Protein expression and inflammatory response after delivery of mRNA encoding platelet-derived growth factor-BB in sucrose citrate buffer into rat gingiva

Abstract

Messenger RNA (mRNA) has emerged as a novel therapeutic modality in medical fields, including regenerative medicine. The concept of mRNA-based therapy is to use synthesized mRNA encoding therapeutic protein delivered to target tissue. Thus, mRNA encoding growth factor could be a promising alternative to recombinant protein. Platelet-derived growth factor (PDGF) is one of most extensively studied growth factors for periodontal regeneration. To date, mRNA therapy has never been explored in the field of periodontal regeneration. The aim of the study is to examine the effect of nucleoside-modified mRNA encoding PDGF-BB on the level of PDGF-BB protein and inflammatory response at local tissue upon intragingival injection. Sprague-Dawley rats were injected with pseudouridine-modified mRNA encoding PDGF-BB in sucrose citrate buffer at palatal gingiva. Gingiva was collected at day 1, 2, 3, 5 and 7 for analysis of PDGF-BB, VEGF-A protein and pro-inflammatory cytokines IL-6 and TNF-a, using ELISA. The results showed that intragingival injection of pseudouridine-modified mRNA encoding PDGF-BB significantly promoted transient PDGF-BB protein expression up to 40 to 100-fold as compared to control. PDGF-BB level peaked at 24-hour post-injection and declined to baseline within 3 days. Neither IL-6 nor TNF-a in gingiva were affected. The findings from this study demonstrated the potential of mRNA for periodontal regeneration.