Reference - Detail
| RRC ID | 54919 |
|---|---|
| Author | Kusuyama J, Amir MS, Albertson BG, Bandow K, Ohnishi T, Nakamura T, Noguchi K, Shima K, Semba I, Matsuguchi T. |
| Title | JNK inactivation suppresses osteogenic differentiation, but robustly induces osteopontin expression in osteoblasts through the induction of inhibitor of DNA binding 4 (Id4). |
| Journal | 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). |
| Volume | 33(6) |
| Pages | 7331-7347 |
| Published | 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 |
| Times Cited | 3 |
| Altmetric score |
オルトメトリクス指標項目
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| The most frequently cited source | X(Twitter) |
| Total number of mentions | 4 |
| Altmetric score changes over past 6months | 0.0 |
| Resource | |
| Human and Animal Cells | MC3T3-E1(RCB1126) |