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Role of WISP3 (Wnt Induced Secreted Protein 3) in Cartilage Maintenance

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Field Value
 
Title Role of WISP3 (Wnt Induced Secreted Protein 3) in
Cartilage Maintenance
 
Creator Srinivasarao, R
 
Subject Drug Development/Diagnostics & Biotechnology
 
Description WISP3 (Wnt induced secreted protein 3) is a multi domain protein which is expressed mostly in cells of mesenchymal origin and in breast epithelial cells. WISP3 shares a similar modular structure with existing CCN family proteins Cyr 61, CTGF and NOV along with WISP1 and WISP2. Mutations in the WISP3 gene are associated with progressive pseudorheumatoid dysplasia(PPRD), an autosomal recessive skeletal disorder manifested in children at 3-8 years of age.Progressive cartilage loss in between articular bone joints and vertebra is one of the important
prognostic factors in patients with PPRD. There is experimental evidence suggesting that WISP3 promotes the expression of extra cellular cartilage specific matrix proteins such as collagen II and aggrecan. Contemporary literature also suggests that WISP3 may be involved in regulating the accumulation of reactive oxygen species, which could otherwise damage cartilage integrity.
WISP3 has a putative IGF binding protein domain, but the precise mechanism by which WISP3 modulates IGF1 functions with respect to cartilage homeostasis is not known. My experimental results suggest that WISP3 interacts with IGF1 and inhibits IGF1 secretion. In addition, WISP3
reduces IGF1 induced collagen X expression and alkaline phosphatase activity most likely through
modulating signaling events that promote RUNX2 transcription factor activation. Furthermore,
WISP3 curbs the IGF1 induced accumulation of ROS, which in turn potentiates WISP3 expression. My findings thus indicate that WISP3 is a potent regulator of chondrocyte
hypertrophy. It is quite possible that PPRD patients suffer from cartilage loss at least partly on account of uncontrolled chondrocyte hypertrophy in the absence of an appropriately functional WISP3 protein and thus strengthen the existing data featuring WISP3 being important for the
maintenance of chondrocyte / cartilage differentiation.
 
Date 2013
 
Type Thesis
NonPeerReviewed
 
Format application/pdf
 
Identifier http://www.eprints.iicb.res.in/1941/1/SRINIVASARAO_R__SOFT.pdf
Srinivasarao, R (2013) Role of WISP3 (Wnt Induced Secreted Protein 3) in Cartilage Maintenance. PhD thesis, Calcutta University.
 
Relation http://www.eprints.iicb.res.in/1941/