title: Interleukin 17 inhibits myogenic and promotes osteogenic differentiation of C2C12 myoblasts by activating ERK1,2.
abstract: The present study evaluated the role of interleukin (IL) 17 in multilineage commitment of C2C12 myoblastic cells and investigated associated signaling pathways. The results concerning the effects on cell function showed that IL-17 inhibits the migration of C2C12 cells, while not affecting their proliferation. The data regarding the influence on differentiation demonstrated that IL-17 inhibits myogenic differentiation of C2C12 cells by down-regulating the myogenin mRNA level, myosin heavy chain expression and myotube formation, but promotes their osteogenic differentiation by up-regulating the Runt-related transcription factor 2 mRNA level, cyclooxygenase-2 expression and alkaline phosphatase activity. IL-17 exerted these effects by activating ERK1,2 mitogen activated protein kinase signaling pathway, which in turn regulated the expression of relevant genes and proteins to inhibit myogenic differentiation and induce osteogenic differentiation. Additional analysis showed that the induction of osteogenic differentiation by IL-17 is independent of BMP signaling. The results obtained demonstrate the potential of IL-17 not only to inhibit the myogenic differentiation of C2C12 myoblasts but also to convert their differentiation pathway into that of osteoblast lineage providing new insight into the capacities of IL-17 to modulate the differentiation commitment.
authors.affiliation: Institute for Medical Research, University of Belgrade, Belgrade, Serbia. jelena.kocic@imi.bg.ac.rs
authors.forename: Jelena
authors.initials: J
authors.lastname: Kocić
authors.forename: Juan F
authors.initials: JF
authors.lastname: Santibañez
authors.forename: Aleksandra
authors.initials: A
authors.lastname: Krstić
authors.forename: Slavko
authors.initials: S
authors.lastname: Mojsilović
authors.forename: Ivana Okić
authors.initials: IO
authors.lastname: Dorđević
authors.forename: Drenka
authors.initials: D
authors.lastname: Trivanović
authors.forename: Vesna
authors.initials: V
authors.lastname: Ilić
authors.forename: Diana
authors.initials: D
authors.lastname: Bugarski
mesh_terms: D000818:Animals; D019485:Bone Morphogenetic Proteins / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects*; D002460:Cell Line; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D004789:Enzyme Activation / Q000187:drug effects; D020381:Interleukin-17 / Q000494:pharmacology*; D020935:MAP Kinase Signaling System / Q000187:drug effects; D051379:Mice; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism*; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism*; D008954:Models, Biological; D024510:Muscle Development / Q000187:drug effects*; D032446:Myoblasts / Q000166:cytology* / Q000187:drug effects / Q000201:enzymology; D010012:Osteogenesis / Q000187:drug effects*; D053722:Receptors, Interleukin-17 / Q000378:metabolism
chemical_list: D019485:Bone Morphogenetic Proteins; D020381:Interleukin-17; D053722:Receptors, Interleukin-17; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3