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.
Highlights
Bone grafting is widely used in orthopedic surgery, for the treatment of spinal fusion, complicated fractures, and defects created by tumor resection, all of which require massive bone grafts
The proliferation rates of the bone marrow-derived stromal cells (BMSCs) treated with 10-7 and 10-6 M dexamethasone were lower than those of untreated cells at the early stage of culture
These results indicate that dexamethasone strongly suppresses the proliferation of BMSCs and muscle tissue-derived stromal cells (MuSCs), MuSCs
Summary
Bone grafting is widely used in orthopedic surgery, for the treatment of spinal fusion, complicated fractures, and defects created by tumor resection, all of which require massive bone grafts. Autologous bone grafting is the gold standard for restoration of bone defects because of its superior osteogenic capability, as it provides a source of regenerative cells, an osteoconductive scaffold, and a void filler that biomechanically supports the surrounding bone structure, in contrast to other materials such as allografts and synthetic materials. Harvesting of autologous bone grafts from patients may cause donor site morbidities such as infection, deep hematoma formation, sensory loss, cosmetic disability, and continuous pain [1,2,3]. Many recent studies have focused on developing engineering methods that combine mesenchymal stromal cells (MSCs) with materials to achieve osteogenic induction in vivo. These techniques remain unsatisfactory and require improvement
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