Abstract
Amelogenin is a major protein component of the enamel matrix associated with the progression of enamel mineralization. While the majority of research into amelogenin function has understandably focused on its role in enamel structure formation, recent work investigated the function of amelogenin as a signaling molecule. The present study examined whether amelogenin activates the Wnt/β -catenin signaling pathway in mouse calvarial osteoblasts and human periodontal ligament (PDL) cells and used the T 7 phage-display osteoblast library to identify a target protein with which amelogenin can interact. We found that amelogenin activates the Wnt/β -catenin signaling to induce osteogenic differentiation of osteoblasts and PDL cells. The DNA sequence that demonstrated one of the highest affinities for amelogenin was the tissue inhibitor of metalloproteinase-2 (TIMP-2). The physiological significance of the interaction between amelogenin and TIMP-2 is that amelogenin inhibits the effect of the TIMP-2 inhibitor on MMP activity. Amelogenin disrupted the TIMP-2 inhibitory effect and activated MMP. This increased MMP activity which facilitated the ability of osteoblasts to form a greater number of mineralized nodules. These findings suggest that amelogenin can induce cell differentiation of osteogenic cells through activation of the signaling pathway and may facilitate the mineralization procedure during matrix formation by increasing the MMP activities.
