Dexamethasone causes calcium deposition and degeneration in human anterior cruciate ligament cells through endoplasmic reticulum stress

Abstract

BackgroundDexamethasone is widely used in the treatment of joint diseases due to its anti-inflammatory properties. However, it can cause serious adverse effects. The anterior cruciate ligament (ACL) is an important stabilizer of the knee joint. However, the effect of dexamethasone treatment on the ACL is unclear. ObjectiveThis study aims to explore the effects of dexamethasone on ACL tissues and cells through in vitro and in vivo experiments. ResultsIn vitro, we found that after treatment with dexamethasone, human ACL cell apoptosis was increased, type I collagen (COL1A1) content was decreased, mineralization related genes (ENPP1 and ANKH) and calcified nodules were increased, and endoplasmic reticulum stress (ERS) was enhanced. However, ERS inhibitors could significantly inhibit the increase in calcification and the decrease in COL1A1 induced by dexamethasone. In vivo, Wistar rats received the infra-articular injection with dexamethasone (0.5 mg/kg) for 8 weeks. We found that dexamethasone treatment decreased the COL1A1 content and increased the COL2A1 content in the ACL tissues of rats and that chondroid differentiation and mineralization occurred. Meanwhile, the expression of ERS-related proteins was increased. ConclusionDexamethasone increased the calcification of ACL cells and caused ACL degeneration through ERS, suggesting that long-term treatment with dexamethasone may cause adverse effects on ACL tissue and increase the risk of long-term rupture.