title: Ethanol extract of Lithospermum erythrorhizon Sieb. et Zucc. promotes osteoblastogenesis through the regulation of Runx2 and Osterix.
abstract: Bone remodeling and homeostasis are largely the result of the coordinated action of osteoblasts and osteoclasts. Osteoblasts are responsible for bone formation. The differentiation of osteoblasts is regulated by the transcription factors, Runx2 and Osterix. Natural products of plant origin are still a major part of traditional medicinal systems in Korea. The root of Lithospermum erythrorhizon Sieb. et Zucc. (LR), the purple gromwell, is an herbal medicine used for inflammatory and infectious diseases. LR is an anti-inflammatory and exerts anticancer effects by inducing the apoptosis of cancer cells. However, the precise molecular signaling mechanisms of osteoblastogenesis as regards LR and osteoblast transcription are not yet known. In this study, we investigated the effects of ethanol (EtOH) extract of LR (LES) on the osteoblast differentiation of C2C12 myoblasts induced by bone morphogenetic protein 4 (BMP4) and the potential involvement of Runx2 and Osterix in these effects. We found that the LES exhibited an ability to induce osteoblast differentiation. LES increased the expression of the osteoblast marker, alkaline phosphatase (ALP), as well as its activity, as shown by ALP staining and ALP activity assay. LES also increased mineralization, as shown by Alizarin Red S staining. Treatment with LES increased the protein levels (as shown by immunoblotting), as well as the transcriptional activity of Runx2 and Osterix and enhanced osteogenic activity. These results suggest that LES modulates osteoblast differentiation at least in part through Runx2 and Osterix.
authors.affiliation: College of Pharmacy, Chonnam National University, Gwangju 500-757, Republic of Korea.
authors.forename: You Hee
authors.initials: YH
authors.lastname: Choi
authors.affiliation: Department of Herbal Crop Research, National Institute of Horticultural and Herbal Science, RDA, Eumseong 369-873, Republic of Korea.
authors.forename: Geum Soog
authors.initials: GS
authors.lastname: Kim
authors.affiliation: College of Pharmacy, Chungnam National University, Daejeon 305-764, Republic of Korea.
authors.forename: Jae Ho
authors.initials: JH
authors.lastname: Choi
authors.affiliation: College of Pharmacy, Chungnam National University, Daejeon 305-764, Republic of Korea.
authors.forename: Sun Woo
authors.initials: SW
authors.lastname: Jin
authors.affiliation: College of Pharmacy, Chungnam National University, Daejeon 305-764, Republic of Korea.
authors.forename: Hyung Gyun
authors.initials: HG
authors.lastname: Kim
authors.affiliation: College of Pharmacy, Chonnam National University, Gwangju 500-757, Republic of Korea.
authors.forename: Younho
authors.initials: Y
authors.lastname: Han
authors.affiliation: Department of Herbal Crop Research, National Institute of Horticultural and Herbal Science, RDA, Eumseong 369-873, Republic of Korea.
authors.forename: Dae Young
authors.initials: DY
authors.lastname: Lee
authors.affiliation: YD Global Life Science Co., Ltd., Seongnam 462-807, Republic of Korea.
authors.forename: Soo Im
authors.initials: SI
authors.lastname: Choi
authors.affiliation: Department of Herbal Crop Research, National Institute of Horticultural and Herbal Science, RDA, Eumseong 369-873, Republic of Korea.
authors.forename: Seung Yu
authors.initials: SY
authors.lastname: Kim
authors.affiliation: Department of Herbal Crop Research, National Institute of Horticultural and Herbal Science, RDA, Eumseong 369-873, Republic of Korea.
authors.forename: Young Sup
authors.initials: YS
authors.lastname: Ahn
authors.affiliation: College of Pharmacy, Chonnam National University, Gwangju 500-757, Republic of Korea.
authors.forename: Kwang Youl
authors.initials: KY
authors.lastname: Lee
authors.affiliation: College of Pharmacy, Chungnam National University, Daejeon 305-764, Republic of Korea.
authors.forename: Hye Gwang
authors.initials: HG
authors.lastname: Jeong
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D055415:Bone Morphogenetic Protein 4 / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects / Q000235:genetics; D050659:Core Binding Factor Alpha 1 Subunit / Q000235:genetics* / Q000378:metabolism; D000431:Ethanol / Q000737:chemistry*; D005786:Gene Expression Regulation / Q000187:drug effects*; D057809:HEK293 Cells; D006801:Humans; D029684:Lithospermum / Q000737:chemistry*; D051379:Mice; D010006:Osteoblasts / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D010012:Osteogenesis / Q000187:drug effects* / Q000235:genetics; D010936:Plant Extracts / Q000494:pharmacology*; D000076182:Sp7 Transcription Factor; D014157:Transcription Factors / Q000235:genetics*; D014158:Transcription, Genetic / Q000187:drug effects
chemical_list: D015415:Biomarkers; D055415:Bone Morphogenetic Protein 4; D050659:Core Binding Factor Alpha 1 Subunit; D010936:Plant Extracts; D000076182:Sp7 Transcription Factor; C479466:Sp7 protein, mouse; D014157:Transcription Factors; D000431:Ethanol