Interplay of Nkx3.2, Sox9 and Pax3 regulates chondrogenic differentiation of muscle progenitor cells
| Autor: | James P. Canner, David G. Little, Dana M. Cairns, Manpreet Sen, Li Zeng, Aaron Schindeler, Renjing Liu |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2012 |
| Předmět: |
Anatomy and Physiology
Cellular differentiation Bone Morphogenetic Protein 2 Muscle Proteins lcsh:Medicine Chick Embryo Signal transduction Muscle Development Biochemistry Fractures Bone Mice Molecular cell biology Transforming Growth Factor beta Myocyte Paired Box Transcription Factors Signaling in Cellular Processes lcsh:Science Musculoskeletal System Cells Cultured Fracture Healing 0303 health sciences Multidisciplinary Myogenesis Stem Cells 030302 biochemistry & molecular biology Signaling cascades Cell Differentiation SOX9 Transcription Factor Muscle Biochemistry Cell biology Extracellular Matrix Adult Stem Cells embryonic structures Cytochemistry Muscle Stem cell Cellular Types Chondrogenesis Immunocytochemistry Research Article medicine.medical_specialty Histology Satellite Cells Skeletal Muscle Cell fate determination Biology 03 medical and health sciences Internal medicine DNA-binding proteins medicine Animals Progenitor cell Bone PAX3 Transcription Factor 030304 developmental biology Homeodomain Proteins Muscle Cells lcsh:R Proteins Extracellular Matrix Composition Satellite virus Endocrinology Cartilage TGF-beta signaling cascade lcsh:Q Transcriptional Signaling Chickens Transcription Factors Developmental Biology |
| Zdroj: | PLoS ONE, Vol 7, Iss 7, p e39642 (2012) PLoS ONE |
| ISSN: | 1932-6203 |
| Popis: | Muscle satellite cells make up a stem cell population that is capable of differentiating into myocytes and contributing to muscle regeneration upon injury. In this work we investigate the mechanism by which these muscle progenitor cells adopt an alternative cell fate, the cartilage fate. We show that chick muscle satellite cells that normally would undergo myogenesis can be converted to express cartilage matrix proteins in vitro when cultured in chondrogenic medium containing TGFs3 or BMP2. In the meantime, the myogenic program is repressed, suggesting that muscle satellite cells have undergone chondrogenic differentiation. Furthermore, ectopic expression of the myogenic factor Pax3 prevents chondrogenesis in these cells, while chondrogenic factors Nkx3.2 and Sox9 act downstream of TGFs or BMP2 to promote this cell fate transition. We found that Nkx3.2 and Sox9 repress the activity of the Pax3 promoter and that Nkx3.2 acts as a transcriptional repressor in this process. Importantly, a reverse function mutant of Nkx3.2 blocks the ability of Sox9 to both inhibit myogenesis and induce chondrogenesis, suggesting that Nkx3.2 is required for Sox9 to promote chondrogenic differentiation in satellite cells. Finally, we found that in an in vivo mouse model of fracture healing where muscle progenitor cells were lineage-traced, Nkx3.2 and Sox9 are significantly upregulated while Pax3 is significantly downregulated in the muscle progenitor cells that give rise to chondrocytes during fracture repair. Thus our in vitro and in vivo analyses suggest that the balance of Pax3, Nkx3.2 and Sox9 may act as a molecular switch during the chondrogenic differentiation of muscle progenitor cells, which may be important for fracture healing. |
| Databáze: | OpenAIRE |
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