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

被引：26

作者：

Chen, Liang ^{[1
,2
]}

Ni, Zhenhong ^{[1
]}

Huang, Junlan ^{[1
]}

Zhang, Ruobin ^{[1
]}

Zhang, Jinfan ^{[1
]}

Zhang, Bin ^{[1
]}

Kuang, Liang ^{[1
]}

Sun, Xianding ^{[1
]}

Zhang, Dali ^{[1
]}

Su, Nan ^{[1
]}

Qi, Huabing ^{[1
]}

Yang, Jing ^{[1
]}

Jin, Min ^{[1
]}

Luo, Fengtao ^{[1
]}

Chen, Hangang ^{[1
]}

Zhou, Siru ^{[1
]}

Du, Xiaolan ^{[1
]}

Ouyang, Junjie ^{[1
]}

Wang, Zuqiang ^{[1
]}

Xie, Yangli ^{[1
]}

Tan, Qiaoyan ^{[1
]}

Chen, Lin ^{[1
]}

机构：

[1] Army Med Univ, Daping Hosp, Res Inst Surg,Dept Wound Repair & Rehabil Med,Ctr, Trauma Ctr,State Key Lab Trauma Burns & Combined, 10 Changjiangzhilu Daping, Chongqing 400042, Peoples R China

[2] Army Med Univ, Daping Hosp, Dept Orthoped, Chongqing, Peoples R China

来源：

INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES | 2021年 / 17卷 / 15期

基金：

国家重点研发计划; 中国国家自然科学基金;

关键词：

dexamethasone; articular cartilage; calcification; apoptosis; AKT; CALCIFIED CARTILAGE; ARTICULAR-CARTILAGE; SUBCHONDRAL BONE; AUTOPHAGY; EXPRESSION; MODULUS;

D O I：

10.7150/ijbs.64152

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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.

引用

页码：4140 / 4153

页数：14

共 49 条

[1] THE MODE OF ACTION OF A GLYCOSAMINOGLYCAN-PEPTIDE-COMPLEX (RUMALON) ON ARTICULAR-CARTILAGE OF THE RAT INVIVO [J].