| 2885 Osteoprotegerin promotes survival and migration of human microvascular endothelial cells | ||
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M. KOBAYASHI-SAKAMOTO1, E. ISOGAI1, and K. HIROSE2, 1Health Sciences University of Hokkaido, Ishikari-Tobetsu, Japan, 2Ohu University, Koriyama, Japan Objective: Osteoprotegerin (OPG) is a key regulator of osteoclastogenesis. We recently reported that endothelial cells produce high levels of OPG in response to Porphyromonas gingivalis. We also indicated that OPG treatment protects human microvascular endothelial cells (HMVECs) from detachment and apoptotic cell death induced by gingipain-active bacterial cell extracts. These results suggest that osteoprotegerin acts as a survival factor for endothelial cells during periodontitis. However, the role of OPG in the endothelium remains unknown. In this study, we investigated the effects of OPG on HMVECs. Methods: HMVECs were incubated with or without OPG (1 μg/ml final concentration) under a serum-free condition for 4 days. Cell survival was assessed by a tetrazolium (WST-8) reduction assay. Cell migration was assessed by a wound-healing assay. The expression of integrin on the cell surface was determined using the integrin-mediated cell adhesion kit, which consists of plates coated with an anti-αvβ3 antibody. Results: Within 4 days of serum deprivation, 36.7% of OPG-treated HMVECs were viable, whereas only 20.0% of OPG-untreated HMVECs were viable (P < 0.05). Wound-healing assay revealed that within 22 h, the OPG-treated HMVECs migrated to fill approximately three-quarters of the wounded area when compared with the OPG-untreated cells that showed very little migration. Furthermore, the OPG treatment for 24 h under serum deprivation condition resulted in a significant increase in the surface expression of αvβ3 integrin on the HMVECs (P < 0.05). Conclusions: OPG protects HMVECs against serum-deprivation-induced cell death. Furthermore, OPG treatment of HMVECs promotes cell migration, and up-regulates αvβ3 expression. The αvβ3 mediates the endothelial cell survival pathway. Therefore, our results also suggest that OPG may regulate the endothelial cell survival by affecting the expression of αvβ3. This study was supported by a Grant-in-Aid for Scientific Research from MEXT, Japan (No.18592064). | ||
| Seq #294 - Immunology and Microbiology 10:45 AM-12:00 PM, Saturday, March 24, 2007 Ernest N. Morial Convention Center Exhibit Hall I2-J | ||
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