title: Staurosporine induces chondrogenesis of chick embryo wing bud mesenchyme in monolayer cultures through canonical and non-canonical TGF-β pathways.
abstract: Staurosporine has been known to induce chondrogenesis in monolayer cultures of mesenchymal cells by dissolving actin stress fibers. The aim of this study was to further elucidate how the alteration of actin filaments by staurosporine induces chondrogenesis. Specifically, we examined whether the transforming growth factor (TGF)-β pathway is implicated. SB505124 strongly suppressed staurosporine-induced chondrogenesis without affecting the drug's action on the actin cytoskeleton. Staurosporine increased the phosphorylation of TGF-β receptor I (TβRI) but had no significant effect on the expression levels of TGF-β1, TGF-β2, TGF-β3, TβRI, TβRII, and TβRIII. Phosphorylation of Smad2 and Smad3 was not increased by staurosporine. However, SB505124 almost completely suppressed the phosphorylation of Smad2 and Smad3. In addition, inhibition of Smad3 blocked staurosporine-induced chondrogenesis. Inhibition of Akt, p38 mitogen-activated protein kinase (MAPK), and c-jun N-terminal kinase (JNK) suppressed chondrogenesis induced by staurosporine. Phosphorylation of Akt, p38 MAPK, and JNK was increased by staurosporine. SB505124 reduced the phosphorylation of Akt and p38 MAPK, while it had no effect on the phosphorylation of JNK. The phosphorylation level of extracellular signal-regulated kinase (ERK) was not significantly affected by staurosporine. In addition, inhibition of ERK with PD98059 alone did not induce chondrogenesis. Taken together, these results suggest that staurosporine induces chondrogenesis through TGF-β pathways including canonical Smads and non-canonical Akt and p38 MAPK signaling.
authors.affiliation: Department of Biology, College of Natural Sciences, Kyungpook National University, 80 Daehakoro, Daegu, 41566, Korea.
authors.forename: Hyoin
authors.initials: H
authors.lastname: Kim
authors.affiliation: Department of Biology, College of Natural Sciences, Kyungpook National University, 80 Daehakoro, Daegu, 41566, Korea.
authors.forename: Kyungmin
authors.initials: K
authors.lastname: Kei
authors.affiliation: Department of Biology, College of Natural Sciences, Kyungpook National University, 80 Daehakoro, Daegu, 41566, Korea. sonnjk@knu.ac.kr.
authors.forename: Jong Kyung
authors.initials: JK
authors.lastname: Sonn
mesh_terms: D008841:Actin Cytoskeleton / Q000187:drug effects; D000818:Animals; D052117:Benzodioxoles / Q000494:pharmacology; D002642:Chick Embryo; D020219:Chondrogenesis / Q000187:drug effects*; D007093:Imidazoles / Q000494:pharmacology; D008648:Mesoderm / Q000187:drug effects / Q000254:growth & development; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics; D011725:Pyridines / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects; D051785:Smad Proteins / Q000235:genetics; D019311:Staurosporine / Q000494:pharmacology*; D016212:Transforming Growth Factor beta / Q000235:genetics* / Q000378:metabolism; D014921:Wings, Animal / Q000187:drug effects* / Q000254:growth & development; D048051:p38 Mitogen-Activated Protein Kinases / Q000235:genetics
chemical_list: C519132:2-(5-benzo(1,3)dioxol-5-yl-2-tert-butyl-3H-imidazol-4-yl)-6-methylpyridine hydrochloride; D052117:Benzodioxoles; D007093:Imidazoles; D011725:Pyridines; D051785:Smad Proteins; D016212:Transforming Growth Factor beta; D051057:Proto-Oncogene Proteins c-akt; D048051:p38 Mitogen-Activated Protein Kinases; D019311:Staurosporine
keywords: Chondrogenesis; Cytoskeleton; Staurosporine; TGF-β