Xin Deng, Junwen Zheng, Jiacheng Zou, Qiongyu Xun, Huanzong He, Peng Li, Juan Liao
Department of Stomatology, The Affiliated Stomatological Hospital, Southwest Medical University, Luzhou, Sichuan, China.
School of Medicine, University of Electronic Science and Technology of China, Chengdu, Sichuan, China.
Regen Ther. 2025 Apr 26;29:474-483. doi: 10.1016/j.reth.2025.04.013. eCollection 2025 Jun.
Concentrated growth factor (CGF) is widely applied in clinical practice, but whether it has bone promoting effects and its mechanism of action are still the focus of discussion. In this study, in vitro experiments demonstrate that CGF can promote the expression of Arg-1 in BMDM cells, facilitating their polarization towards the M2 macrophages and encouraging the secretion of IL-10 and VEGF-A. CGF modulates M1 macrophages by reducing the expression of iNOS, while enhancing Arg-1 expression, thereby converting them to M2 macrophages. This is accompanied by a decrease in the secretion of TNF- and IL-1β, and an increase in the secretion of IL-10 and VEGF-A. Mechanistically, CGF promotes the phosphorylation of STAT3, which in turn induces M2 macrophage polarization, suggesting that the function of CGF-mediated macrophages may be associated with the STAT3 signaling pathway. Moreover, CGF-mediated macrophages were found to enhance osteoblast activity, increasing the expression of ALP, RUNX2, and BMP-2, and improving cell migration capabilities. In vivo experiments showed that CGF could early recruit M2 macrophages to the bone defect site, promoting the expression of bone formation-related proteins such as ALP and BMP-2, and accelerating bone tissue regeneration. In summary, our study demonstrates that CGF can induce bone repair and regeneration by promoting immune modulation and macrophage polarization.
浓缩生长因子（CGF）在临床实践中广泛应用，但其是否具有促进骨生成的作用及其作用机制仍是讨论的焦点。在本研究中，体外实验表明，CGF可促进骨髓来源巨噬细胞（BMDM）中精氨酸酶-1（Arg-1）的表达，促使其向M2巨噬细胞极化，并促进白细胞介素-10（IL-10）和血管内皮生长因子-A（VEGF-A）的分泌。CGF通过降低诱导型一氧化氮合酶（iNOS）的表达来调节M1巨噬细胞，同时增强Arg-1的表达，从而将它们转化为M2巨噬细胞。这伴随着肿瘤坏死因子-α（TNF-α）和白细胞介素-1β（IL-1β）分泌的减少，以及IL-10和VEGF-A分泌的增加。机制上，CGF促进信号转导和转录激活因子3（STAT3）的磷酸化，进而诱导M2巨噬细胞极化，提示CGF介导的巨噬细胞功能可能与STAT3信号通路有关。此外，发现CGF介导的巨噬细胞可增强成骨细胞活性，增加碱性磷酸酶（ALP）、 runt相关转录因子2（RUNX2）和骨形态发生蛋白-2（BMP-2）的表达，并提高细胞迁移能力。体内实验表明CGF可早期将M2巨噬细胞募集到骨缺损部位，促进ALP和BMP-2等骨形成相关蛋白的表达，并加速骨组织再生。总之，我们的研究表明CGF可通过促进免疫调节和巨噬细胞极化来诱导骨修复和再生。
