Journal
FEBS OPEN BIO
Volume 6, Issue 12, Pages 1310-1319Publisher
WILEY
DOI: 10.1002/2211-5463.12151
Keywords
extracellular-regulated kinase; outer membrane vesicle; Porphyromonas gingivalis; runt-related transcription factor 2; vascular calcification
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Funding
- Science and Technology Project of Beijing [2014JY0330]
- Healthy Care Program of the People's Liberation Army [14BJZ10]
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The outer membrane vesicle (OMV) derived from Porphyromonas gingivalis plays an essential role in causing inflammation which, in turn, plays an important part in the pathogenesis of cardiovascular diseases such as atherosclerosis and thromboembolism. However, the contribution of oral bacteria to vascular calcification is yet to be determined. Here, we evaluated the effect of OMV on vascular smooth muscle cell (VSMC) calcification both in vitro and ex vivo. We established a reproducible P. gingivalis OMV-induced differentiation and calcification model of VSMCs in vitro. The results indicate that OMV promotes VSMC calcification in a concentration-dependent manner, modulating the expression of bone markers and SMC markers both on genes and proteins that are important for osteoblastic differentiation and mineralization of VSMCs. We also showed that the key osteogenic transcription factor, runt-related transcription factor 2 (Runx2), which is affected by upstream extracellular-regulated kinase (ERK) signaling, is a key regulator of OMV-induced VSMC differentiation and calcification. Taken together, our research demonstrates that Runx2 is a crucial component of OMV- induced calcification of VSMCs, and ERK signaling plays a vital role in mediating Runx2 up-regulation and VSMC calcification.
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