Histatin‐1 is a novel osteogenic factor that promotes bone cell adhesion, migration, and differentiation

Abstract

Histatin-1 is a salivary antimicrobial peptide involved in the maintenance of enamel and oral mucosal homeostasis. Moreover, Histatin-1 has been shown to promote re-epithelialization in soft tissues, by stimulating cell adhesion and migration in oral and dermal keratinocytes, gingival and skin fibroblasts, endothelial cells and corneal epithelial cells. The broad-spectrum activity of Histatin-1 suggests that it behaves as a universal wound healing promoter, although this is far from being clear yet. Here, we report that Histatin-1 is a novel osteogenic factor that promotes bone cell adhesion, migration and differentiation. Specifically, Histatin-1 promoted cell adhesion, spreading and migration of SAOS-2 cells and MC3T3-E1 pre-osteoblasts in vitro, when placed on a fibronectin matrix. Besides, Histatin-1 induced the expression of osteogenic genes, including osteocalcin, osteopontin and Runx2, and increased both activity and protein levels of alkaline phosphatase. Furthermore, Histatin-1 promoted mineralization in vitro, as it augmented the formation of calcium deposits in both SAOS-2 and MC3T3-E1 cells. Mechanistically, although Histatin-1 failed to activate ERK1/2, FAK and Akt, which are signaling proteins associated with osteogenic differentiation or cell migration, it triggered nuclear re-localization of β-catenin. Strikingly, the effects of Histatin-1 were recapitulated in cells that are non-osteogenically committed, since it promoted surface adhesion, migration and the acquisition of osteogenic markers in primary mesenchymal cells derived from the apical papilla and dental pulp. Collectively, these observations indicate that Histatin-1 is a novel osteogenic factor that promotes bone cell differentiation, surface adhesion and migration, as crucial events required for bone tissue regeneration. This article is protected by copyright. All rights reserved.