Igfbp3, or Insulin-like growth factor binding protein 3, is a multifunctional protein. It binds to IGF-1 and is involved in regulating growth, survival, and aging, with its actions also extending to apoptosis, cell proliferation, and differentiation [2,3]. It participates in multiple signaling pathways, such as the IGF-1 signaling pathway [3], and has significance in various biological processes including tooth development, endometrial remodeling, and cardiac fibroblast activation [1,4,5]. Genetic models, like gene knockout (KO) models, are valuable for studying Igfbp3's functions.

In a study using the Nuclease technology system to knockout the Igfbp3 gene in murine cells (B16F1), it was found that Igfbp3 KO cells had enhanced SA-β-gal staining and short telomere length, with higher expression levels of senescence-related proteins like PI3K, AKT1, PDK1, and p53, suggesting its key role in the aging mechanism [3]. In human endometrial mesenchymal stem cells, IGFBP3-knockout led to the cells losing stemness and differentiating towards the chondrogenic lineage [2]. In glioma, knockdown of Igfbp3 suppressed cell proliferation, induced cell cycle G2/M arrest and apoptosis, and delayed in vivo tumor growth in mouse models, indicating it as a potential therapeutic target [6].

In conclusion, Igfbp3 plays essential roles in multiple biological functions including aging, cell differentiation, and tumor growth regulation. The use of Igfbp3 KO mouse models has provided insights into its role in aging-related mechanisms and in diseases such as glioma, highlighting its potential as a therapeutic target in these disease areas.