ADAM15 modulates outside-in signalling in chondrocyte–matrix interactions

  • ADAM15 belongs to a family of transmembrane multi-domain proteins implicated in proteolysis, cell–cell and cell–matrix interactions in various disease conditions. In osteoarthritis (OA), ADAM15 is up-regulated in the chondrocytes already at early stages of cartilage degeneration where it seems to exert homeostatic effects likely associated with its ability to enhance integrin-mediated chondrocyte adhesion to the surrounding collagen matrix. The aim of our present study was, therefore, to characterize functional domains of ADAM15 involved in collagen II (CII) interaction and to analyse associated outside-in signalling events. Accordingly, ADAM15 and respective deletion mutants were stably transfected into the chondrocyte cell line T/C28a4. Transfected cells were adhered to CII and phosphoproteins analysed by Western blotting. Co-immunoprecipitation served to identify protein binding to ADAM15. Our results elucidate the prodomain as critical for the capacity of ADAM15 to enhance CII adhesion, thereby identifying for the first time a cell-adhesive role of a metalloproteinase prodomain. Moreover, the cytoplasmic tail of ADAM15 confers a modulatory effect on the autophosphorylation site Y397 of the focal adhesion kinase (FAK) during chondrocyte–collagen interaction. In conclusion, the newly uncovered impact of ADAM15 on signalling events that arise from chondrocyte interactions with its collagen matrix might contribute to the elucidation of the mechanism underlying its proposed chondroprotective role in degenerative cartilage disease.

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Author:Beate B. BöhmORCiD, Andrea Schirner, Harald BurkhardtORCiDGND
Pubmed Id:
Parent Title (English):Journal of cellular and molecular medicine
Place of publication:Hoboken, NJ
Document Type:Article
Date of Publication (online):2008/09/04
Date of first Publication:2008/09/04
Publishing Institution:Universitätsbibliothek Johann Christian Senckenberg
Release Date:2013/02/08
Tag:ADAM15; chondrocyte; collagen adhesion; focal adhesion kinase; osteoarthritis
Page Number:11
First Page:2634
Last Page:2644
© 2008 The Authors Journal compilation © 2009 Foundation for Cellular and Molecular Medicine/Blackwell Publishing Ltd. This is an Open Access article under the terms of the Creative Commons Attribution Non Commercial License which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.
Institutes:Medizin / Medizin
Dewey Decimal Classification:6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
Licence (German):License LogoCreative Commons - Namensnennung-Nicht kommerziell 3.0