Figure 6.

Model of the signalling pathways modulated by Mdk and the effect of Mdk‐Ab treatment on osteoblasts and chondrocytes. (A) The circulating Mdk protein may bind to a receptor complex of LRP‐6 and PTPRz, decreasing LRP‐6 phosphorylation and leading to stabilization of the β‐catenin degradation complex. Wnt/β‐catenin signalling is decreased in the presence of Mdk. (B) Mdk‐Ab treatment abolishes the interaction of Mdk with its receptor complex, leading to increased translocation of β‐catenin to the cell nucleus and increased Wnt/β‐catenin signalling in osteoblasts. (C) Locally expressed Mdk may act positively on Wnt/β‐catenin signalling in chondrocytes via intracrine signalling after binding to LRP‐1 and nucleolin. In this model, Mdk‐Ab treatment would not have an effect on chondrocytes. APC, adenomatous polyposis coli; GSK‐3b, glycogen synthase kinase‐3b; TCF/LEF, T cell factor/lymphoid enhancer factor.