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- W2027889543 abstract "Activin belongs to the transforming growth factor-β (TGF-β) family of growth and differentiation factors, and is implicated in the regulation of cell growth and differentiation in a variety of biological systems. Activins are expressed in many tissues, including bone tissue, where they regulate bone formation by controlling both osteoblasts and osteoclast functions. We have shown previously that activin A treatment of human pre-osteoblast cultures decreases matrix mineralization and alkaline phosphatase activity (ALP) in these cultures. The aim of the current project is to unravel the molecular networks underlying these activin actions in a systems biology manner. By performing different timing and duration treatments, we show that only a single activin A treatment at day 5 of culture, is sufficient to reduce matrix mineralization measured at the end of culture after 19 days. Treatment with activin A during later stages of osteoblast differentiation was ineffective. Contrary to activin, similar treatments using an inhibitor of activin signaling, results in stimulation of matrix mineralization. At the signal transduction level, activins stimulate Smad2/3 phosphorylation. We investigated Smad phosphorylation dynamics in activin A-treated osteoblasts by Western Blotting and Phospho Flow Cytometry, where we show that one hour after activin A stimulation Smad2 phosphorylation reaches its maximum. These insights into activin A and Smad phosphorylation dynamics demonstrates the importance of timing of treatment and that only a short term pulse of activation can modulate cell fate up to at least 7-14 days later. This knowledge is of great value for understanding control of osteoblast differentiation and bone formation as well as from a therapeutic point of view. Disclosure of Interest: None declared" @default.
- W2027889543 created "2016-06-24" @default.
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- W2027889543 date "2010-06-01" @default.
- W2027889543 modified "2023-10-05" @default.
- W2027889543 title "The transient receptor potential channel TRPV6 is dynamically expressed in osteoblasts and linked to mineralisation" @default.
- W2027889543 doi "https://doi.org/10.1016/j.bone.2010.04.260" @default.
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