Liao Qing, Chen Jun, Liu Gang
School of Traditional Chinese Medicine, Southern Medical University, Guangzhou, 510000, China.
Department of Rehabilitation Medicine, Nanfang Hospital of Southern Medical University, Guangzhou, 510000, China.
Sci Rep. 2025 Mar 20;15(1):9644. doi: 10.1038/s41598-025-92413-x.
Previous studies have reported that low-intensity pulsed ultrasound (LIPUS) can alleviate cartilage degradation in osteoarthritis (OA). However, the functions and mechanisms of LIPUS in synovial fibrosis with OA require further study. To investigate the role of the PI3K/AKT signaling pathway in synovial fibrosis and in LIPUS treatment in synovial fibrosis, a TGF-β stimulated rat FLS cell model and a rat OA animal model based on anterior cruciate ligament transection (ACLT) and partial medial meniscectomy (MMx) were used. The results revealed that LIPUS delayed the progression of OA. Masson staining revealed that LIPUS reduced the collagen deposition of synovial tissue in OA rats. Correspondingly, immunofluorescence demonstrated that LIPUS significantly downregulated the expression of α-SMA, Col1a1 and Col3a1 in OA rats. Moreover, TGF-β stimulation upregulated fibrosis markers at the mRNA and protein levels in FLS, as well as increased phosphorylation-dependent activation of the PI3K/Akt pathway. 740Y-P was found to promote the fibrotic change of FLS induced by TGF-β, but LY294002 reduced its expression. However, LIPUS inhibits the fibrotic change and activation of the PI3K/Akt pathway in FLS under stimulation of TGF-β. In conclusion, LIPUS alleviates synovial fibrosis by blocking the PI3K/AKT pathway.
先前的研究报道，低强度脉冲超声（LIPUS）可减轻骨关节炎（OA）中的软骨降解。然而，LIPUS在OA滑膜纤维化中的作用和机制尚需进一步研究。为了探究PI3K/AKT信号通路在滑膜纤维化及LIPUS治疗滑膜纤维化中的作用，使用了转化生长因子-β（TGF-β）刺激的大鼠成纤维样滑膜细胞（FLS）模型以及基于前交叉韧带横断（ACLT）和部分内侧半月板切除术（MMx）的大鼠OA动物模型。结果显示，LIPUS延缓了OA的进展。Masson染色显示，LIPUS减少了OA大鼠滑膜组织中的胶原沉积。相应地，免疫荧光表明，LIPUS显著下调了OA大鼠中α-SMA、Col1a1和Col3a1的表达。此外，TGF-β刺激上调了FLS中纤维化标志物的mRNA和蛋白水平，同时增加了PI3K/Akt途径的磷酸化依赖性激活。发现740Y-P可促进TGF-β诱导的FLS纤维化改变，但LY294002可降低其表达。然而，LIPUS在TGF-β刺激下抑制了FLS中的纤维化改变及PI3K/Akt途径的激活。总之，LIPUS通过阻断PI3K/AKT途径减轻滑膜纤维化。
