Transcriptomic characterization of signaling pathways associated with osteoblastic differentiation of MC-3T3E1 cells
| Autor: | Moahad Dar, Louis M. Luttrell, Hesham M. El-Shewy, Diane Gesty-Palmer, Jeremy L. Barth, Katherine M. Robinson, Courtney J. Haycraft |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Cell signaling Microarrays Cellular differentiation Gene Expression Datasets as Topic Signal transduction Extracellular matrix Mice 0302 clinical medicine Animal Cells Bone Density Osteogenesis Medicine and Health Sciences Gene Regulatory Networks Connective Tissue Cells Oligonucleotide Array Sequence Analysis Regulation of gene expression 0303 health sciences Multidisciplinary Wnt signaling pathway Signaling cascades Cell Differentiation Osteoblast 3T3 Cells Osteoblast Differentiation Extracellular Matrix Cell biology Autocrine Communication Bioassays and Physiological Analysis medicine.anatomical_structure RANKL Connective Tissue 030220 oncology & carcinogenesis Medicine Bone Remodeling Cellular Types Anatomy Network Analysis Research Article musculoskeletal diseases Computer and Information Sciences Science 030209 endocrinology & metabolism Biology Research and Analysis Methods 03 medical and health sciences Paracrine signalling Paracrine Communication Genetics medicine Animals Gene Regulation Autocrine signalling 030304 developmental biology Osteoblasts Gene Expression Profiling Mesenchymal stem cell Biology and Life Sciences Signaling Networks Gene expression profiling Biological Tissue 030104 developmental biology TGF-beta signaling cascade biology.protein Transcriptome Developmental Biology |
| Zdroj: | PLoS ONE, Vol 14, Iss 1, p e0204197 (2019) PLoS ONE |
| ISSN: | 1932-6203 |
| Popis: | Bone remodeling involves the coordinated actions of osteoclasts, which resorb the calcified bony matrix, and osteoblasts, which refill erosion pits created by osteoclasts to restore skeletal integrity and adapt to changes in mechanical load. Osteoblasts are derived from pluripotent mesenchymal stem cell precursors, which undergo differentiation under the influence of a host of local and environmental cues. To characterize the autocrine/paracrine signaling networks associated with osteoblast maturation and function, we performed gene network analysis using complementary “agnostic” DNA microarray and “targeted” NanoString™ nCounter datasets derived from murine MC3T3-E1 cells induced to undergo synchronized osteoblastic differentiation in vitro. Pairwise datasets representing changes in gene expression associated with growth arrest (day 2 to 5 in culture), differentiation (day 5 to 10 in culture), and osteoblast maturation (day 10 to 28 in culture) were analyzed using Ingenuity Systems™ Pathways Analysis to generate predictions about signaling pathway activity based on the temporal sequence of changes in target gene expression. Our data indicate that some pathways known to be involved in osteoblast differentiation, e.g. Wnt/β-catenin signaling, are most active early in the process, while others, e.g. TGFβ/BMP, cytokine/JAK-STAT and TNFα/RANKL signaling, increase in activity as differentiation progresses. Collectively, these pathways contribute to the sequential expression of genes involved in the synthesis and mineralization of extracellular matrix. These results provide insight into the temporal coordination and complex interplay between signaling networks controlling gene expression during osteoblast differentiation. A more complete understanding of these processes may aid the discovery of novel methods to promote osteoblast development for the trea™ent of conditions characterized by low bone mineral density. |
| Databáze: | OpenAIRE |
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