IL-6 induces osteoblastic differentiation of periodontal ligament cells.
Interleukin (IL)-6 has been considered as an osteolytic factor involved in periodontal disease. However, the function of IL-6 in osteoblastic differentiation of periodontal ligament cells is not clear. We examined the effects of IL-6 and its soluble receptor (sIL-6R) on osteoblastic differentiation of periodontal ligament cells. Osteoblastic differentiation was induced by ascorbic acid. Osteoblast markers, including alkaline phosphatase activity and Runx2 gene expression, were examined. The mechanism of action of IL-6 on osteoblastic differentiation was evaluated by insulin-like growth factor (IGF)-I production and specific inhibitors for the IL-6-signaling molecule. IL-6/sIL-6R enhanced alkaline phosphatase activity and Runx2. Alkaline phosphatase activity was reduced by anti-IGF-I antibody. Mitogen-activated protein kinase and Janus protein tyrosine kinase inhibitors diminished alkaline phosphatase induced by IL-6/sIL-6R. We conclude that IL-6/sIL-6R increases ascorbic-acid-induced alkaline phosphatase activity through IGF-I production, implying that IL-6 acts not only as an osteolytic factor, but also as a mediator of osteoblastic differentiation in periodontal ligament cells.
Iwasaki
K
K
Department of Hard Tissue Engineering-Periodontology, Tokyo Medical and Dental University Graduate School, 1-5-45 Yushima, Bunkyoku, Tokyo 113-8549, Japan.
Komaki
M
M
Mimori
K
K
Leon
E
E
Izumi
Y
Y
Ishikawa
I
I
D000293:Adolescent; D000328:Adult; D000469:Alkaline Phosphatase / Q000096:biosynthesis; D001205:Ascorbic Acid / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology; D050659:Core Binding Factor Alpha 1 Subunit / Q000096:biosynthesis; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000096:biosynthesis; D015850:Interleukin-6 / Q000494:pharmacology / Q000502:physiology*; D020935:MAP Kinase Signaling System; D010006:Osteoblasts / Q000166:cytology* / Q000378:metabolism; D010513:Periodontal Ligament / Q000166:cytology* / Q000187:drug effects; D019947:Receptors, Interleukin-6 / Q000502:physiology; D055815:Young Adult
D050659:Core Binding Factor Alpha 1 Subunit; D015850:Interleukin-6; C493709:RUNX2 protein, human; D019947:Receptors, Interleukin-6; D007334:Insulin-Like Growth Factor I; D000469:Alkaline Phosphatase; D001205:Ascorbic Acid