title: Bergapten promotes bone marrow stromal cell differentiation into osteoblasts in vitro and in vivo.
abstract: 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.
authors.affiliation: Department of Medical Image, The Third Affiliated Hospital of Southern Medical University, 183 West Zhongshan Avenue, 510630, Guangzhou, China.|Academy of Orthopedics, Guangdong Province, Guangzhou, 510630, Guangdong, China.
authors.forename: Ji-jie
authors.initials: JJ
authors.lastname: Xiao
authors.affiliation: Department of Medical Image, Inner Mongolia Bayannaoer City Hospital, Bayannaoer City, 015000, China.|Department of Medical Image, Inner Mongolia People's Hospital, Hohhot, 010017, China.
authors.forename: Wen-ji
authors.initials: WJ
authors.lastname: Zhao
authors.affiliation: Department of Medical Image, The Third Affiliated Hospital of Southern Medical University, 183 West Zhongshan Avenue, 510630, Guangzhou, China.|Academy of Orthopedics, Guangdong Province, Guangzhou, 510630, Guangdong, China.
authors.forename: Xin-tao
authors.initials: XT
authors.lastname: Zhang
authors.affiliation: Clinical Laboratory, Inner Mongolia Bayannaoer City Hospital, Bayannaoer City, 015000, China.
authors.forename: Wen-long
authors.initials: WL
authors.lastname: Zhao
authors.affiliation: Endocrinology Department, Inner Mongolia Bayannaoer City Hospital, Bayannaoer City, 015000, China.
authors.forename: Xiao-xia
authors.initials: XX
authors.lastname: Wang
authors.affiliation: Clinical Laboratory, Inner Mongolia Bayannaoer City Hospital, Bayannaoer City, 015000, China.
authors.forename: Shu-hui
authors.initials: SH
authors.lastname: Yin
authors.affiliation: Department of Medical Image, The Third Affiliated Hospital of Southern Medical University, 183 West Zhongshan Avenue, 510630, Guangzhou, China.|Academy of Orthopedics, Guangdong Province, Guangzhou, 510630, Guangdong, China.
authors.forename: Fang
authors.initials: F
authors.lastname: Jiang
authors.affiliation: Department of Medical Image, The Third Affiliated Hospital of Southern Medical University, 183 West Zhongshan Avenue, 510630, Guangzhou, China.|Academy of Orthopedics, Guangdong Province, Guangzhou, 510630, Guangdong, China.
authors.forename: Yin-xia
authors.initials: YX
authors.lastname: Zhao
authors.affiliation: Department of Medical Image, The Third Affiliated Hospital of Southern Medical University, 183 West Zhongshan Avenue, 510630, Guangzhou, China.|Academy of Orthopedics, Guangdong Province, Guangzhou, 510630, Guangdong, China.
authors.forename: Fang-ni
authors.initials: FN
authors.lastname: Chen
authors.affiliation: Department of Medical Image, The Third Affiliated Hospital of Southern Medical University, 183 West Zhongshan Avenue, 510630, Guangzhou, China. lishaolin1963@163.com.|Academy of Orthopedics, Guangdong Province, Guangzhou, 510630, Guangdong, China. lishaolin1963@163.com.
authors.forename: Shao-lin
authors.initials: SL
authors.lastname: Li
mesh_terms: D000078223:5-Methoxypsoralen; D000469:Alkaline Phosphatase / Q000096:biosynthesis; D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D024042:Collagen Type I / Q000096:biosynthesis; D050659:Core Binding Factor Alpha 1 Subunit / Q000096:biosynthesis; D005260:Female; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D008730:Methoxsalen / Q000031:analogs & derivatives* / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D010006:Osteoblasts / Q000166:cytology*; D015675:Osteocalcin / Q000096:biosynthesis; D010012:Osteogenesis / Q000187:drug effects*; D010024:Osteoporosis / Q000473:pathology; D017319:Photosensitizing Agents / Q000494:pharmacology*; D000076182:Sp7 Transcription Factor; D014157:Transcription Factors / Q000096:biosynthesis; D051153:Wnt Proteins / Q000378:metabolism; D060449:Wnt Signaling Pathway / Q000187:drug effects*; D051176:beta Catenin / Q000378:metabolism
chemical_list: D024042:Collagen Type I; D050659:Core Binding Factor Alpha 1 Subunit; D017319:Photosensitizing Agents; C493716:Runx2 protein, mouse; D000076182:Sp7 Transcription Factor; C479466:Sp7 protein, mouse; D014157:Transcription Factors; D051153:Wnt Proteins; D051176:beta Catenin; D015675:Osteocalcin; D000078223:5-Methoxypsoralen; D000469:Alkaline Phosphatase; D008730:Methoxsalen
keywords: BMSC; Bergapten; Bone formation; Osteoblast; Osteoporosis