title: WISP3-IGF1 interaction regulates chondrocyte hypertrophy.
abstract: 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 insulin-like growth factor 1 (IGF1) and inhibits IGF1 secretion. Additionally, WISP3 curbs IGF1-mediated collagen X expression, accumulation of reactive oxygen species (ROS) and alkaline phosphatase activity, all of which are associated with the induction of chondrocyte hypertrophy. Interestingly, both IGF1 and ROS in turn trigger an increase in WISP3 expression. Together, our 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.
authors: Cancer Biology and Inflammatory Disorder Division, Council of Scientific and Industrial Research - Indian Institute of Chemical Biology, 4 Raja S.C. Mullick Road, Kolkata 700 032, India.
authors: Srinivasa Rao
authors: SR
authors: Repudi
authors: Milan
authors: M
authors: Patra
authors: Malini
authors: M
authors: Sen
mesh_terms: D055511:CCN Intercellular Signaling Proteins / Q000378:metabolism*; D049108:Cell Enlargement; D002460:Cell Line; D019902:Chondrocytes / Q000166:cytology* / Q000378:metabolism*; D006801:Humans; D015151:Immunoblotting; D047468:Immunoprecipitation; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D011485:Protein Binding; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D055511:CCN Intercellular Signaling Proteins; C400081:CCN6 protein, human; D017382:Reactive Oxygen Species; D007334:Insulin-Like Growth Factor I
keywords: Hypertrophy; IGF1; WISP3