Stimulation of osteogenic differentiation and inhibition of adipogenic differentiation in bone marrow stromal cells by alendronate via ERK and JNK activation.
To elucidate the mechanism of the effect of bisphosphonates on bone metabolism, we investigated the effect of alendronate, a widely used bisphosphonate, on osteogenic and adipogenic differentiation in bone marrow stromal cells (BMSCs) derived from ovariectomized SD rats. Alendronate treatment not only increased the mRNA level of bone morphogenetic protein-2, runt-related transcription factor 2, osteopontin, bone sialoprotein, and alkaline phosphatase activity after osteogenic induction, but also decreased the mRNA level of peroxisome proliferator activated receptor gamma 2 and total droplet number indicated by Oil Red O staining after adipogenic induction. The effect of alendronate treatment was dose-dependent, and the difference of the osteogenic or the adipogenic potential between the treated group and the non-treated group was statistically significant (p<0.001). The MAPK-specific inhibitors, PD98059 and SP600125, but not the p38-specific inhibitor, blocked the alendronate-induced regulation of BMSC differentiation. Analysis of BMSCs induced in the presence of alendronate revealed an immediate increase in ERK and JNK phosphorylation. Taken together, these data suggest that alendronate acts on BMSCs to stimulate osteogenic differentiation and inhibit adipogenic differentiation in a dose-dependent manner; this effect is mediated via activating ERK and JNK.
Fu
Lingjie
L
Department of Orthopaedic Surgery, Ninth People's Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, PR China; Orthopaedic Cellular and Molecular Biology Laboratory, Institute of Health Sciences, Chinese Academy of Sciences, and Shanghai Jiaotong University School of Medicine, Shanghai, PR China. Electronic address: lingjiefu@sohu.com.
Tang
Tingting
T
Department of Orthopaedic Surgery, Ninth People's Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, PR China. Electronic address: tingtingtang@hotmail.com.
Miao
Yanying
Y
Orthopaedic Cellular and Molecular Biology Laboratory, Institute of Health Sciences, Chinese Academy of Sciences, and Shanghai Jiaotong University School of Medicine, Shanghai, PR China. Electronic address: yymiaomed@sina.com.
Zhang
Shuhong
S
Department of Orthopaedic Surgery, Ninth People's Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, PR China. Electronic address: shuhongzh1980@yahoo.com.cn.
Qu
Zhihu
Z
Orthopaedic Cellular and Molecular Biology Laboratory, Institute of Health Sciences, Chinese Academy of Sciences, and Shanghai Jiaotong University School of Medicine, Shanghai, PR China. Electronic address: zhqu@sibs.ac.cn.
Dai
Kerong
K
Department of Orthopaedic Surgery, Ninth People's Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, PR China; Orthopaedic Cellular and Molecular Biology Laboratory, Institute of Health Sciences, Chinese Academy of Sciences, and Shanghai Jiaotong University School of Medicine, Shanghai, PR China. Electronic address: krdai@sibs.ac.cn.
D050156:Adipogenesis / Q000187:drug effects*; D019386:Alendronate / Q000494:pharmacology*; D000818:Animals; D001483:Base Sequence; D015153:Blotting, Western; D001854:Bone Marrow Cells / Q000166:cytology* / Q000187:drug effects; D001842:Bone and Bones / Q000166:cytology*; D019070:Cell Lineage; D002478:Cells, Cultured; D017931:DNA Primers; D004789:Enzyme Activation; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D048670:MAP Kinase Kinase 4 / Q000378:metabolism*; D010012:Osteogenesis / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017154:Stromal Cells / Q000166:cytology
D017931:DNA Primers; D048049:Extracellular Signal-Regulated MAP Kinases; D048670:MAP Kinase Kinase 4; D019386:Alendronate