NF-kappaB-dependent induction of osteoprotegerin by Porphyromonas gingivalis in endothelial cells.
Porphyromonas gingivalis is a major etiological pathogen of adult periodontitis characterized by alveolar bone resorption. Vascular endothelial cells supply many inflammatory cytokines into periodontal tissue. However, whether the cells contribute to bone metabolism in periodontitis remains unknown. In this study, we investigated the effect of P. gingivalis on osteoprotegerin (OPG) and receptor activator of NF-kappaB ligand (RANKL) production, both of which are key regulators of bone metabolism, in human microvascular endothelial cells (HMVECs). We showed that P. gingivalis upregulated expression of OPG but not RANKL mRNA in HMVEC. P. gingivalis induced NF-kappaB activation, and the induction of OPG in HMVEC by the pathogen was blocked by the inhibitors of NF-kappaB. In addition, incubation of OPG with P. gingivalis supernatant resulted in loss of the protein. These results indicate that P. gingivalis-stimulated HMVEC secrete OPG via a NF-kappaB-dependent pathway, while the OPG is partly degraded by the bacteria. Thus, microvascular endothelial cells can act as a source of OPG and thereby may play an important role in regulating bone metabolism in periodontitis.
Kobayashi-Sakamoto
Michiyo
M
Department of Preventive Dentistry, Health Sciences University of Hokkaido, Ishikari-Tobetsu, 1757, Hokkaido 061-0293, Japan. mkoba@hoku-iryo-u.ac.jp
Hirose
Kimiharu
K
Isogai
Emiko
E
Chiba
Itsuo
I
D000975:Antioxidants / Q000494:pharmacology; D002352:Carrier Proteins / Q000378:metabolism; D003553:Cystine / Q000031:analogs & derivatives* / Q000494:pharmacology; D042783:Endothelial Cells / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000166:cytology; D010861:Fimbriae, Bacterial / Q000378:metabolism; D006023:Glycoproteins / Q000096:biosynthesis* / Q000378:metabolism; D006801:Humans; D008070:Lipopolysaccharides / Q000494:pharmacology; D008562:Membrane Glycoproteins / Q000378:metabolism; D008833:Microcirculation; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism*; D053244:Osteoprotegerin; D016966:Porphyromonas gingivalis / Q000166:cytology / Q000502:physiology*; D011759:Pyrrolidines / Q000494:pharmacology; D053245:RANK Ligand; D012333:RNA, Messenger / Q000096:biosynthesis; D053246:Receptor Activator of Nuclear Factor-kappa B; D018160:Receptors, Cytoplasmic and Nuclear / Q000096:biosynthesis* / Q000378:metabolism; D018124:Receptors, Tumor Necrosis Factor; D015842:Serine Proteinase Inhibitors / Q000494:pharmacology; D013859:Thiocarbamates / Q000494:pharmacology; D013997:Time Factors; D014107:Tosyllysine Chloromethyl Ketone / Q000494:pharmacology
D000975:Antioxidants; D002352:Carrier Proteins; D006023:Glycoproteins; D008070:Lipopolysaccharides; D008562:Membrane Glycoproteins; D016328:NF-kappa B; D053244:Osteoprotegerin; D011759:Pyrrolidines; D053245:RANK Ligand; D012333:RNA, Messenger; D053246:Receptor Activator of Nuclear Factor-kappa B; D018160:Receptors, Cytoplasmic and Nuclear; D018124:Receptors, Tumor Necrosis Factor; D015842:Serine Proteinase Inhibitors; C505686:TNFRSF11A protein, human; C506030:TNFRSF11B protein, human; C505688:TNFSF11 protein, human; D013859:Thiocarbamates; D014107:Tosyllysine Chloromethyl Ketone; C020972:pyrrolidine dithiocarbamic acid; D003553:Cystine; C030905:N-monoacetylcystine