Department of Orthopedic Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, 324 Jingwuweiqi Road, Jinan, 250021, Shandong, China.
Biology Institute, Qilu University of Technology (Shandong Academy of Sciences), 28789 East Jingshi Road, Jinan, 250103, Shandong, China.
J Orthop Surg Res. 2024 Nov 4;19(1):718. doi: 10.1186/s13018-024-05202-z.
The aim of this study was to investigate the therapeutic effects and mechanisms of PRP-exos combined with cyclic peptide-modified β-TCP scaffold in the treatment of rabbit knee cartilage defect.
PRP-exos were extracted and characterized by TEM, NTA and WB. The therapeutic effects were evaluated by ICRS score, HE staining, Immunohistochemistry, qRT-PCR and ELISA. The repair mechanism of PRP-exos was estimated and predicted by miRNA sequencing analysis and protein-protein interaction network analysis.
The results showed that PRP-exos had a reasonable size distribution and exhibited typical exosome morphology. The combination of PRP-exos and cyclic peptide-modified β-TCP scaffold improved ICRS score and the expression level of COL-2, RUNX2, and SOX9. Moreover, this combination therapy reduced the level of MMP-3, TNF-α, IL-1β, and IL-6, while increasing the level of TIMP-1. In PRP-exos miRNA sequencing analysis, the total number of known miRNAs aligned across all samples was 252, and a total of 91 differentially expressed miRNAs were detected. The results of KEGG enrichment analysis and the protein-protein interaction network analysis indicated that the PI3K/AKT signaling pathway could impact the function of chondrocytes by regulating key transcription factors to repair cartilage defect.
PRP-exos combined with cyclic peptide-modified β-TCP scaffold effectively promoted cartilage repair and improved chondrocyte function in rabbit knee cartilage defect. Based on the analysis and prediction of PRP-exos miRNAs sequencing, PI3K/AKT signaling pathway may contribute to the therapeutic effect. These findings provide experimental evidence for the application of PRP-exos in the treatment of cartilage defect.
本研究旨在探讨 PRP-exos 联合环肽修饰的β-TCP 支架在兔膝关节软骨缺损治疗中的疗效及机制。
采用 TEM、NTA 和 WB 对 PRP-exos 进行提取和鉴定。采用 ICRS 评分、HE 染色、免疫组化、qRT-PCR 和 ELISA 评价疗效。通过 miRNA 测序分析和蛋白质相互作用网络分析预测和评估 PRP-exos 的修复机制。
结果表明，PRP-exos 具有合理的粒径分布，呈现典型的外泌体形态。PRP-exos 与环肽修饰的β-TCP 支架联合应用可提高 ICRS 评分及 COL-2、RUNX2 和 SOX9 的表达水平。此外，这种联合治疗还降低了 MMP-3、TNF-α、IL-1β 和 IL-6 的水平，同时增加了 TIMP-1 的水平。在 PRP-exos miRNA 测序分析中，所有样本中匹配的已知 miRNA 总数为 252 个，共检测到 91 个差异表达 miRNA。KEGG 富集分析和蛋白质相互作用网络分析的结果表明，PI3K/AKT 信号通路可通过调节关键转录因子来修复软骨缺损，从而影响软骨细胞的功能。
PRP-exos 联合环肽修饰的β-TCP 支架可有效促进兔膝关节软骨缺损的软骨修复，改善软骨细胞功能。基于 PRP-exos miRNA 测序的分析和预测，PI3K/AKT 信号通路可能有助于其治疗效果。这些发现为 PRP-exos 在软骨缺损治疗中的应用提供了实验依据。
