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Publication : NO-β-catenin crosstalk modulates primitive streak formation prior to embryonic stem cell osteogenic differentiation.

First Author  Ding H Year  2012
Journal  J Cell Sci Volume  125
Issue  Pt 22 Pages  5564-77
PubMed ID  22946055 Mgi Jnum  J:200282
Mgi Id  MGI:5507962 Doi  10.1242/jcs.081703
Citation  Ding H, et al. (2012) NO-beta-catenin crosstalk modulates primitive streak formation prior to embryonic stem cell osteogenic differentiation. J Cell Sci 125(Pt 22):5564-77
abstractText  Nitric oxide (NO) has been shown to play a crucial role in bone formation in vivo. We sought to determine the temporal effect of NO on murine embryonic stem cells (ESCs) under culture conditions that promote osteogenesis. Expression profiles of NO pathway members and osteoblast-specific markers were analyzed using appropriate assays. We found that NO was supportive of osteogenesis specifically during an early phase of in vitro development (days 3-5). Furthermore, ESCs stably overexpressing the inducible NO synthase showed accelerated and enhanced osteogenesis in vitro and in bone explant cultures. To determine the role of NO in early lineage commitment, a stage in ESC differentiation equivalent to primitive streak formation in vivo, ESCs were transfected with a T-brachyury-GFP reporter. Expression levels of T-brachyury and one of its upstream regulators, beta-catenin, the major effector in the canonical Wnt pathway, were responsive to NO levels in differentiating primitive streak-like cells. Our results indicate that NO may be involved in early differentiation through regulation of beta-catenin and T-brachyury, controlling the specification of primitive-streak-like cells, which may continue through differentiation to later become osteoblasts.
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