RRC ID 54919
著者 Kusuyama J, Amir MS, Albertson BG, Bandow K, Ohnishi T, Nakamura T, Noguchi K, Shima K, Semba I, Matsuguchi T.
タイトル JNK inactivation suppresses osteogenic differentiation, but robustly induces osteopontin expression in osteoblasts through the induction of inhibitor of DNA binding 4 (Id4).
ジャーナル FASEB J
Abstract Osteoblasts are versatile cells involved in multiple whole-body processes, including bone formation and immune response. Secretory amounts and patterns of osteoblast-derived proteins such as osteopontin (OPN) and osteocalcin (OCN) modulate osteoblast function. However, the regulatory mechanism of OPN and OCN expression remains unknown. Here, we demonstrate that p54/p46 c-jun N-terminal kinase (JNK) inhibition suppresses matrix mineralization and OCN expression but increases OPN expression in MC3T3-E1 cells and primary osteoblasts treated with differentiation inducers, including ascorbic acid, bone morphogenic protein-2, or fibroblast growth factor 2. Preinhibition of JNK before the onset of differentiation increased the number of osteoblasts that highly express OPN but not OCN (OPN-OBs), indicating that JNK affects OPN secretory phenotype at the early stage of osteogenic differentiation. Additionally, we identified JNK2 isoform as being critically involved in OPN-OB differentiation. Microarray analysis revealed that OPN-OBs express characteristic transcription factors, cell surface markers, and cytokines, including glycoprotein hormone α2 and endothelial cell-specific molecule 1. Moreover, we found that inhibitor of DNA binding 4 is an important regulator of OPN-OB differentiation and that dual-specificity phosphatase 16, a JNK-specific phosphatase, functions as an endogenous regulator of OPN-OB induction. OPN-OB phenotype was also observed following LPS from Porphyromonas gingivalis stimulation during osteogenic differentiation. Collectively, these results suggest that the JNK-Id4 signaling axis is crucial in the control of OPN and OCN expression during osteoblastic differentiation.-Kusuyama, J., Amir, M. S., Albertson, B. G., Bandow, K., Ohnishi, T., Nakamura, T., Noguchi, K., Shima, K., Semba, I., Matsuguchi, T. JNK inactivation suppresses osteogenic differentiation, but robustly induces osteopontin expression in osteoblasts through the induction of inhibitor of DNA binding 4 (Id4).
巻・号 33(6)
ページ 7331-7347
公開日 2019-6-1
DOI 10.1096/fj.201802465R
PMID 30884976
MeSH Animals Cells, Cultured Dual-Specificity Phosphatases / deficiency Dual-Specificity Phosphatases / physiology Gene Expression Regulation, Developmental / drug effects Inhibitor of Differentiation Proteins / physiology* JNK Mitogen-Activated Protein Kinases / antagonists & inhibitors JNK Mitogen-Activated Protein Kinases / physiology* MAP Kinase Signaling System / drug effects MAP Kinase Signaling System / physiology* Mice Mice, Inbred C57BL Mice, Knockout Mitogen-Activated Protein Kinase 9 / antagonists & inhibitors Mitogen-Activated Protein Kinase 9 / physiology Mitogen-Activated Protein Kinase Phosphatases / deficiency Mitogen-Activated Protein Kinase Phosphatases / physiology Osteoblasts / metabolism* Osteocalcin / biosynthesis Osteocalcin / genetics Osteogenesis / drug effects Osteogenesis / physiology* Osteopontin / biosynthesis* Osteopontin / genetics Protein Isoforms / physiology RNA Interference RNA, Small Interfering / genetics RNA, Small Interfering / pharmacology
IF 5.391
引用数 3
リソース情報
ヒト・動物細胞 MC3T3-E1(RCB1126)