Alendronate promotes the gene expression of extracellular matrix mediated by SP-1/SOX-9
| Autor: | H Zhu, B Mi, Hong-Tao Yan, Yun Zhang, Lianjun Wang |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Alendronate Bone Density Conservation Agents Chemistry Health Toxicology and Mutagenesis Gene Expression Articular cartilage General Medicine Osteoarthritis Toxicology medicine.disease Extracellular Matrix Cell biology Extracellular matrix 03 medical and health sciences Chondrocytes 030104 developmental biology 0302 clinical medicine 030220 oncology & carcinogenesis Gene expression medicine Humans Cells Cultured |
| Zdroj: | Human & Experimental Toxicology. 40:1173-1182 |
| ISSN: | 1477-0903 0960-3271 |
| Popis: | Background and purpose: Osteoarthritis (OA) is a disease with significant degenerative changes of articular cartilage, which is reported to be closely related to the integrity of chondrocytes extracellular matrix (ECM). Alendronate belongs to the family of bisphosphonates with promising cartilage repair function. In the present study, the effects of Alendronate on the gene expression of chondrocytes ECM and the potential mechanism will be investigated to explore the potential therapeutic property of Alendronate on OA. Methods: Human SW1353 chondrocytes were stimulated with 1 and 2 μM Alendronate for 12 h. The gene expression of Col2α1, COL9α2, and Acan in the treated chondrocytes was determined by qRT-PCR. QRT-PCR and western blot analysis were used to evaluate the expression level of SOX-9 in the treated chondrocytes. The expression level of SP-1 was checked by qRT-PCR and immunostaining. SiRNA against SP-1 was transfected into chondrocytes to knockdown the expression of SP-1. The levels of p-ERK1/2 and total ERK1/2 were examined using western blot analysis. TNF-α was used to induce an OA-like in vitro model in the chondrocytes for therapeutic evaluations. Results: Treatment with Alendronate increased the levels of ECM related genes ( Col2α1, COL9α2, and Acan) in a dose-dependent manner through increasing the expression of SOX-9, a central regulator of ECM genes. Additionally, our findings demonstrate that the effects of Alendronate in the expression of SOX-9 are mediated by SP-1 as silencing of SP-1 abolished these effects. Notably, Alendronate increased the phosphorylation of ERK1/2 and inhibition of ERK1/2 using its specific inhibitor U0126 blocked the expression of SP-1. Finally, we found that treatment with Alendronate could rescue TNF-α-induced reduction of Col2α1, COL9α2, Acan and SOX-9. Conclusion: Our data indicated that Alendronate might promote the gene expression of extracellular matrix through SOX-9 mediated by the ERK1/2/SP1 signaling pathway. |
| Databáze: | OpenAIRE |
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