Department of Orthopedic Surgery, Tongde Hospital of Zhejiang Province, Hangzhou, China.
Department of Ultrasound, The 903rd Hospital of PLA, Hangzhou, China.
PLoS One. 2024 Nov 22;19(11):e0313560. doi: 10.1371/journal.pone.0313560. eCollection 2024.
Osteoarthritis (OA) is a joint disease in which cartilage degradation is the hallmark pathological change. In this study, we investigated the anti-osteoarthritic effects of DHEA in rabbit chondrocytes. Polymerase chain reaction was performed to evaluate the expression of a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS)-4, ADAMTS-5, aggrecan and collagen type 2. In addition, ERK1/2 signaling pathway components were analyzed by Western blotting. In IL-1β-induced chondrocytes, the phosphorylation of ERK1/2 was enhanced, and the downstream catabolic genes, including ADAMTS-4 and ADAMTS-5, were upregulated, while the anabolic genes aggrecan and collagen type 2 were downregulated. DHEA administration restored the IL-1β-induced imbalance in anabolic and catabolic gene expression. In addition, the phosphorylation of ERK1/2 was suppressed by DHEA. Then, PD98059 was used to block the ERK1/2 signaling pathway. The protective effect of DHEA was significantly increased when ERK1/2 signaling was inactivated. DHEA may exert its protective effect by suppressing ADAMTS in an ERK1/2-dependent manner in rabbit chondrocytes.
骨关节炎（OA）是一种关节疾病，其特征性病理改变为软骨降解。在这项研究中，我们研究了脱氢表雄酮（DHEA）在兔软骨细胞中的抗骨关节炎作用。聚合酶链反应（PCR）用于评估解整合素和金属蛋白酶与凝血酶敏感蛋白 4（ADAMTS-4）、ADAMTS-5、聚集蛋白聚糖和 2 型胶原的表达。此外，通过 Western blot 分析 ERK1/2 信号通路成分。在 IL-1β诱导的软骨细胞中，ERK1/2 的磷酸化增强，下游分解代谢基因（包括 ADAMTS-4 和 ADAMTS-5）上调，而合成代谢基因聚集蛋白聚糖和 2 型胶原下调。DHEA 给药恢复了 IL-1β诱导的合成代谢和分解代谢基因表达失衡。此外，DHEA 抑制了 ERK1/2 的磷酸化。然后，使用 PD98059 阻断 ERK1/2 信号通路。当 ERK1/2 信号失活时，DHEA 的保护作用显著增加。DHEA 可能通过 ERK1/2 依赖性方式抑制 ADAMTS 发挥其保护作用在兔软骨细胞中。
