,并且SrR减弱了IL - 1β诱导的β - 连环蛋白增加,从而减轻炎症反应。