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| Status |
Public on Oct 15, 2010 |
| Title |
DLK1 Is a Novel Regulator of Bone Mass That Mediates Estrogen-Deficiency Induced Bone Loss in Mice |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by array
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| Summary |
DLK1/FA-1 (delta-like 1/fetal antigen-1) is a transmembrane protein belonging to Notch/Delta family that acts as a membrane-associated or a soluble protein to regulate regeneration of a number of adult tissues. Here, we examined the role of DLK1/FA-1 in bone biology using osteoblast-specific-Dlk1 over-expressing mice (Col1-Dlk1). Col1-Dlk1 mice displayed growth retardation and significantly reduced total body weight and bone mineral density (BMD). μCT-scanning revealed a reduced trabecular and cortical bone volume fraction. Tissue-level histomorphometric analysis demonstrated decreased bone formation rate and enhanced bone resorption in Col1-Dlk1 as compared to WT. At a cellular level, DLK1 markedly reduced the total number of bone marrow (BM)-derived CFU-F, as well as their osteogenic capacity. In a number of in vitro culture systems, DLK1 stimulated osteoclastogenesis indirectly through osteoblast-dependent increased production of pro-inflammatory bone resorbing cytokines (e.g, Il7, Tnfa and Ccl3). We found that ovariectomy (ovx)-induced bone loss was associated with increased production of DLK1 in bone marrow by activated T-cells. However, Dlk1-/- mice were protected from ovx-induced bone loss. Thus, we identified DLK1 as a novel regulator of bone mass that function to inhibit bone formation and to stimulate bone resorption. Increasing DLK1 production by T-cells under estrogen deficiency suggests its possible use as a therapeutic target for preventing postmenopausal bone loss.
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| Overall design |
Calvarial osteoblasts were grown from neonatal mice overexpressing Dlk1 and their non-transgenic littermate controls. Three separate cultures from each of the two genotypes were combined and analysed by Affymetrix microarray MOE430 2.0.
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| Contributor(s) |
Abdallah BM, Ditzel N, Mahmood A, Isa A, Traustadottir GA, Schilling AF, Ruiz-Hidalgo M, Laborda J, Amling M, Kassem M |
| Citation(s) |
21308776 |
| Submission date |
Jun 03, 2010 |
| Last update date |
Jan 08, 2019 |
| Contact name |
Basem Abdallah |
| E-mail(s) |
babdallah@health.sdu.dk
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| Organization name |
Odense University Hospital
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| Department |
Dept. of Endocrinology
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| Lab |
KMEB
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| Street address |
J.B. Winslows Vej 25
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| City |
Odense C |
| ZIP/Postal code |
5000 |
| Country |
Denmark |
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| Platforms (1) |
| GPL339 |
[MOE430A] Affymetrix Mouse Expression 430A Array |
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| Samples (2) |
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| Relations |
| BioProject |
PRJNA128987 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE22113_RAW.tar |
4.4 Mb |
(http)(custom) |
TAR (of CEL, CHP) |
| Processed data included within Sample table |
| Processed data provided as supplementary file |
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