WISP3 (Wnt Induced Secreted Protein 3) is a multi-domain protein of mesenchymal origin. Mutations in several domains of WISP3 cause PPRD (Progressive Pseudo Rheumatoid Dysplasia), which is associated with cartilage loss and restricted skeletal development. Despite several studies focusing on the functional characterization of WISP3, the molecular details underlying the course of PPRD remain unresolved. We are interested in analyzing the function of WISP3 in the context of cartilage integrity. The current study demonstrates that WISP3 binds to IGF1 and inhibits IGF1 secretion. Additionally, WISP3 curbs IGF1 mediated collagen X expression, ROS accumulation and alkaline phosphatase activity, all of which are associated with the induction of chondrocyte hypertrophy. Interestingly, both IGF1 and ROS in turn trigger increase in WISP3 expression. Altogether, our experimental results are indicative of an operational WISP3-IGF1 regulatory loop whereby WISP3 preserves cartilage integrity by restricting IGF1 mediated hypertrophic changes in chondrocytes, at least partly, upon interaction with IGF1.