Antiosteoporosis effects of a marine antimicrobial peptide pardaxin via regulation of the osteogenesis pathway.

Antimicrobial peptides (AMPs) are known to play an important role in natural immunity. Moreover, the diverse biological activities of AMPs showed great potency in treating many diseases. Thus, in this study, we used an AMP, that is, pardaxin, from a marine fish (Pardachirus marmoratus), which has been reported to possess antibacterial and antitumor activities. We first investigated the mechanisms of pardaxin in promoting osteogenic differentiation in vitro and in vivo. As per our data, it was determined that pardaxin could stimulate bone morphogenetic protein-2 (BMP-2) and downstream cascade. The activation of BMP-2 could further induce the phosphorylation of Akt and extracellular signal-regulated kinase (ERK). Additionally, the activation of p-Akt and p-ERK could prompt the elevation and translocation of runt-related transcription factor 2 (runx-2), which is associated with osteoblast differentiation. The translocation of runx-2 initiated transcription and translation of osteogenesis-related markers, including alkaline phosphatase (ALP), osterix, and osteocalcin. Pardaxin significantly facilitated preosteoblast cells in mineralization and reversed dexamethasone- (DM-) induced zebrafish bone formation deficiency by activating the osteogenesis pathway. Therefore, we suggest that pardaxin could be a possible candidate for osteoporosis treatment and a promising therapeutic agent.