Department of Orthopaedic Surgery, Qilu Hospital of Shandong University, Jinan, China.
Eur Rev Med Pharmacol Sci. 2018 Apr;22(7):2119-2125. doi: 10.26355/eurrev_201804_14745.
To explore the effect and mechanism of precartilaginous stem cells (PSCs) engraftment-inducing tissue repair in a knee osteoarthritis (OA) rat model.
Knee osteoarthritis (OA) model was constructed in Sprague Dawley (SD) rats by partial removal of the medial meniscus of the right knee. PSCs were engrafted by injecting precartilaginous stem cells (PSCs) into the right knee cavity. At 4 and 8 weeks after model construction, the serum levels of interleukine (IL)-1β, tumor necrosis factor (TNF)-α, and IL-6 were assessed using enzyme-linked immunosorbent assay (ELISA). Hematoxylin-eosin (HE) staining was performed to assess the histopathology of synovial membrane and cartilage. Western blot analysis was used to assess Notch1, Bcl-2 and Bax levels in the articular cartilage.
At 4 and 8 weeks, OA rats demonstrated significantly higher IL-1β, TNF-α, and IL-6 levels than normal rats (p < 0.05), whereas PSCs treatment prominently attenuated IL-1β upregulation (p < 0.05). In OA rats, the number of chondrocytes dramatically decreased over time in OA rats, with disruption of chondrocytes organization and cell layers. PSCs alleviated the deterioration of cartilage, as evidenced by the relatively smooth articular surface, distinct tidemark and clear cell layers. The model and treatment groups demonstrated substantially higher Notch1 expression. The Bcl-2/Bax value in the OA rats was lower than the control group, while PSCs treatment led to increase in Bcl-2/Bax value.
PSCs treatment downregulated the expression of inflammatory cytokines, alleviating osteoarthritis in the knee of rats. Notch1 signaling pathway plays an important role in this ameliorating effect of PSCs treatment.
探讨诱导组织修复的软骨前体细胞（PSCs）移植在膝骨关节炎（OA）大鼠模型中的作用和机制。
通过切除右侧膝关节内侧半月板构建膝骨关节炎（OA）模型。将软骨前体细胞（PSCs）注入右侧膝关节腔，进行 PSCs 移植。在模型构建后 4 周和 8 周，通过酶联免疫吸附试验（ELISA）评估血清中白细胞介素（IL）-1β、肿瘤坏死因子（TNF）-α和 IL-6 的水平。通过苏木精-伊红（HE）染色评估滑膜和软骨的组织病理学。通过 Western blot 分析评估关节软骨中的 Notch1、Bcl-2 和 Bax 水平。
在 4 周和 8 周时，OA 大鼠的血清 IL-1β、TNF-α和 IL-6 水平明显高于正常大鼠（p<0.05），而 PSCs 治疗明显降低了 IL-1β的上调（p<0.05）。在 OA 大鼠中，随时间推移，软骨细胞数量显著减少，软骨细胞结构和细胞层紊乱。PSCs 缓解了软骨的恶化，表现为关节表面相对光滑，清晰的软骨层和清晰的软骨层。模型组和治疗组 Notch1 表达明显升高。OA 大鼠的 Bcl-2/Bax 值低于对照组，而 PSCs 治疗导致 Bcl-2/Bax 值升高。
PSCs 治疗可下调炎症细胞因子的表达，缓解大鼠膝关节的骨关节炎。Notch1 信号通路在 PSCs 治疗的这种改善作用中起重要作用。
