Wnt3a, a member of the Wnt family, is a secreted glycoprotein. It plays key roles in regulating pleiotropic cellular functions, such as self-renewal, proliferation, differentiation, and motility, mainly through the canonical Wnt/β-catenin signaling pathway. This pathway is crucial in many biological processes, including development and disease [3].

In various disease contexts, studies have explored Wnt3a's role. In chronic obstructive pulmonary disease (COPD), compromised Wnt/β-catenin signaling-related regeneration led to disease progression. Engineered extracellular vesicles (EVs) delivering Wnt3a (Wnt3aWG EVs) could activate Wnt signaling, promote cell growth after human alveolar epithelial cell injury, and restore impaired pulmonary function in an elastase-induced emphysema model [1]. In colorectal cancer (CRC), Wnt3a is associated with angiogenesis and CRC progression, making it a potential target [2]. In cartilage repair, WNT3a-loaded exosomes could penetrate cartilage, activate WNT signaling, and improve the repair of osteochondral defects in mice, while recombinant WNT3a failed to do so [4]. In hepatocellular carcinoma (HCC), Wnt3a overexpression was associated with rat hepatocarcinogenesis, and it could potentially be a biomarker for early HCC monitoring [5].

In conclusion, Wnt3a is essential in regulating multiple cellular functions through the canonical Wnt/β-catenin pathway. Research using in vivo models, like the elastase-induced emphysema model, mouse models with osteochondral defects, and rat models of hepatocarcinogenesis, has revealed its significance in diseases such as COPD, cartilage-related disorders, and HCC. These findings suggest that targeting Wnt3a could be a promising therapeutic strategy for these diseases.