Silibinin promotes osteoblast differentiation of human bone marrow stromal cells via bone morphogenetic protein signaling.
Silibinin is the major active constituent of the natural compound silymarin; several studies suggest that silibinin possesses antihepatotoxic properties and anticancer effects against carcinoma cells. However, no study has yet investigated the effect of silibinin on osteogenic differentiation of human bone marrow stem cells (hBMSCs). The aim of this study was to evaluate the effect of silibinin on osteogenic differentiation of hBMSCs. In this study, the hBMSCs were cultured in an osteogenic medium with 0, 1, 10 or 20 μmol/l silibinin respectively. hBMSCs viability was analyzed by cell number quantification assay and cells osteogenic differentiation was evaluated by alkaline phosphatas (ALP) activity assay, Von Kossa staining and real time-polymerase chain reaction (RT-PCR). We found that silibinin promoted ALP activity in hBMSCs without affecting their proliferation. The mineralization of hBMSCs was enhanced by treatment with silibinin. Silibinin also increased the mRNA expressions of Collagen type I (COL-I), ALP, Osteocalcin (OCN), Osterix, bone morphogenetic protein-2 (BMP-2) and Runt-related transcription factor 2 (RUNX2). The BMP antagonist noggin and its receptor kinase inhibitors dorsomorphin and LDN-193189 attenuated silibinin-promoted ALP activity. Furthermore, BMP-responsive and Runx2-responsive reporters were activated by silibinin treatment. These results indicate that silibinin enhances osteoblast differentiation probably by inducing the expressions of BMPs and activating BMP and RUNX2 pathways. Thus, silibinin may play an important therapeutic role in osteoporosis patients by improving osteogenic differentiation of BMSCs.
Department of Orthopedic Surgery, The Second Affiliated Hospital of Wenzhou Medical College, 109 Xue Yuan xi Road, Wenzhou 325000, China. Electronic address: yingxiaozhou@sina.com.
Xiaozhou
X
Ying
Liaojun
L
Sun
Xiaowei
X
Chen
Huazi
H
Xu
Xiaoshan
X
Guo
Hua
H
Chen
Jianjun
J
Hong
Shaowen
S
Cheng
Lei
L
Peng
D000328:Adult; D000469:Alkaline Phosphatase / Q000378:metabolism; D019485:Bone Morphogenetic Proteins / Q000378:metabolism*; D002113:Calcification, Physiologic / Q000187:drug effects; D002118:Calcium / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects*; D050659:Core Binding Factor Alpha 1 Subunit / Q000235:genetics; D005260:Female; D006801:Humans; D008297:Male; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000187:drug effects*; D008875:Middle Aged; D010006:Osteoblasts / Q000166:cytology*; D015398:Signal Transduction / Q000187:drug effects*; D000077385:Silybin; D012838:Silymarin / Q000494:pharmacology*; D000076182:Sp7 Transcription Factor; D014157:Transcription Factors / Q000235:genetics; D015854:Up-Regulation / Q000187:drug effects
D019485:Bone Morphogenetic Proteins; D050659:Core Binding Factor Alpha 1 Subunit; D012838:Silymarin; D000076182:Sp7 Transcription Factor; C478163:SP7 protein, human; D014157:Transcription Factors; D000077385:Silybin; D000469:Alkaline Phosphatase; D002118:Calcium
Bone morphogenetic protein; Human bone marrow stromal cells (hBMSCs); Osteogenic; RUNX2; Silibinin