title: Ginsenoside Re Promotes Osteoblast Differentiation in Mouse Osteoblast Precursor MC3T3-E1 Cells and a Zebrafish Model.
abstract: Bone homeostasis is tightly regulated to balance bone formation and bone resorption. Many anabolic drugs are used as bone-targeted therapeutic agents for the promotion of osteoblast-mediated bone formation or inhibition of osteoclast-mediated bone resorption. Previous studies showed that ginsenoside Re has the effect of the suppression of osteoclast differentiation in mouse bone-marrow derived macrophages and zebrafish. Herein, we investigated whether ginsenoside Re affects osteoblast differentiation and mineralization in in vitro and in vivo models. Mouse osteoblast precursor MC3T3-E1 cells were used to investigate cell viability, alkaline phosphatase (ALP) activity, and mineralization. In addition, we examined osteoblastic signaling pathways. Ginsenoside Re affected ALP activity without cytotoxicity, and we also observed the stimulation of osteoblast differentiation through the activation of osteoblast markers including runt-related transcription factor 2, type 1 collagen, ALP, and osteocalcin in MC3T3-E1 cells. Moreover, Alizarin red S staining indicated that ginsenoside Re increased osteoblast mineralization in MC3T3-E1 cells and zebrafish scales compared to controls. These results suggest that ginsenoside Re promotes osteoblast differentiation as well as inhibits osteoclast differentiation, and it could be a potential therapeutic agent for bone diseases.
authors.affiliation: Anticancer Agent Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Cheongju 28116, Korea. hyemin88@kribb.re.kr.|World Class Institute, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Cheongju 28116, Korea. hyemin88@kribb.re.kr.|Department of Biomolecular Science, University of Science and Technology, Daejeon 34113, Korea. hyemin88@kribb.re.kr.
authors.forename: Hye-Min
authors.initials: HM
authors.lastname: Kim
authors.affiliation: Anticancer Agent Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Cheongju 28116, Korea. waikiki@kribb.re.kr.|World Class Institute, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Cheongju 28116, Korea. waikiki@kribb.re.kr.|Department of Biomolecular Science, University of Science and Technology, Daejeon 34113, Korea. waikiki@kribb.re.kr.
authors.forename: Dong Hyun
authors.initials: DH
authors.lastname: Kim
authors.affiliation: Anticancer Agent Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Cheongju 28116, Korea. hjhan@kribb.re.kr.|World Class Institute, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Cheongju 28116, Korea. hjhan@kribb.re.kr.|Department of Biomolecular Science, University of Science and Technology, Daejeon 34113, Korea. hjhan@kribb.re.kr.
authors.forename: Ho-Jin
authors.initials: HJ
authors.lastname: Han
authors.affiliation: World Class Institute, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Cheongju 28116, Korea. springcm@kribb.re.kr.
authors.forename: Chan-Mi
authors.initials: CM
authors.lastname: Park
authors.affiliation: Anticancer Agent Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Cheongju 28116, Korea. raogs@kribb.re.kr.|World Class Institute, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Cheongju 28116, Korea. raogs@kribb.re.kr.
authors.forename: Srinivas Rao
authors.initials: SR
authors.lastname: Ganipisetti
authors.affiliation: Department of Botany and Microbiology, Addiriyah Chair for Environmental Studies, College of Science, King Saud University, P.O. Box 2455, Riyadh 11451, Saudi Arabia. mvalanarasu@gmail.com.
authors.forename: Mariadhas
authors.initials: M
authors.lastname: Valan Arasu
authors.affiliation: Department of Medicinal Crop Research Institute, National Institute of Horticultural & Herbal Science, Rural Development Administration, Eumseong 27709, Korea. kyo9128@korea.kr.
authors.forename: Young Ock
authors.initials: YO
authors.lastname: Kim
authors.affiliation: Department of Medicinal Crop Research Institute, National Institute of Horticultural & Herbal Science, Rural Development Administration, Eumseong 27709, Korea. pcg@korea.kr.
authors.forename: Chun Geun
authors.initials: CG
authors.lastname: Park
authors.affiliation: Anticancer Agent Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Cheongju 28116, Korea. bykim@kribb.re.kr.|World Class Institute, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Cheongju 28116, Korea. bykim@kribb.re.kr.|Department of Biomolecular Science, University of Science and Technology, Daejeon 34113, Korea. bykim@kribb.re.kr.
authors.forename: Bo-Yeon
authors.initials: BY
authors.lastname: Kim
authors.affiliation: Anticancer Agent Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Cheongju 28116, Korea. soungnak@kribb.re.kr.|World Class Institute, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Cheongju 28116, Korea. soungnak@kribb.re.kr.|Department of Biomolecular Science, University of Science and Technology, Daejeon 34113, Korea. soungnak@kribb.re.kr.
authors.forename: Nak-Kyun
authors.initials: NK
authors.lastname: Soung
mesh_terms: D016475:3T3 Cells; D000469:Alkaline Phosphatase / Q000378:metabolism; D000818:Animals; D001862:Bone Resorption / Q000188:drug therapy*; D002454:Cell Differentiation / Q000187:drug effects*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D024042:Collagen Type I / Q000378:metabolism; D050659:Core Binding Factor Alpha 1 Subunit / Q000378:metabolism; D004789:Enzyme Activation / Q000187:drug effects; D036145:Ginsenosides / Q000494:pharmacology*; D051379:Mice; D010006:Osteoblasts / Q000166:cytology*; D015675:Osteocalcin / Q000378:metabolism; D010012:Osteogenesis / Q000187:drug effects*; D005894:Panax / Q000737:chemistry; D015398:Signal Transduction / Q000187:drug effects; D015027:Zebrafish
chemical_list: D024042:Collagen Type I; D050659:Core Binding Factor Alpha 1 Subunit; D036145:Ginsenosides; D015675:Osteocalcin; C049864:ginsenoside Re; D000469:Alkaline Phosphatase
keywords: Ginsenoside Re; bone; osteoblast differentiation