Glucose-Regulated Protein 78: A Novel Therapeutic Target for Amelogenin- Induced Periodontal Tissue Regeneration

Takao Fukuda,Terukazu Sanui

doi:10.4172/2168-9431.1000137

Abstract

Amelogenin, the major component of a commercial enamel matrix derivative (Straumann® Emdogain), is commonly employed in periodontology. It is mainly used in periodontal surgery to stimulate the regeneration of periodontal tissues, including the cementum, periodontal ligament, and alveolar bone. However, the precise molecular mechanisms underlying amelogenin-induced regeneration have not yet been elucidated. Thus, to gain further insight into how amelogenin induces periodontal tissue regeneration, we performed a protein interaction screen using recombinant full-length amelogenin (rM180) as bait. Coupling affinity chromatography with proteomic analysis identified glucose-regulated protein 78 (Grp78) as a new amelogenin-binding protein. We further demonstrated that the interaction between amelogenin and Grp78 not only contributes to cell proliferation in osteoblastic cells but also enhances cell migration in periodontal ligament stem/progenitor cells. Although the potentiation effects of Grp78 should be further examined in vivo, our findings indicate the significant therapeutic potential for amelogenin-induced periodontal tissue regeneration.

Highlights

Amelogenin, the major component of a commercial enamel matrix derivative (Straumann® Emdogain), is commonly employed in periodontology
After confirming the endocytosis of recombinant amelogenin as a precondition for physiological interaction, we found that glucose-regulated protein 78 (Grp78) was the only protein present in both the cytosolic and membrane fractions of the osteoblastic cell lysate
Recent studies have demonstrated that endoplasmic reticulum (ER) stress signaling mediates bone formation [15], and we found that the biological interaction between amelogenin and Grp78 contributed to osteoblastic cell proliferation

Summary

Introduction

Amelogenin, the major component of a commercial enamel matrix derivative (Straumann® Emdogain), is commonly employed in periodontology. The ECM is well known to serve as a biological scaffold for tissue regeneration by modulating cells through the transduction of a variety of signaling pathways [2]. Many in vitro studies have supported the notion that EMD contributes to osteoconductive activity [6] and enhances the multi-lineage differentiation of human PDL cells [7].

Results

Conclusion