Hydrogen sulfide promotes osteogenic differentiation of human periodontal ligament cells via p38-MAPK signaling pathway under proper tension stimulation

Abstract

ObjectiveHydrogen sulfide (H2S), one of endogenous gaseous signalling molecules, can be induced by mechanical force stimulation on human periodontal ligament cells (hPDLCs). Little is known about the mechanism of H2S on the osteogenic differentiation although previous studies have demonstrated that H2S stimulated or inhibited osteoclastic differentiation. The present study was to investigate whether H2S played a regulatory role in osteogenic differentiation of the periodontal tissue remodeling and the involvement of mitogen-activated protein kinase (MAPK) signaling in this process. DesignhPDLCs were applied with cycle tension force for 6h, 12h, 24h or 48h to select the optimal time for force application. Then the effects of H2S on hPDLCs osteogenic differentiation were investigated. Signal-regulated kinases p38-MAPK and ERK activities with H2S treatment were measured. Finally, specific MAPK inhibitors SB203580 and U0126 were employed to investigate the involvement of the two kinases in hPDLCs osteogenic differentiation with H2S pre-treatment. ResultsTension stimulation promoted mRNA and protein expression of ALP, OCN and Runx2 in hPDLCs. The expression of ALP, OCN and Runx2 increased in a concentration-dependent manner with H2S pre-treatment. Importantly, p38-MAPK and ERK were activated in different ways upon induction by H2S. Furthermore, expression of Runx2, ALP and OCN, the osteogenic regulators, was reversed by SB203580 and U0126. ConclusionsH2S could promote osteogenic differentiation of hPDLCs by activating p38-MAPK and ERK signaling pathways.