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J Cell Sci. 2013 Apr 1;126(Pt 7):1650-8. doi: 10.1242/jcs.119859. Epub 2013 Feb 19.

WISP3-IGF1 interaction regulates chondrocyte hypertrophy.

Author information

1
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.

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.

KEYWORDS:

Hypertrophy; IGF1; WISP3

PMID:
23424195
DOI:
10.1242/jcs.119859
[Indexed for MEDLINE]
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