Oral Malodorous Compound Inhibits Osteoblast Proliferation

Background: Oral malodorous compounds including hydrogen sulfide (H2S) are causative agents of periodontitis because the toxicities are similar to that of cyanate. Previous studies demonstrated that volatile sulfur compounds (VSCs) were highly toxic to periodontal tissues, causing a large reduction in the amount of collagen in human gingival fibroblasts and extracellular matrix as well as, for example, apoptosis, immunologic responses, and matrix metalloproteinase production. The objective of this study was to determine the effect of H2S on the proliferation of osteoblasts and a signaling transduction pathway through the mitogen-activated protein kinase (MAPK). Methods: Normal human osteoblasts (NHOst) and murine osteoblasts (cell line MC3T3-E1) were incubated with H2S Cell proliferation was assessed by measuring [H-3]thymidine incorporation. The effects of H2S on the signal transduction pathways, the MAPK cascade, that control cell proliferation were evaluated in NHOst by determining extracellular signal-regulated kinase (ERK)1/2 and p38 phosphorylation with a Western blot analysis. Results: After incubating NHOst with H2S for 24 hours, [H-3]thymidine incorporation into the DNA significantly decreased dose - dependently with H2S. At a concentration of 100 ng/ml H2S, [H-3]thymidine incorporation decreased 79% compared to the control. Similar results were obtained from MC3T3-E1. The phosphorylation of ERK1/2 and p38 was increased by H2S at 10 minutes after starting the treatment and then decreased time dependently. The activation of ERK1/2 and p38 induced by H2S was inhibited by the specific inhibitor of MAPK/ERK kinase ([MEK]; U0126) or p38 (SB203580). Conclusion: H2S inhibited the proliferation of human osteoblastic cells through the MAPK pathway. J Periodontol 2009; 80:2028-2034.