Dexamethasone Enhances Osteogenic Differentiation of Bone Marrow- and Muscle-Derived Stromal Cells and Augments Ectopic Bone Formation Induced by Bone Morphogenetic Protein-2

Abstract

We evaluated whether dexamethasone augments the osteogenic capability of bone marrow-derived stromal cells (BMSCs) and muscle tissue-derived stromal cells (MuSCs), both of which are thought to contribute to ectopic bone formation induced by bone morphogenetic protein-2 (BMP-2), and determined the underlying mechanisms. Rat BMSCs and MuSCs were cultured in growth media with or without 10-7 M dexamethasone and then differentiated under osteogenic conditions with dexamethasone and BMP-2. The effects of dexamethasone on cell proliferation and osteogenic differentiation, and also on ectopic bone formation induced by BMP-2, were analyzed. Dexamethasone affected not only the proliferation rate but also the subpopulation composition of BMSCs and MuSCs, and subsequently augmented their osteogenic capacity during osteogenic differentiation. During osteogenic induction by BMP-2, dexamethasone also markedly affected cell proliferation in both BMSCs and MuSCs. In an in vivo ectopic bone formation model, bone formation in muscle-implanted scaffolds containing dexamethasone and BMP-2 was more than two fold higher than that in scaffolds containing BMP-2 alone. Our results suggest that dexamethasone potently enhances the osteogenic capability of BMP-2 and may thus decrease the quantity of BMP-2 required for clinical application, thereby reducing the complications caused by excessive doses of BMP-2. Highlights: 1. Dexamethasone induced selective proliferation of bone marrow- and muscle-derived cells with higher differentiation potential. 2. Dexamethasone enhanced the osteogenic capability of bone marrow- and muscle-derived cells by altering the subpopulation composition. 3. Dexamethasone augmented ectopic bone formation induced by bone morphogenetic protein-2.

Sulfated hyaluronic acid and dexamethasone possess a synergistic potential in the differentiation of osteoblasts from human bone marrow stromal cells

“…Thus, an upregulation of this signaling pathway after Dex exposition may confirm augmented BMP-2 signaling as suggested previously. 20 Nevertheless, we found a downregulation of EIF2 signaling after exposure to SH, which may be linked to the binding of BMP-2 to the sulfated GAG. 40 However, the combined usage of Dex and SH restored EIF2 signaling to basal levels.…”

“…13,18,19 Further, as it has been discussed, the direct effect of Dex on the cells is only minor but augments the effects of other signaling molecules, as was shown for BMP-2. 20 Proteomics studies aimed at elucidating Dex-triggered effects are rare and only include the murine osteoprogenitor cell line MC3T3-E1, trabecular meshwork cells, asthmatic mice lungs, and endometrial fluid. [21][22][23] A study on MC3T3-E1 cells elucidates the proteomic background in GIOP by administering high doses of Dex of 1 μM.…”

Distinct Gene Expression Patterns Defining Human Osteoblasts' Response to BMP2 Treatment: Is the Therapeutic Success All a Matter of Timing?

“…In the present model we wanted to investigate whether osteogenic differentiation can be improved by rhBMP2 treatment. However, several reports discussing the influence of dexamethasone on rhBMP treatment exist [24,25], ranging from augmentation to inhibition. The experimental conditions used in the present model are based on preliminary work from our group [18,19], which showed significant upregulation of rhBMP2 signaling by Smad1/5/8 phosphorylation and BRE reporter assay.…”

Rat Osteosarcoma Cells as a Therapeutic Target Model for Osteoregeneration via Sclerostin Knockdown

“…Effects of glucocorticoids on SOST expression [Moester et al, 2010] and bone formation [Pierotti et al, 2008], however, depend on the experimental conditions. Thus, in a recent study, Yuasa et al [2015] described improved bone formation in rats by loading TM staining in various differentiation media on day 7 after seeding and silencing with si-scl-1 and si-scl-3 relative to NC control. After 7 days in OM, DAPI-stained nuclei (in blue) show reduced cells per area in cultures treated with si-scl-1 and siscl-3 (upper row).…”