Reference - Detail
| RRC ID | 61912 |
|---|---|
| Author | Nakamura K, Shirai T, Morishita S, Uchida S, Saeki-Miura K, Makishima F. |
| Title | p38 mitogen-activated protein kinase functionally contributes to chondrogenesis induced by growth/differentiation factor-5 in ATDC5 cells. |
| Journal | Exp Cell Res |
| Abstract |
Recent studies of intracellular signal transduction mechanisms for the transforming growth factor-beta (TGF-beta) superfamily have focused on Smad proteins, but have paid little attention to mitogen-activated protein (MAP) kinase cascades. Here we demonstrate that growth/differentiation factor-5 (GDF-5), but neither bone morphogenetic protein-2 (BMP-2) nor TGF-beta1, fully promotes the early phase of the chondrogenic response by inducing cellular condensation followed by cartilage nodule formation in a mouse chondrogenic cell line, ATDC5. We investigated which, if any, of the three major types of MAP kinase plays a functional role in the promotion of chondrogenesis induced by GDF-5. GDF-5 induced phosphorylation of p38 MAP kinase and extracellular signal-regulated kinase (ERK) but not that of c-Jun N-terminal kinase (JNK). The phosphorylation of p38 MAP kinase was also induced by BMP-2 and TGF-beta1. An inhibitor of p38 and p38 beta MAP kinase, SB202190, showed complete inhibition of cartilage nodule formation but failed to affect alkaline phosphatase (ALP) activity induced by GDF-5. Expression of the type II collagen gene, a hallmark of chondrogenesis in vertebrates, was also induced by GDF-5 treatment and strongly suppressed by SB202190. On the other hand, although an inhibitor of MAP/ERK kinase, PD98059, inhibited the rapid phosphorylation of ERK by GDF-5, it inhibited neither ALP activity nor cartilage nodule formation induced by GDF-5. These results strongly suggest that the p38 MAP kinase cascade is involved in GDF-5 signaling pathways and that a role of the p38 MAP kinase pathway is necessary over a longer period to promote chondrogenesis in ATDC5 cells. |
| Volume | 250(2) |
| Pages | 351-63 |
| Published | 1999-8-1 |
| DOI | 10.1006/excr.1999.4535 |
| PII | S0014-4827(99)94535-4 |
| PMID | 10413589 |
| MeSH | Alkaline Phosphatase / metabolism Animals Bone Morphogenetic Protein 2 Bone Morphogenetic Proteins / pharmacology Calcium-Calmodulin-Dependent Protein Kinases / antagonists & inhibitors Calcium-Calmodulin-Dependent Protein Kinases / metabolism* Carcinoma, Embryonal Cartilage / drug effects Cartilage / metabolism Cell Differentiation / drug effects Cell Size / drug effects Chondrogenesis / drug effects* Collagen / genetics Dose-Response Relationship, Drug Enzyme Induction / drug effects Growth Differentiation Factor 5 Growth Substances / pharmacology* Humans JNK Mitogen-Activated Protein Kinases MAP Kinase Kinase 1 Mice Mitogen-Activated Protein Kinase Kinases* Mitogen-Activated Protein Kinases* Phosphorylation / drug effects Protein Serine-Threonine Kinases / antagonists & inhibitors Protein Serine-Threonine Kinases / metabolism Protein-Tyrosine Kinases / antagonists & inhibitors Protein-Tyrosine Kinases / metabolism RNA, Messenger / genetics RNA, Messenger / metabolism Signal Transduction / drug effects Transforming Growth Factor beta / pharmacology Tumor Cells, Cultured p38 Mitogen-Activated Protein Kinases |
| IF | 3.383 |
| Altmetric score |
オルトメトリクス指標項目
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| The most frequently cited source | Patent(IFI CLAIMS) |
| Total number of mentions | 20 |
| Altmetric score changes over past 6months | 0.0 |
| Resource | |
| Human and Animal Cells | ATDC5(RCB0565) |