title: Effects of continuous dexamethasone treatment on differentiation capabilities of bone marrow-derived mesenchymal cells.
abstract: Human bone marrow-derived mesenchymal cells (hBMMCs) originate from cell populations in the bone marrow and are capable of differentiating along multiple mesenchymal lineages. To differentiate hBMMCs into osteoblasts, adipocytes and chondrocytes, dexamethasone has been used as a differentiation reagent. We hypothesized that dexamethasone would augment the responsiveness of BMMCs to other differentiation reagents and not define the lineage. This study investigated the effect of continuous treatment with 100 nM dexamethasone on the differentiation of BMMCs into three different lineages. hBMMCs cultured with continuous dexamethasone treatment (100 nM) exhibited higher mRNA expression levels of osteogenic markers and higher positive rates of colony forming unit assays for osteogenesis compared to hBMMCs treated with dexamethasone only during the differentiation culture. Furthermore, continuous dexamethasone treatment augmented bone formation capability of monkey-derived BMMCs in a bone induction experimental model at an extra skeletal site. In addition, continuously dexamethasone-treated hBMMCs formed larger chondrogenic pellets and expressed SOX9 at higher level than the control BMMCs. Likewise, continuous dexamethasone treatment facilitated adipogenic differentiation based on mRNA level and colony forming unit analysis. To investigate the mechanism of the augmentation of differentiation, further studies on apoptosis were conducted. The studies indicated that dexamethasone selectively induced apoptosis of some populations of hBMMCs which were thought to have poor differentiation capability.
authors: Oral and Maxillofacial Surgery, Graduate School, Tokyo Medical and Dental University, Tokyo, Japan.
authors: Hidekazu
authors: H
authors: Oshina
authors: Shinichi
authors: S
authors: Sotome
authors: Toshitaka
authors: T
authors: Yoshii
authors: Ichiro
authors: I
authors: Torigoe
authors: Yumi
authors: Y
authors: Sugata
authors: Hidetsugu
authors: H
authors: Maehara
authors: Eriko
authors: E
authors: Marukawa
authors: Ken
authors: K
authors: Omura
authors: Kenichi
authors: K
authors: Shinomiya
mesh_terms: D050156:Adipogenesis / Q000187:drug effects; D000469:Alkaline Phosphatase / Q000378:metabolism; D000818:Animals; D015415:Biomarkers; D001854:Bone Marrow Cells / Q000166:cytology* / Q000187:drug effects* / Q000378:metabolism; D053148:Caspase 3 / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects*; D002478:Cells, Cultured; D019902:Chondrocytes / Q000166:cytology / Q000187:drug effects; D003114:Colony-Forming Units Assay; D003592:Cytophotometry; D003907:Dexamethasone / Q000494:pharmacology*; D005260:Female; D006801:Humans; D008251:Macaca; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000187:drug effects* / Q000378:metabolism; D010006:Osteoblasts / Q000187:drug effects / Q000378:metabolism; D010012:Osteogenesis / Q000187:drug effects
chemical_list: D015415:Biomarkers; D003907:Dexamethasone; D000469:Alkaline Phosphatase; D053148:Caspase 3