Secreted Frizzled-related protein 3 (sFRP3)-mediated suppression of Interleukin-6 receptor release by A disintegrin and Metalloprotease 17 (ADAM17) is abrogated in the osteoarthritis-associated rare double variant of sFRP3

This study demonstrates a novel function of sFRP3 in suppression of the enzymatic activity of ADAM17 which results in the inhibition of ADAM17-meditated interleukin-6 receptor (IL-6R) shedding. By contrast, the rare double variant of sFRP3 failed to suppress ADAM17. The shed soluble IL-6R is linked to inflammation, cartilage degeneration, and osteolysis. Accordingly, enhanced activity of ADAM17 in cartilage, caused by the expression of the rare double sFRP3 variant, provides an explanation for the genetic effect of sFRP3 variants in joint disease. The finding that sFRP3 interacts with the ADAM17 substrate IL-6R also suggests a new regulatory mechanism by which the substrate is protected against shedding.

Source: BJ Cell - April 7, 2015 Category: Biochemistry Authors: M Oldefest, S Düsterhöft, C Desel, S Thysen, C Fink, B Rabe, R Lories, J Grötzinger, I Lorenzen Tags: BJ Cell Source Type: research