Department of Rheumatology Immunology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, China.
Eur Rev Med Pharmacol Sci. 2020 Dec;24(24):12938-12947. doi: 10.26355/eurrev_202012_24197.
Abnormal lipid metabolism plays a role that cannot be ignored in articular cartilage bone marrow lesions, synovial inflammation, and the destruction of chondrocytes (CHs). Ceramide is one of the key constructions of membrane lipid bilayers, which is an intracellular lipid mediator regulating varieties of cellular behaviors. The purpose of this study was to explore the role of ceramide and its inhibitor in the development of the CHs degeneration.
CHs were isolated from the cartilage collecting from the osteoarthritis (OA) patients, and oleic acid/palmitic (O/P) acid was used to induce CHs lipid disordered. Then, myriocin was used to inhibit the accumulation of ceramide. After that, the apoptosis, cell viability, glucose uptake, oxidative stress, and the chondrogenic gene expression were tested to evaluate the degenerated degree of CHs.
Results revealed that O/P induced CH apoptosis, ceramide accumulation, a higher level of oxidative stress, IL-1β and MMP-13, but it also decreased the collagen-Ⅱ and SOX-9 expressions and affected the glucose uptake of CHs. After the stimulation of myriocin, the side effects induced by O/P was partly reversed.
O/P induces the accumulation of ceramide and the degeneration of CHs, and myriocin can reject the harmful effect caused by O/P via the suppression of ceramide.
脂质代谢异常在关节软骨骨髓病变、滑膜炎症和软骨细胞(CHs)破坏中起着不可忽视的作用。神经酰胺是膜脂双层的关键结构之一,是一种调节多种细胞行为的细胞内脂质介质。本研究旨在探讨神经酰胺及其抑制剂在 CHs 退变中的作用。
从骨关节炎(OA)患者的软骨中分离 CHs,并用油酸/棕榈酸(O/P)酸诱导 CHs 脂质紊乱。然后,使用霉菌素来抑制神经酰胺的积累。之后,通过检测细胞凋亡、细胞活力、葡萄糖摄取、氧化应激和软骨形成基因表达来评估 CHs 的退变程度。
结果表明,O/P 诱导 CHs 凋亡、神经酰胺积累、更高水平的氧化应激、IL-1β和 MMP-13,但也降低了胶原-Ⅱ和 SOX-9 的表达,并影响 CHs 的葡萄糖摄取。在霉菌素的刺激下,O/P 诱导的副作用部分得到逆转。
O/P 诱导神经酰胺积累和 CHs 退变,霉菌素通过抑制神经酰胺来拒绝 O/P 引起的有害作用。