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Two-day-treatment of Activin-A leads to transient change in SV-HFO osteoblast gene expression and reduction in matrix mineralization.

ABSTRACT: Activins regulate bone formation by controlling osteoclasts and osteoblasts. We investigated Activin-A mechanism of action on human osteoblast mineralization, RNA and microRNA (miRNA) expression profile. A single 2-day treatment of Activin-A at Day 5 of osteoblast differentiation significantly reduced matrix mineralization. Activin A-treated osteoblasts responded with transient change in gene expression, in a 2-wave-fashion. The 38 genes differentially regulated during the first wave (within 8 hr after Activin A start) were involved in transcription regulation. In the second wave (1-2 days after Activin A start), 65 genes were differentially regulated and related to extracellular matrix. Differentially expressed genes in both waves were associated to transforming growth factor beta signaling. We identified which microRNAs modulating osteoblast differentiation were regulated by Activin-A. In summary, 2-day treatment with Activin-A in premineralization period of osteoblast cultures influenced miRNAs, gene transcription, and reduced matrix mineralization. Modulation of Activin A signaling might be useful to control bone quality for therapeutic purposes.

SUBMITTER: Baroncelli M

PROVIDER: S-EPMC7028110 | biostudies-literature | 2020 May

REPOSITORIES: biostudies-literature

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Two-day-treatment of Activin-A leads to transient change in SV-HFO osteoblast gene expression and reduction in matrix mineralization.

Baroncelli Marta M Drabek Ksenija K Eijken Marco M van der Eerden Bram C J BCJ van de Peppel Jeroen J van Leeuwen Johannes P T M JPTM

Journal of cellular physiology 20191030 5

Activins regulate bone formation by controlling osteoclasts and osteoblasts. We investigated Activin-A mechanism of action on human osteoblast mineralization, RNA and microRNA (miRNA) expression profile. A single 2-day treatment of Activin-A at Day 5 of osteoblast differentiation significantly reduced matrix mineralization. Activin A-treated osteoblasts responded with transient change in gene expression, in a 2-wave-fashion. The 38 genes differentially regulated during the first wave (within 8 h ...[more]

PMID: 31667867

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Project description:Bone loss occurs as a consequence of a variety of diseases as well as from traumatic injuries, and often requires therapeutic intervention. Strategies for repairing and replacing damaged and/or lost bone tissue include the use of biomaterials and medical implant devices with and without osteoinductive coatings. The soluble growth factor angiopoietin-1 (Ang-1) has been found to promote cell adhesion and survival in a range of cell types including cardiac myocytes, endothelial cells and fibroblasts through an integrin-dependent mechanism. Furthermore, the short sequence QHREDGS has been identified as the integrin-binding sequence of Ang-1 and as a synthetic peptide has been found to possess similar integrin-dependent effects as Ang-1 in the aforementioned cell types. Integrins have been implicated in osteoblast differentiation and bone mineralization, processes critical to bone regeneration. By binding integrins on the osteoblast surface, QHREDGS could promote cell survival and adhesion, as well as conceivably osteoblast differentiation and bone mineralization. Here we immobilized QHREDGS onto polyacrylate (PA)-coated titanium (Ti) plates and polyethylene glycol (PEG) hydrogels. The osteoblast differentiation marker, alkaline phosphatase, peaked in activity 4-12 days earlier on the QHREDGS-immobilized PA-coated Ti plates than on the unimmobilized, DGQESHR (scrambled)- and RGDS-immobilized surfaces. Significantly more bone matrix was deposited on the QHREDGS-immobilized Ti surface than on the other surfaces as determined by atomic force microscopy. The QHREDGS-immobilized hydrogels also had a significantly higher mineral-to-matrix (M/M) ratio determined by Fourier transform infrared spectroscopy. Alizarin Red S and von Kossa staining and quantification, and environmental scanning electron microscopy showed that while both the QHREDGS- and RGDS-immobilized surfaces had extensive mineralization relative to the unimmobilized and DGQESHR-immobilized surfaces, the mineralization was more considerable on the QHREDGS-immobilized surface, both with and without the induction of osteoblast differentiation. Finally, treatment of cell monolayers with soluble QHREDGS was demonstrated to upregulate osteogenic gene expression. Taken together, these results demonstrate that the QHREDGS peptide is osteoinductive, inducing osteoblast differentiation, bone matrix deposition and mineralization.

Dataset Information

Two-day-treatment of Activin-A leads to transient change in SV-HFO osteoblast gene expression and reduction in matrix mineralization.

Publications

Two-day-treatment of Activin-A leads to transient change in SV-HFO osteoblast gene expression and reduction in matrix mineralization.

Similar Datasets

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