Expression and function of Dlx genes in the osteoblast lineage
| Autor: | Stephen E. Harris, Mina Mina, Inga Marijanović, Haitao Li, William B. Upholt, Mary Louise Stover, Ivo Kalajzic, Jelica Gluhak Heinrich, Ivana Erceg, Alexander C. Lichtler, Mark S. Kronenberg, Dimitrios Velonis |
|---|---|
| Rok vydání: | 2008 |
| Předmět: |
musculoskeletal diseases
Cellular differentiation FACS Osteoblast lineage Bone Marrow Cells Mice Inbred Strains Mice Transgenic Biology GFP Osteocytes Polymerase Chain Reaction Article Mice 03 medical and health sciences 0302 clinical medicine Gene expression medicine Animals Dlx2 RNA Messenger Northern blot Cloning Molecular Dlx5 Bone Dlx6 Molecular Biology Dlx3 030304 developmental biology Homeodomain Proteins Regulation of gene expression 0303 health sciences Osteoblasts Osteoblast differentiation Cell Differentiation Osteoblast Cell Biology DLX5 Molecular biology medicine.anatomical_structure Animals Newborn Gene Expression Regulation 030220 oncology & carcinogenesis Osteocyte embryonic structures Knockout mouse Stromal Cells Transcription Factors Developmental Biology |
| Zdroj: | Developmental Biology. 316:458-470 |
| ISSN: | 0012-1606 |
| DOI: | 10.1016/j.ydbio.2008.01.001 |
| Popis: | Our laboratory and others have shown that overexpression of Dlx5 stimulates osteoblast differentiation. Dlx5−/−/Dlx6−/− mice have more severe craniofacial and limb defects than Dlx5−/−, some of which are potentially due to defects in osteoblast maturation. We wished to investigate the degree to which other Dlx genes compensate for the lack of Dlx5, thus allowing normal development of the majority of skeletal elements in Dlx5−/− mice. Dlx gene expression in cells from different stages of the osteoblast lineage isolated by FACS sorting showed that Dlx2, Dlx5 and Dlx6 are expressed most strongly in less mature osteoblasts, whereas Dlx3 is very highly expressed in differentiated osteoblasts and osteocytes. In situ hybridization and Northern blot analysis demonstrated the presence of endogenous Dlx3 mRNA within osteoblasts and osteocytes. Dlx3 strongly upregulates osteoblastic markers with a potency comparable to Dlx5. Cloned chick or mouse Dlx6 showed stimulatory effects on osteoblast differentiation. Our results suggest that Dlx2 and Dlx6 have the potential to stimulate osteoblastic differentiation and may compensate for the absence of Dlx5 to produce relatively normal osteoblastic differentiation in Dlx5 knockout mice, while Dlx3 may play a distinct role in late stage osteoblast differentiation and osteocyte function. |
| Databáze: | OpenAIRE |
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