Int J Biol Sci 2021; 17(15):4140-4153. doi:10.7150/ijbs.64152 This issue

Research Paper

Long term usage of dexamethasone accelerating the initiation of osteoarthritis via enhancing the extracellular matrix calcification and apoptosis of chondrocytes

Liang Chen1,2, Zhenhong Ni1, Junlan Huang1, Ruobin Zhang1, Jinfan Zhang1, Bin Zhang1, Liang Kuang1, Xianding Sun1, Dali Zhang1, Nan Su1, Huabing Qi1, Jing Yang1, Min Jin1, Fengtao Luo1, Hangang Chen1, Siru Zhou1, Xiaolan Du1, Junjie Ouyang1, Zuqiang Wang1, Yangli Xie1✉, Qiaoyan Tan1✉, Lin Chen1✉

1. Center of Bone Metabolism and Repair, Department of Wound Repair and Rehabilitation Medicine, State Key Laboratory of Trauma, Burns and Combined Injury, Trauma Center, Research Institute of Surgery, Daping Hospital, Army Medical University, Chongqing, China.
2. Department of orthopedic, Daping Hospital, Army Medical University, Chongqing, China.

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Citation:
Chen L, Ni Z, Huang J, Zhang R, Zhang J, Zhang B, Kuang L, Sun X, Zhang D, Su N, Qi H, Yang J, Jin M, Luo F, Chen H, Zhou S, Du X, Ouyang J, Wang Z, Xie Y, Tan Q, Chen L. Long term usage of dexamethasone accelerating the initiation of osteoarthritis via enhancing the extracellular matrix calcification and apoptosis of chondrocytes. Int J Biol Sci 2021; 17(15):4140-4153. doi:10.7150/ijbs.64152. Available from https://www.ijbs.com/v17p4140.htm

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Abstract

Graphic abstract

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.

Keywords: dexamethasone, articular cartilage, calcification, apoptosis, AKT