Bergapten promotes bone marrow stromal cell differentiation into osteoblasts in vitro and in vivo

• Published in: Molecular and cellular biochemistry 2015-11, Vol.409 (1-2), p.113-122
• Main Authors: Xiao, Ji-jie, Zhao, Wen-ji, Zhang, Xin-tao, Zhao, Wen-long, Wang, Xiao-xia, Yin, Shu-hui, Jiang, Fang, Zhao, Yin-xia, Chen, Fang-ni, Li, Shao-lin
• Format: Article
• Language: English
• Subjects: Alkaline Phosphatase - biosynthesis; Analysis; Animals; beta Catenin - metabolism; Biochemistry; Biomedical and Life Sciences; Bone marrow; Bone Marrow Cells - cytology; Bone mineral density; Bones; Cardiology; Cell differentiation; Cell Differentiation - drug effects; Cells, Cultured; Cellular biology; Collagen Type I - biosynthesis; Core Binding Factor Alpha 1 Subunit - biosynthesis; Density; Female; Immunohistochemistry; Life Sciences; Medical Biochemistry; Mesenchymal Stromal Cells - cytology; Methoxsalen - analogs & derivatives; Methoxsalen - pharmacology; Mice; Mice, Inbred C57BL; Oncology; Osteoblasts - cytology; Osteocalcin - biosynthesis; Osteogenesis - drug effects; Osteoporosis; Osteoporosis - pathology; Photosensitizing Agents - pharmacology; Postmenopausal women; Sp7 Transcription Factor; Transcription Factors - biosynthesis; Wnt Proteins - metabolism; Wnt Signaling Pathway - drug effects
• ISSN: 0300-8177; 1573-4919
• DOI: 10.1007/s11010-015-2517-9

Many recent studies have suggested that bergapten (BP), a class of native compound with numerous biological activities such as anti-resorptive properties, may exert protective effects against postmenopausal bone loss. However, it remains unknown whether BP regulates or improves the osteogenic function of bone marrow stromal cells (BMSCs) in the treatment and prevention of osteoporosis. In our study, BMSCs were cultured in osteogenic induction medium with the addition of BP for 2 weeks and an ovariectomized mouse model of osteoporosis was used to investigate the anti-resorptive effect of BP by gavage administration for 3 months. The concentrations of BP used were 0.1, 1, and 10 μmol/L in vitro and the gavage dose was 20 mg/kg/d. The result of our study indicated that BP promotes the expression of alkaline phosphatase (ALP) by BMSCs in vitro in a dose-dependent manner, as revealed by ALP staining. Runt-related transcription factor 2 and osteocalcin were up-regulated both in vitro and vivo, while osterix and collagen Iα1, assessed by immunofluorescence and immunohistochemistry, were correspondingly raised in the presence of BP in BMSCs in vitro. In addition, a protective effect of BP against ovariectomy-induced bone loss was found by distal femur micro-CT scanning, with improvements of bone metabolism parameters such as bone mineral density, trabecular number, and trabecular separation. Furthermore, WNT/β-catenin signaling was activated in the presence of BP in BMSCs in osteogenic culture. Finally, BP promoted differentiation of BMSCs into osteoblasts by up-regulation of the WNT/β-catenin pathway. Graphical abstract