Dexamethasone enhances osteogenic differentiation of bone marrow- and muscle-derived stromal cells and augments ectopic bone formation induced by bone morphogenetic protein-2

Masato Yuasa; Tsuyoshi Yamada; Takashi Taniyama; Tomokazu Masaoka; Wei Xuetao; Toshitaka Yoshii; Masaki Horie; Hiroaki Yasuda; Toshimasa Uemura; Atsushi Okawa; Shinichi Sotome

doi:10.1371/journal.pone.0116462

Dexamethasone enhances osteogenic differentiation of bone marrow- and muscle-derived stromal cells and augments ectopic bone formation induced by bone morphogenetic protein-2

PLoS One. 2015 Feb 6;10(2):e0116462. doi: 10.1371/journal.pone.0116462. eCollection 2015.

Authors

Affiliations

¹ Department of Orthopaedic and Spinal Surgery, Graduate School, Tokyo Medical and Dental University, Tokyo, Japan; Global Center of Excellence (GCOE) Program, International Research Center for Molecular Science in Tooth and Bone Diseases, Tokyo Medical and Dental University, Tokyo, Japan.
² Department of Orthopaedic and Spinal Surgery, Graduate School, Tokyo Medical and Dental University, Tokyo, Japan.
³ Hyperbaric Medical Center, University Hospital of Medicine, Tokyo Medical and Dental University, Tokyo, Japan.
⁴ National Institute of Advanced Industrial Science and Technology, Ibaraki, Japan.
⁵ Department of Orthopaedic and Spinal Surgery, Graduate School, Tokyo Medical and Dental University, Tokyo, Japan; Department of Orthopaedic Research and Development, Graduate School, Tokyo Medical and Dental University, Tokyo, Japan.

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Bone Marrow Cells / cytology
Bone Marrow Cells / metabolism*
Bone Morphogenetic Protein 2 / metabolism*
Cell Differentiation / drug effects*
Dexamethasone / pharmacology*
Male
Muscle Cells / cytology
Muscle Cells / metabolism*
Osteogenesis / drug effects*
Rats
Rats, Inbred F344
Stromal Cells / cytology
Stromal Cells / metabolism

Substances

Bmp2 protein, rat
Bone Morphogenetic Protein 2
Dexamethasone

Grants and funding

This study was partially supported by grants from the Japanese Ministry of Health, Labor and Welfare and by Olympus Corporation. The funders had no role in study design, data collection and analysis, decision to publish or preparation of the manuscript.