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Bone Abstracts (2016) 5 P158 | DOI: 10.1530/boneabs.5.P158

ECTS2016 Poster Presentations Cell biology: osteoblasts and bone formation (36 abstracts)

A single 2-day pulse of activin-A leads to a transient change in gene expression eventually followed by reduction in extracellular matrix mineralization

Marta Baroncelli , Ksenija Drabek , Marco Eijken , Jeroen van de Peppel & Johannes van Leeuwen


Erasmus Medical Center, Rotterdam, The Netherlands.

Activins belong to the transforming growth factor-β superfamily, and they regulate bone formation by controlling both osteoclast and osteoblast behaviour. We have previously shown that activin-A strongly inhibited matrix mineralization in osteoblast cultures, and that activin A-signalling was most effective before the onset of mineralization.

The aim of this study was therefore to investigate how an early activin-A pulse affected osteoblast mineralization and gene expression profile, to unravel the molecular mechanisms of activin-A signalling.

Human osteoblasts (svHFOs) were treated with a 2-day-pulse of activin-A, and mineralization and gene expression profiling have been analysed up to 10 days later.

Our results showed that a single pulse of activin-A at day 5 of culture was sufficient to significantly reduce matrix mineralization at later stages of osteoblast differentiation (P<0.001). Activin treatment led to a transient peak (1 h) in SMAD3 phosphorylation, as assessed by Phospho Flow Cytometry. A single pulse of activin-A is therefore responsible for changes at later stages of cell differentiation. Gene expression profiling showed that the activin A-pulse induced a transient change in osteoblast gene expression, in a 2-phase fashion over time: first phase (1–8 h after activin A-pulse), second phase (1–2 days). During the first phase, 38 genes were differentially regulated (P<0.01). These changes were mainly related to transcription regulation and some of these transcription factors contained SMAD-responsive elements. In the second phase, 65 genes were differentially regulated (P<0.01), and they were mainly involved in ECM and cell-matrix adhesion.

In summary, these findings give new insights into the mechanism by which activin-A modulates osteoblast differentiation, by influencing gene transcription and leading then to alterations of matrix mineralization. Modulation of activin A-signalling might be useful for therapeutic purposes to control bone formation and mineralization and thereby quality.

Volume 5

43rd Annual European Calcified Tissue Society Congress

Rome, Italy
14 May 2016 - 17 May 2016

European Calcified Tissue Society 

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