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.
Böhm
Beate B
BB
Division of Rheumatology, Johann Wolfgang Goethe University, Frankfurt am Main, Germany.
Schirner
Andrea
A
Friedrich-Alexander-University of Erlangen-Nuremberg, Erlangen, Germany.
Burkhardt
Harald
H
Division of Rheumatology, Johann Wolfgang Goethe University, Frankfurt am Main, Germany.
D051722:ADAM Proteins / Q000235:genetics / Q000502:physiology*; D001483:Base Sequence; D015153:Blotting, Western; D002460:Cell Line; D019902:Chondrocytes / Q000166:cytology / Q000378:metabolism*; D017931:DNA Primers; D005109:Extracellular Matrix / Q000378:metabolism*; D006801:Humans; D047468:Immunoprecipitation; D008565:Membrane Proteins / Q000235:genetics / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology*
D017931:DNA Primers; D008565:Membrane Proteins; D051722:ADAM Proteins; C098660:ADAM15 protein, human
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