The anti-inflammation effect of strontium ranelate on rat chondrocytes with or without IL-1β in vitro

雷奈酸锶对有或无IL-1β的大鼠软骨细胞体外抗炎作用

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作者:Hao Yu, Yan Liu, Xiangwen Yang, Jiajing He, Qun Zhong, Xiaojing Guo

Abstract

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.

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