title: Decursin inhibits osteoclastogenesis by downregulating NFATc1 and blocking fusion of pre-osteoclasts.
abstract: Bone sustains its structure through dynamic interaction between osteoblastic cells and osteoclastic cells. But imbalance may lead to osteoporosis caused by overactivated osteoclast cells that have bone-resorbing function. Recently, herbs have been researched as major sources of medicines in many countries. In vitro and in vivo anti-osteoclastogenic activity of Angelica gigas NAKAI have been reported, but the biological activity of decursin, its major component in osteoclast differentiation is still unknown. Therefore, in this study, we explored whether decursin could affect RANKL-mediated osteoclastogenesis. The results showed that decursin efficiently inhibited RANKL-activated osteoclast differentiation by inhibiting transcriptional and translational expression of NFATc1, a major factor in RANKL-mediated osteoclastogenesis. Furthermore, decursin decreased fusion and migration of pre-osteoclasts by downregulating mRNA expression levels of DC-STAMP and β3 integrin, respectively. In addition, decursin prevents lipopolysaccharide (LPS)-induced bone erosion in vivo. In summary, decursin could prevent osteoclastogenesis and inflammatory bone loss via blockage of NFATc1 activity and fusion and migration of pre-osteoclasts, and it could be developed as a potent phytochemical candidate for treating pathologies of bone diseases.
authors.affiliation: Department of Pharmacy, Sunchon National University, Suncheon 540-742, Republic of Korea.
authors.forename: Kwang-Jin
authors.initials: KJ
authors.lastname: Kim
authors.affiliation: Research Institute of Basic Science, Sunchon National University, Suncheon 540-742, Republic of Korea.
authors.forename: Jeong-Tae
authors.initials: JT
authors.lastname: Yeon
authors.affiliation: Laboratory of Translational Therapeutics, Pharmacology Research Center, Division of Drug Discovery Research, Korea Research Institute of Chemical Technology, Daejeon 305-600, Republic of Korea.
authors.forename: Sik-Won
authors.initials: SW
authors.lastname: Choi
authors.affiliation: Laboratory of Translational Therapeutics, Pharmacology Research Center, Division of Drug Discovery Research, Korea Research Institute of Chemical Technology, Daejeon 305-600, Republic of Korea; Department of Biology, Chungnam National University, Daejeon 305-510, Republic of Korea.
authors.forename: Seong-Hee
authors.initials: SH
authors.lastname: Moon
authors.affiliation: Laboratory of Translational Therapeutics, Pharmacology Research Center, Division of Drug Discovery Research, Korea Research Institute of Chemical Technology, Daejeon 305-600, Republic of Korea.
authors.forename: Byung Jun
authors.initials: BJ
authors.lastname: Ryu
authors.affiliation: College of Veterinary Medicine, Kyungpook National University, Daegu 702-701, Republic of Korea.
authors.forename: Ri
authors.initials: R
authors.lastname: Yu
authors.affiliation: College of Veterinary Medicine, Kyungpook National University, Daegu 702-701, Republic of Korea.
authors.forename: Sang-Joon
authors.initials: SJ
authors.lastname: Park
authors.affiliation: Laboratory of Translational Therapeutics, Pharmacology Research Center, Division of Drug Discovery Research, Korea Research Institute of Chemical Technology, Daejeon 305-600, Republic of Korea. Electronic address: hwan@krict.re.kr.
authors.forename: Seong Hwan
authors.initials: SH
authors.lastname: Kim
authors.affiliation: Department of Pharmacy, Sunchon National University, Suncheon 540-742, Republic of Korea. Electronic address: sony@sunchon.ac.kr.
authors.forename: Young-Jin
authors.initials: YJ
authors.lastname: Son
mesh_terms: D000818:Animals; D001578:Benzopyrans / Q000378:metabolism* / Q000494:pharmacology; D002087:Butyrates / Q000378:metabolism* / Q000494:pharmacology; D002459:Cell Fusion; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation / Q000187:drug effects / Q000502:physiology*; D051379:Mice; D008813:Mice, Inbred ICR; D050778:NFATC Transcription Factors / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D010010:Osteoclasts / Q000378:metabolism*; D010012:Osteogenesis / Q000187:drug effects / Q000502:physiology*
chemical_list: D001578:Benzopyrans; D002087:Butyrates; D050778:NFATC Transcription Factors; C494005:Nfatc1 protein, mouse; C101278:decursin