The effect of BMP9 on inflammation in the early stage of pulpitis

Bone morphogenetic protein 9 (BMP9) might be associated with inflammatory responses to different diseases, but its relationship with pulpitis is unknown. Objective: The purpose of this study was to explore the effects and mechanism of BMP9 in pulpitis. Methodology: A rat pulpitis model was established for detecting BMP9 expression, which was also examined in Porphyromonas gingivalis lipopolysaccharide (P.g. LPS)-stimulated human dental pulp cells (hDPCs). Then, the effects and mechanism of BMP9 on the regulation of inflammatory factors and matrix metalloproteinase 2 (MMP2) were detected using real-time quantitative PCR, western blotting, and immunocytofluorescence. In addition, the migration ability of THP-1 monocyte-macrophages, treated with inflammatory supernate inhibited by BMP9, was preliminarily tested by transwell assay. Finally, a direct pulp-capping model in rats was constructed to determine the influence of BMP9 overexpression on pulpitis in vivo. Results: BMP9 expression decreased at 24 h and increased at 3 and 7 d in rat pulpitis and inflammatory hDPCs. BMP9 overexpression inhibited the gene expression of inflammatory factors IL-6, IL-8, and CCL2 and the secretion of IL-6 and MMP2 proteins in P.g. LPS-stimulated hDPCs. Furthermore, phosphorylated Smad1/5 level was upregulated, and phosphorylated ERK and JNK levels were downregulated. The inflammatory supernate of hDPCs inhibited by BMP9 further reduced the migration of THP-1 cells. In rat pulp-capping models, overexpressed BMP9 could partially restrain the development of dental pulp inflammation. Conclusions: This study is the first to confirm that BMP9 is involved in the occurrence and development of pulpitis and can partially inhibit pulpitis severity in the early stage. These findings provided a theoretical reference for further studies on the mechanism of pulpitis and the application of bioactive molecules in vital pulp therapy.