title: Bone morphogenetic protein-2 counterregulates interleukin-18 mRNA and protein in MC3T3-E1 mouse osteoblastic cells.
abstract: Fibroblast growth factors-2 (FGF-2) and bone morphogenetic protein-2 (BMP-2) are two of the main factors that regulate differentiation of osteoblasts. Interleukin-18 (IL-18), originally cloned as an interferon gamma-inducing factor, has been reported to inhibit maturation of osteoclasts by upregulation of osteoprotegerin secreted from osteoblasts. Little is known about the functional relationship between IL-18 and the two growth factors in osteoblast differentiation. To better understand this relationship, we analyzed the effect of BMP-2 and FGF-2 on the mRNA expression levels of IL-18, as well as IL-1alpha and IL-6, in MC3T3-E1 mouse osteoblastic cells. Following this, the effects of BMP-2 on the expression of IL-18 protein and caspase-1 protein were analyzed by immunofluorescence staining. Real-time PCR and immunofluorescence staining analysis showed that FGF-2 had no effect on the expression of IL-18 mRNA and protein, but while BMP-2 reduced IL-18 mRNA levels, increased immunostaining of both IL-18 protein and caspase-1 protein was detected in BMP-2-treated MC3T3-E1 cells. Although the significance and mechanisms of this counterregulation of IL-18 mRNA and protein were not determined in this study, the increase of IL-18 protein suggested that BMP-2 may induce an active form of IL-18.
authors.affiliation: Department of Obstetrics and Gynecology, Hyogo College of Medicine, Hyogo, Japan.
authors.forename: Masateru
authors.initials: M
authors.lastname: Hori
authors.forename: Hideaki
authors.initials: H
authors.lastname: Sawai
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Tsuji
authors.forename: Haruki
authors.initials: H
authors.lastname: Okamura
authors.forename: Koji
authors.initials: K
authors.lastname: Koyama
mesh_terms: D000469:Alkaline Phosphatase / Q000378:metabolism; D000818:Animals; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins / Q000494:pharmacology*; D020170:Caspase 1 / Q000378:metabolism; D002460:Cell Line; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects*; D007375:Interleukin-1 / Q000235:genetics / Q000378:metabolism; D020382:Interleukin-18 / Q000235:genetics* / Q000378:metabolism; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism; D051379:Mice; D010006:Osteoblasts / Q000187:drug effects* / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism*; D011994:Recombinant Proteins / Q000494:pharmacology; D013997:Time Factors; D016212:Transforming Growth Factor beta / Q000494:pharmacology*
chemical_list: C525719:Bmp2 protein, mouse; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins; D007375:Interleukin-1; D020382:Interleukin-18; D015850:Interleukin-6; D012333:RNA, Messenger; D011994:Recombinant Proteins; D016212:Transforming Growth Factor beta; D016222:Fibroblast Growth Factor 2; D000469:Alkaline Phosphatase; D020170:Caspase 1