Department of Microbiology, Anatomy, Physiology and Pharmacology, La Trobe University, Melbourne, VIC 3086, Australia.
Department of Infectious Diseases, St Vincent's Hospital, Melbourne, VIC 3065, Australia.
Genes (Basel). 2022 Nov 25;13(12):2210. doi: 10.3390/genes13122210.
Fluoroquinolone antibiotics are associated with increased risk of tendinopathy and tendon rupture, which can occur well after cessation of treatment. We have previously reported that the fluoroquinolone ciprofloxacin (CPX) reduced proteoglycan synthesis in equine tendon explants. This study aimed to determine the effects of CPX on proteoglycan catabolism and whether any observed effects are reversible. Equine superficial digital flexor tendon explant cultures were treated for 4 days with 1, 10, 100 or 300 µg/mL CPX followed by 8 days without CPX. The loss of [S]-labelled proteoglycans and chemical pool of aggrecan and versican was studied as well as the gene expression levels of matrix-degrading enzymes responsible for proteoglycan catabolism. CPX suppressed [S]-labelled proteoglycan and total aggrecan loss from the explants, although not in a dose-dependent manner, which coincided with downregulation of RNA expression of MMP-9, -13, ADAMTS-4, -5. The suppressed loss of proteoglycans was reversed upon removal of the fluoroquinolone with concurrent recovery of MMP and ADAMTS RNA expression, and downregulated TIMP-2 and upregulated TIMP-1 expression. No changes in MMP-3 expression by CPX was observed at any stage. These findings suggest that CPX suppresses proteoglycan catabolism in tendon, and this is partially attributable to downregulation of matrix-degrading enzymes.
氟喹诺酮类抗生素与腱病和肌腱断裂的风险增加有关，这种风险在治疗停止后很久仍可能发生。我们之前曾报道过氟喹诺酮类药物环丙沙星（CPX）可降低马肌腱外植体中的蛋白聚糖合成。本研究旨在确定 CPX 对蛋白聚糖分解代谢的影响，以及是否观察到任何可逆转的影响。用 1、10、100 或 300μg/ml CPX 处理马的浅层指屈肌腱外植体培养物 4 天，然后不使用 CPX 培养 8 天。研究了[S]-标记蛋白聚糖的丢失和聚集蛋白聚糖和 versican 的化学库，以及负责蛋白聚糖分解代谢的基质降解酶的基因表达水平。CPX 抑制了外植体中[S]-标记蛋白聚糖和总聚集蛋白聚糖的丢失，但不是剂量依赖性的，这与 MMP-9、-13、ADAMTS-4、-5 的 RNA 表达下调一致。去除氟喹诺酮类药物后，蛋白聚糖的丢失得到了抑制，同时 MMP 和 ADAMTS RNA 表达恢复，TIMP-2 下调，TIMP-1 上调。CPX 对 MMP-3 的表达没有任何变化。这些发现表明 CPX 抑制肌腱中蛋白聚糖的分解代谢，这部分归因于基质降解酶的下调。
