title: Effects of Tanshinone IIA on osteogenic differentiation of mouse bone marrow mesenchymal stem cells.
abstract: Tanshinone IIA (TSA) is a lipophilic diterpene purified from the Chinese herb Danshen, which exhibits potent antioxidant and anti-inflammatory properties. Effect of TSA remains largely uninvestigated on the osteogenic differentiation of bone marrow mesenchymal stem cells (BM-MSCs), which are widely used in cell-based therapy of bone diseases. In the present study, both ALP activity at day 7 and calcium content at day 24 were upregulated during the osteogenesis of mouse BM-MSCs treated with TSA (1 and 5 μM), demonstrating that it promoted the osteogenesis at both early and late stages. We found that TSA promoted osteogenesis and inhibited osteoclastogenesis, evident by RT-PCR analysis of osteogenic marker gene expressions. However, osteogenesis was inhibited by TSA at 20 μM. We further revealed that TSA (1 and 5 μM) upregulated BMP and Wnt signaling. Co-treatment with Wnt inhibitor DKK-1 or BMP inhibitor noggin significantly decreased the TSA-promoted osteogenesis, indicating that upregulation of BMP and Wnt signaling plays a significant role and contributes to the TSA-promoted osteogenesis. Of clinical interest, our study suggests TSA as a promising therapeutic strategy during implantation of BM-MSCs for a more effective treatment of bone diseases.
authors.affiliation: Department of Orthopaedic Surgery, Nanjing Medical University Affiliated Wuxi Second Hospital, 68 Zhongshan Road, Wuxi, 214001, China.
authors.forename: Kejun
authors.initials: K
authors.lastname: Qian
authors.affiliation: Department of Orthopaedic Surgery, Nanjing Medical University Affiliated Wuxi Second Hospital, 68 Zhongshan Road, Wuxi, 214001, China.
authors.forename: Huazhong
authors.initials: H
authors.lastname: Xu
authors.affiliation: Department of Orthopaedic Surgery, Nanjing Medical University Affiliated Wuxi Second Hospital, 68 Zhongshan Road, Wuxi, 214001, China.
authors.forename: Teng
authors.initials: T
authors.lastname: Dai
authors.affiliation: Department of Orthopaedic Surgery, Nanjing Medical University Affiliated Wuxi Second Hospital, 68 Zhongshan Road, Wuxi, 214001, China. kqshi23@163.com.
authors.forename: Keqing
authors.initials: K
authors.lastname: Shi
mesh_terms: D045784:Abietanes / Q000494:pharmacology*; D000469:Alkaline Phosphatase / Q000378:metabolism; D000818:Animals; D019485:Bone Morphogenetic Proteins / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D005786:Gene Expression Regulation / Q000187:drug effects; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000187:drug effects*; D008807:Mice, Inbred BALB C; D010006:Osteoblasts / Q000166:cytology / Q000187:drug effects*; D010012:Osteogenesis / Q000187:drug effects* / Q000235:genetics / Q000502:physiology; D060449:Wnt Signaling Pathway / Q000187:drug effects
chemical_list: D045784:Abietanes; D019485:Bone Morphogenetic Proteins; C021751:tanshinone; D000469:Alkaline Phosphatase; D002118:Calcium
keywords: Bone disease; Mesenchymal stem cells; Osteoclastogenesis; Osteogenesis; Tanshinone IIA