Combined application of geranylgeranylacetone and amelogenin promotes angiogenesis and wound healing in human periodontal ligament cells

Amelogenin directly binds to glucose-regulated protein 78 (Grp78). Cell migration activity is expected increase when human periodontal ligament cells (hPDLCs) overexpressing Grp78 are treated with amelogenin. Geranylgeranylacetone (GGA) a drug that induces the expression of heat shock and routinely used treat gastric ulcers. Here, we investigated changes in properties behavior hPDLCs response treatment GGA synergistic effects amelogenin stimulation pretreated for establishment novel tissue regenerative therapy. We observed increased enhanced cell migration. Microarray analysis demonstrated triggered production angiopoietin-like 4 amphiregulin, which involved enhancement angiogenesis subsequent wound healing via activation hypoxia-inducible factor 1α peroxisome proliferator-activated receptors as well phosphorylation cAMP element-binding kinase A. Moreover, addition recombinant murine (rM180) further accelerated hPDLC tube formation umbilical vein endothelial due upregulation interleukin-8 (IL-8), monocyte chemotactic 1, IL-6, also known angiogenesis-inducing factors. These findings suggest application gingival alveolar bone damaged by disease would facilitate process inducing migrate root surface release cytokines repair. Additionally, supplementation synergistically migratory capacity these while actively promoting angiogenesis. Therefore, combined may establish suitable environment drive development therapeutics regeneration.