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JNK inactivation suppresses osteogenic differentiation, but robustly induces osteopontin expression in osteoblasts through the induction of inhibitor of DNA binding 4 (Id4)
- Source :
- The FASEB Journal. 33:7331-7347
- Publication Year :
- 2019
- Publisher :
- Wiley, 2019.
-
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
- Subjects :
- musculoskeletal diseases
0301 basic medicine
MAP Kinase Signaling System
Osteocalcin
Biochemistry
Mice
03 medical and health sciences
chemistry.chemical_compound
0302 clinical medicine
Immune system
Osteogenesis
Genetics
Animals
Mitogen-Activated Protein Kinase 9
Protein Isoforms
Bone formation
Osteopontin
RNA, Small Interfering
Molecular Biology
Cells, Cultured
Mice, Knockout
Osteoblasts
biology
Chemistry
JNK Mitogen-Activated Protein Kinases
Gene Expression Regulation, Developmental
Cell biology
Mice, Inbred C57BL
030104 developmental biology
biology.protein
Dual-Specificity Phosphatases
Mitogen-Activated Protein Kinase Phosphatases
Inhibitor of Differentiation Proteins
RNA Interference
030217 neurology & neurosurgery
DNA
Biotechnology
Subjects
Details
- ISSN :
- 15306860 and 08926638
- Volume :
- 33
- Database :
- OpenAIRE
- Journal :
- The FASEB Journal
- Accession number :
- edsair.doi.dedup.....edf6bcb23c613ec88a7d6e9e6fe80544