Amelogenins: Multifaceted Proteins for Dental and Bone Formation and Repair

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Signaling Effect of Leucine-Rich Amelogenin Peptide (Lrap) on Bone Regeneration

Pp. 208-213 (6)

Yan Zhou, Christina. J. Newcomb, Rungnapa Warotayanont, Malcolm L. Snead and S. I. Stupp

Abstract

Amelogenin is the most abundant protein of the enamel organic matrix and is a structural protein indispensable for enamel formation. A commercial product Emdogain, consisting largely of alternatively spliced and processed amelogenins, could induce new bone, cementum and periodontal ligament formation in the jaws. Using mouse embryonic stem (ES) cells as a model system, we demonstrate that one of the amelogenin splicing isoforms, Leucine-rich Amelogenin Peptide (LRAP) activates the canonical Wnt signaling pathway to induce osteogenic differentiation of mouse ES cells through the concerted regulation of Wnt agonists and antagonists. Furthermore, LRAP stimulates bone regeneration in a rat femoral critical size defect model.

Keywords:

LRAP, Leucine-rich Amelogenin Peptide, Wnt Signaling Pathway, ES Cell, Osteogenic Differentiation, Osteogenesis, Bone Regeneration

Affiliation:

The Center for Craniofacial Molecular Biology, University of Southern California, Los Angeles CA.