title: JNK signaling plays an important role in the effects of TNF-α and IL-1β on in vitro osteoblastic differentiation of cultured human periosteal-derived cells.
abstract: The purpose of this study was to examine the effects of TNF-α and IL-1β on in vitro osteoblastic differentiation of cultured human periosteal-derived cells. To examine the effects of TNF-α and IL-1β on in vitro osteoblastic differentiation of cultured human periosteal-derived cells, the cells cultured in the osteogenic induction medium were treated with 0.1-10 ng/ml TNF-α and 0.01-1 ng/ml IL-1β. TNF-α and IL-1β enhanced the alkaline phosphatase (ALP) activity and alizarin red S staining in cultured human periosteal-derived cells. However, these cytokines did not stimulate the Runt-related transcription factor (Runx) 2 activity and osteocalcin secretion. The ALP activity was decreased in the periosteal-derived cells pretreated with mitogen activated protein kinase (MAPK) inhibitors and then treated with TNF-α or IL-1β. Among the periosteal-derived cells pretreated with MAPK inhibitors, the ALP activity was markedly decreased in the cells pretreated with SP 600125, the specific inhibitor of C-Jun N-terminal kinase (JNK). The periosteal-derived cells treated with TNF-α and IL-1β showed an increase in extracellular signal-regulated kinase (ERK) and JNK phosphorylation. Among the ERK and JNK phosphorylation, JNK phosphorylation was strongly observed in the cells. These results suggest that TNF-α and IL-1β increased the in vitro osteoblastic differentiation of cultured human periosteal-derived cells by enhancing the ALP activity and mineralization process, but not by Runx2 activation. The functional role of TNF-α and IL-1β in increasing the ALP activity and mineralization of periosteal-derived cells primarily depends on the JNK signaling among the MAPK pathways.
authors: Clinical Research Institute, Gyeongsang National University Hospital, Jinju, Republic of Korea.
authors: Young-Sool
authors: YS
authors: Hah
authors: Hea-Gea
authors: HG
authors: Kang
authors: Hee-Young
authors: HY
authors: Cho
authors: Sang-Hoon
authors: SH
authors: Shin
authors: Uk-Kyu
authors: UK
authors: Kim
authors: Bong-Wook
authors: BW
authors: Park
authors: Sang-il
authors: SI
authors: Lee
authors: Gyu-Jin
authors: GJ
authors: Rho
authors: Jong-Ryoul
authors: JR
authors: Kim
authors: June-Ho
authors: JH
authors: Byun
mesh_terms: D000469:Alkaline Phosphatase / Q000378:metabolism; D000704:Analysis of Variance; D000873:Anthracenes; D000880:Anthraquinones; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology*; D002478:Cells, Cultured; D050659:Core Binding Factor Alpha 1 Subunit / Q000378:metabolism; D017931:DNA Primers / Q000235:genetics; D006651:Histocytochemistry; D006801:Humans; D053583:Interleukin-1beta / Q000008:administration & dosage / Q000494:pharmacology*; D008156:Luciferases; D020935:MAP Kinase Signaling System / Q000502:physiology*; D010006:Osteoblasts / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D015675:Osteocalcin / Q000378:metabolism; D010521:Periosteum / Q000166:cytology / Q000502:physiology*; D010766:Phosphorylation / Q000187:drug effects; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014409:Tumor Necrosis Factor-alpha / Q000008:administration & dosage / Q000494:pharmacology*
chemical_list: D000873:Anthracenes; D000880:Anthraquinones; D050659:Core Binding Factor Alpha 1 Subunit; D017931:DNA Primers; D053583:Interleukin-1beta; C493709:RUNX2 protein, human; D014409:Tumor Necrosis Factor-alpha; D015675:Osteocalcin; C432165:pyrazolanthrone; C004468:Alizarin Red S; D008156:Luciferases; D000469:Alkaline Phosphatase
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