Effect of bone morphogenetic protein-2 (BMP-2) or troglitazone, as an inducer of osteogenic cells or adipocytes, on differentiation of a bone marrow mesenchymal progenitor cell line established from temperature-sensitive (ts) simian virus (SV) 40 T-antigen gene transgenic mice.
TBR31-2 is one of the bone marrow stromal cell lines. Differentiation toward osteogenic cells and calcification was observed when TBR31-2 cells were cultured for 4 weeks. Bone morphogenetic protein-2 (BMP-2) stimulated alkaline phosphatase (ALP) activity in a dose- and time-dependent manner. On the other hand, troglitazone increased oil droplet accumulation in a dose-dependent manner. In the presence of BMP-2, an increase of expression in osteogenic cell differentiation marker genes and a decrease of expression in adipocyte differentiation marker genes were observed with the exception of the induced expression of peroxisome proliferator-activated receptor gamma (PPARgamma), however, troglitazone, a ligand of PPARgamma treatment exhibited the opposite tendency. Interestingly, treatment with both BMP-2 and troglitazone resulted in a decrease of ALP activity and an increase of oil droplet accumulation. Reverse tanscription-polymerase chain reaction (RT-PCR) analysis also indicated that osteogenic differentiation markers decreased and that adipocyte differentiation markers increased. Thus, when the cells were cultured with BMP-2, osteogenic differentiation was enhanced while the expression of PPARgamma was maintained, and the addition of troglitazone caused a significant number of differentiated cells into adipocytes. These findings indicate that BMP-2 enhanced osteogenic differentiation and the expression of adipogenic transcription factor (PPARgamma) followed by osteogenic differentiation without activation of PPARgamma by its ligand.
Nishii
Naomi
N
First Department of Biochemistry, School of Pharmaceutical Sciences, Mukogawa Women's University, Nishinomiya, Hyogo 663-8179, Japan.
Arai
Michitsugu
M
Yanai
Nobuaki
N
Togari
Akifumi
A
Nakabayashi
Toshikatsu
T
D017667:Adipocytes / Q000187:drug effects / Q000502:physiology*; D000818:Animals; D000880:Anthraquinones / Q000378:metabolism; D029681:Arabidopsis Proteins / Q000235:genetics / Q000378:metabolism; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics / Q000378:metabolism; D001854:Bone Marrow Cells / Q000166:cytology / Q000187:drug effects; D055396:Bone Morphogenetic Protein 2 / Q000494:pharmacology*; D002454:Cell Differentiation / Q000187:drug effects*; D002461:Cell Line, Transformed; D002839:Chromans / Q000494:pharmacology*; D004187:Disaccharides / Q000235:genetics / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D059630:Mesenchymal Stem Cells / Q000187:drug effects*; D051379:Mice; D008822:Mice, Transgenic; D010012:Osteogenesis / Q000187:drug effects* / Q000502:physiology; D012333:RNA, Messenger / Q000378:metabolism; D017299:Rod Opsins / Q000235:genetics / Q000378:metabolism; D013539:Simian virus 40 / Q000235:genetics; D013696:Temperature; D045162:Thiazolidinediones / Q000494:pharmacology*; D013997:Time Factors; D000077288:Troglitazone
D000880:Anthraquinones; D029681:Arabidopsis Proteins; D051792:Basic Helix-Loop-Helix Proteins; D055396:Bone Morphogenetic Protein 2; D002839:Chromans; D004187:Disaccharides; D007004:Hypoglycemic Agents; D012333:RNA, Messenger; D017299:Rod Opsins; D045162:Thiazolidinediones; D000077288:Troglitazone; C512167:BDG protein, Arabidopsis; C525719:Bmp2 protein, mouse; C075668:Tcf3 protein, mouse; C095853:short-wavelength opsin; C064333:ruberythric acid