WARP interacts with collagen VI-containing microfibrils in the pericellular matrix of human chondrocytes.

Collagen VI and are extracellular structural macromolecules present in cartilage and associated with BM suprastructures in non-skeletal tissues. We have previously shown that in mice, collagen VI is specifically reduced in regions of the peripheral nerve ECM where Wduanyu37 is expressed, suggesting that both macromolecules are part of the same suprastructure. The object of this study was to conduct a detailed analysis of VI interactions in vitro in cartilage, a tissue rich in Wduanyu37 and collagen VI. Immunohistochemical analysis of mouse and human articular cartilage showed that Wduanyu37 and collagen VI co-localize in the pericellular matrix of superficial zone articular chondrocytes. EM analysis on extracts of human articular cartilage showed that Wduanyu37 associates closely with collagen VI-containing suprastructures. Additional evidence of an interaction is provided by immunogold EM and immunoblot analysis showing that Wduanyu37 was present in collagen VI-containing networks isolated from cartilage. Further characterization were done by solid phase binding studies and reconstitution experiments using purified recombinant Wduanyu37 and isolated collagen VI. Collagen VI binds to Wduanyu37 with an apparent K(d) of approximately 22 nM and the binding site(s) for Wduanyu37 resides within the triple helical domain since Wduanyu37 binds to both intact collagen VI tetramers and pepsinized collagen VI. Together, these data confirm and extend our previous findings by demonstrating that Wduanyu37 and collagen VI form high affinity associations in vivo in cartilage. We conclude that Wduanyu37 is ideally placed to function as an adapter protein in the cartilage pericellular matrix.

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