Wnt16 is a member of the Wnt family of secreted cysteine-rich glycoproteins. It is involved in joint development, skeletal homeostasis, and has been linked to the occurrence of osteoarthritis. Wnt16 is also associated with pathways related to bone mass regulation, and its study has been facilitated by genetic models such as KO/CKO mouse models [1,3,4].

In KO mouse models, Wnt16 deficiency has been shown to cause postnatal bone loss and reduce systolic blood pressure. It also leads to abnormal vascular smooth muscle (VSM) mitochondrial morphology, reduced VSM contraction, and decreased expression of contractile genes, suggesting its role in cardiovascular physiology and VSM contractile phenotype, mediated via Taz signaling [2]. In Col2a1-Wnt16 transgenic mice and Wnt16fl/fl;Col2a1-Cre (Wnt16-cKO) mice, Wnt16 overexpression in chondrocytes inhibited chondrocyte hypertrophy during skeletal development, while Wnt16 deficiency exaggerated osteoarthritis (OA) progression, indicating its role in OA pathophysiology [4].

In conclusion, Wnt16 is essential for maintaining bone mass, regulating cardiovascular physiology, and influencing chondrocyte hypertrophy. Mouse KO/CKO models have been crucial in revealing its role in skeletal diseases and OA, highlighting its potential as a therapeutic target for these conditions.