title: Porphyromonas gingivalis-derived outer membrane vesicles promote calcification of vascular smooth muscle cells through ERK1/2-RUNX2.
abstract: The outer membrane vesicle (OMV) derived fromPorphyromonas gingivalisplays 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 bothin vitroandex vivo. We established a reproducibleP. gingivalisOMV-induced differentiation and calcification model of VSMCsin 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.
authors.affiliation: Department of Stomatology Aviation General Hospital of China Medical University Beijing China.
authors.forename: Wen Wei
authors.initials: WW
authors.lastname: Yang
authors.affiliation: Department of Stomatology Aviation General Hospital of China Medical University Beijing China; Department of Stomatology The General Hospital of Chinese People's Liberation Beijing China.
authors.forename: Bin
authors.initials: B
authors.lastname: Guo
authors.affiliation: Department of Periodontics West China College of Stomatology Sichuan University Chengdu China.
authors.forename: Wen Yuan
authors.initials: WY
authors.lastname: Jia
authors.affiliation: Department of Stomatology Aviation General Hospital of China Medical University Beijing China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Jia
keywords: Porphyromonas gingivalis; extracellular‐regulated kinase; outer membrane vesicle; runt‐related transcription factor 2; vascular calcification