Reference - Detail
| RRC ID | 18139 |
|---|---|
| Author | Chen L, Qanie D, Jafari A, Taipaleenmaki H, Jensen CH, Säämänen AM, Sanz ML, Laborda J, Abdallah BM, Kassem M. |
| Title | Delta-like 1/fetal antigen-1 (Dlk1/FA1) is a novel regulator of chondrogenic cell differentiation via inhibition of the Akt kinase-dependent pathway. |
| Journal | J Biol Chem |
| Abstract |
Delta-like 1 (Dlk1, also known as fetal antigen-1, FA1) is a member of Notch/Delta family that inhibits adipocyte and osteoblast differentiation; however, its role in chondrogenesis is still not clear. Thus, we overexpressed Dlk1/FA1 in mouse embryonic ATDC5 cells and tested its effects on chondrogenic differentiation. Dlk1/FA1 inhibited insulin-induced chondrogenic differentiation as evidenced by reduction of cartilage nodule formation and gene expression of aggrecan, collagen Type II and X. Similar effects were obtained either by using Dlk1/FA1-conditioned medium or by addition of a purified, secreted, form of Dlk1 (FA1) directly to the induction medium. The inhibitory effects of Dlk1/FA1 were dose-dependent and occurred irrespective of the chondrogenic differentiation stage: proliferation, differentiation, maturation, or hypertrophic conversion. Overexpression or addition of the Dlk1/FA1 protein to the medium strongly inhibited the activation of Akt, but not the ERK1/2, or p38 MAPK pathways, and the inhibition of Akt by Dlk1/FA1 was mediated through PI3K activation. Interestingly, inhibition of fibronectin expression by siRNA rescued the Dlk1/FA1-mediated inhibition of Akt, suggesting interaction of Dlk1/FA1 and fibronectin in chondrogenic cells. Our results identify Dlk1/FA1 as a novel regulator of chondrogenesis and suggest Dlk1/FA1 acts as an inhibitor of the PI3K/Akt pathways that leads to its inhibitory effects on chondrogenesis. |
| Volume | 286(37) |
| Pages | 32140-9 |
| Published | 2011-9-16 |
| DOI | 10.1074/jbc.M111.230110 |
| PII | S0021-9258(20)50924-1 |
| PMID | 21724852 |
| PMC | PMC3173234 |
| MeSH | Aggrecans / biosynthesis Aggrecans / genetics Animals Calcium-Binding Proteins Cell Differentiation / physiology* Cell Line Cell Proliferation Chondrogenesis / physiology* Collagen Type II / biosynthesis Collagen Type II / genetics Collagen Type X / biosynthesis Collagen Type X / genetics Embryonic Stem Cells / cytology Embryonic Stem Cells / metabolism* Enzyme Activation Fibronectins / biosynthesis Fibronectins / genetics Intercellular Signaling Peptides and Proteins / genetics Intercellular Signaling Peptides and Proteins / metabolism* MAP Kinase Signaling System / physiology* Mice Mitogen-Activated Protein Kinase 3 / genetics Mitogen-Activated Protein Kinase 3 / metabolism Phosphatidylinositol 3-Kinases / genetics Phosphatidylinositol 3-Kinases / metabolism Proto-Oncogene Proteins c-akt / genetics Proto-Oncogene Proteins c-akt / metabolism* p38 Mitogen-Activated Protein Kinases / genetics p38 Mitogen-Activated Protein Kinases / metabolism |
| IF | 4.238 |
| Times Cited | 35 |
| WOS Category | BIOCHEMISTRY & MOLECULAR BIOLOGY |
| Altmetric score |
オルトメトリクス指標項目
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| Total number of mentions | 0 |
| Altmetric score changes over past 6months | 0.0 |
| Resource | |
| Human and Animal Cells | ATDC5(RCB0565) |