Long term usage of dexamethasone accelerating the initiation of osteoarthritis via enhancing the extracellular matrix calcification and apoptosis of chondrocytes
| Autor: | Ruobin Zhang, Xiaolan Du, Dali Zhang, Liang Kuang, Lin Chen, Liang Chen, Yangli Xie, Hangang Chen, Junjie Ouyang, Min Jin, Fengtao Luo, Xianding Sun, Zhenhong Ni, Huabing Qi, Siru Zhou, Bin Zhang, Qiaoyan Tan, Nan Su, Jinfan Zhang, Junlan Huang, Jing Yang, Zuqiang Wang |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
medicine.medical_specialty
biology Chemistry Autophagy Cell Biology Osteoarthritis medicine.disease Applied Microbiology and Biotechnology Chondrocyte Extracellular matrix medicine.anatomical_structure Endocrinology Proteoglycan Internal medicine polycyclic compounds medicine biology.protein Molecular Biology Protein kinase B hormones hormone substitutes and hormone antagonists Ecology Evolution Behavior and Systematics Dexamethasone Developmental Biology medicine.drug Calcification |
| Zdroj: | International Journal of Biological Sciences. 17:4140-4153 |
| ISSN: | 1449-2288 |
| Popis: | Systemic application of glucocorticoids is an essential anti-inflammatory and immune-modulating therapy for severe inflammatory or autoimmunity conditions. However, its long-term effects on articular cartilage of patients' health need to be further investigated. In this study, we studied the effects of dexamethasone (Dex) on the homeostasis of articular cartilage and the progress of destabilization of medial meniscus (DMM)-induced osteoarthritis (OA) in adult mice. Long-term administration of Dex aggravates the proteoglycan loss of articular cartilage and drastically accelerates cartilage degeneration under surgically induced OA conditions. In addition, Dex increases calcium content in calcified cartilage layer of mice and the samples from OA patients with a history of long-term Dex treatment. Moreover, long term usage of Dex results in decrease subchondral bone mass and bone density. Further studies showed that Dex leads to calcification of extracellular matrix of chondrocytes partially through activation of AKT, as well as promotes apoptosis of chondrocytes in calcified cartilage layer. Besides, Dex weakens the stress-response autophagy with the passage of time. Taken together, our data indicate that long-term application of Dex may predispose patients to OA and or even accelerate the OA disease progression development of OA patients. |
| Databáze: | OpenAIRE |
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