| Autor: |
Kusuyama J; Department of Oral Biochemistry, Field of Developmental Medicine, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan.; Department of Medicine, Section on Integrative Physiology and Metabolism, Joslin Diabetes Center, Harvard Medical School, Boston, Massachusetts, USA., Amir MS; Department of Oral Biochemistry, Field of Developmental Medicine, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan.; Department of Oral and Maxillofacial Surgery, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan.; Department of Oral and Maxillofacial Surgery, Faculty of Dentistry, Airlangga University, Surabaya, Indonesia., Albertson BG; Department of Medicine, Section on Integrative Physiology and Metabolism, Joslin Diabetes Center, Harvard Medical School, Boston, Massachusetts, USA., Bandow K; Department of Oral Biology and Tissue Engineering, Meikai University School of Dentistry, Saitama, Japan; and., Ohnishi T; Department of Oral Biochemistry, Field of Developmental Medicine, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan., Nakamura T; Department of Periodontology, Field of Oral and Maxillofacial Rehabilitation, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan., Noguchi K; Department of Periodontology, Field of Oral and Maxillofacial Rehabilitation, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan., Shima K; Department of Oral Pathology, Field of Oncology, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan., Semba I; Department of Oral Pathology, Field of Oncology, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan., Matsuguchi T; Department of Oral Biochemistry, Field of Developmental Medicine, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan. |
| Abstrakt: |
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). |
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