ADAMTS4, also known as aggrecanase-1, is a member of the ADAMTS (a disintegrin and metalloproteinase with thrombospondin motifs) family. It is a crucial proteolytic enzyme involved in extracellular matrix (ECM) remodeling, as it can cleave various ECM components such as versican [2]. In addition, it has been associated with multiple biological processes and diseases, and genetic models like gene knockout (KO) mouse models are valuable for studying its functions.

In severe respiratory viral infections, damage-responsive lung fibroblasts secrete ADAMTS4, which, along with inflammatory cytokines, modifies the lung microenvironment, promoting immune cell infiltration at the expense of lung function, and ADAMTS4 levels in the lower respiratory tract are associated with the severity of influenza virus infection [1]. In the amnion, ADAMTS4 is essential for versican cleavage at parturition, and its enhanced activity can be induced by inflammatory factors, with intra-amniotic injection of ADAMTS4 in mice leading to preterm birth [2]. In oligodendrocyte differentiation, genetic ablation of Adamts4 in mice impedes NG2 proteolysis, leading to elevated PDGFRα signaling, impaired oligodendrocyte differentiation, and reduced axonal myelination and myelin repair [3]. In lung cancer, knockdown of ADAMTS4 inhibits cell proliferation, migration, and HUVECs tubule formation, while overexpression promotes these processes by stabilizing c-Myc and activating the MAPK signaling pathway [4].

In conclusion, ADAMTS4 plays a significant role in ECM remodeling, tissue development, and disease progression. Findings from KO mouse models have revealed its functions in various biological processes and disease conditions, such as respiratory infections, parturition, oligodendrocyte differentiation, and cancer. Understanding ADAMTS4 can potentially provide new therapeutic strategies for these diseases.