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PLoS One. 2019 Jan 4;14(1):e0204197. doi: 10.1371/journal.pone.0204197. eCollection 2019.

Transcriptomic characterization of signaling pathways associated with osteoblastic differentiation of MC-3T3E1 cells.

Author information

1
Department of Medicine, Medical University of South Carolina, Charleston, South Carolina, United States of America.
2
Department of Biochemistry & Molecular Biology, Medical University of South Carolina, Charleston, South Carolina, United States of America.
3
Ralph H. Johnson Veterans Affairs Medical Center, Charleston, South Carolina, United States of America.
4
Department of Medicine, Duke University Medical Center, Durham, North Carolina, United States of America.
5
Department of Biology, Mississippi College, Clinton, Mississippi, United States of America.
6
Department of Regenerative Medicine and Cell Biology, Medical University of South Carolina, Charleston, South Carolina, United States of America.

Abstract

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 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 treatment of conditions characterized by low bone mineral density.

Conflict of interest statement

The authors have declared that no competing interests exist.

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