Wnt3a, a member of the wingless-type MMTV integration site family, is a secreted glycoprotein. It plays key roles in regulating multiple cellular functions such as self-renewal, proliferation, differentiation, and motility, mainly through the canonical Wnt/β-catenin signaling pathway [3]. This pathway is crucial in various biological processes during development and in maintaining tissue homeostasis.

In lung injury, Wnt3a-loaded extracellular vesicles (EVs) can promote alveolar epithelial regeneration. The engineered Wnt3aWG EVs activate Wnt signaling and cell growth after human alveolar epithelial cell injury, and restore impaired pulmonary function and enlarged airspace in an elastase-induced emphysema model [1]. In colorectal cancer, Wnt3a is associated with angiogenesis and disease progression, making it a potential therapeutic target [2]. Wnt3a can either promote or suppress tumor progression depending on the cancer type. For example, in hepatocellular carcinoma, its overexpression is associated with carcinogenesis and it may be a biomarker for early-stage monitoring [6]. In cartilage, Wnt3a-loaded exosomes can contribute to the repair of osteochondral defects, while knockdown of Wnt3a in rat chondrocytes promotes collagen type II expression, which is important for cartilage homeostasis and a potential therapy for osteoarthritis [4,5].

In conclusion, Wnt3a is essential in regulating diverse cellular functions through the canonical Wnt/β-catenin pathway. Studies using models like Wnt3a-loaded EVs or knockdown in cells have revealed its roles in diseases such as lung injury, cancer, and osteoarthritis. These findings contribute to understanding disease mechanisms and developing potential therapeutic strategies.