RRC ID 18190
著者 Choi HJ, Nepal M, Park YR, Lee HK, Oh SR, Soh Y.
タイトル Stimulation of chondrogenesis in ATDC5 chondroprogenitor cells and hypertrophy in mouse by Genkwadaphnin.
ジャーナル Eur J Pharmacol
Abstract The growth in height of the bone plate is a result of endochondral proliferation in epiphyseal growth plates and the conversion of chondrocytes into new bone. The control of chondrogenic differentiation and hypertrophy is critical for these processes. The present study was aimed to demonstrate the chondromodulating activity of Genkwadaphnin. ATDC5 cultures treated with Genkwadaphnin produced cartilaginous nodules that were greater in number and larger in size than control cultures. Genkwadaphnin treated ATDC5 cells also stained more intensely with Alcian blue than control cells, suggesting greater synthesis of matrix proteoglycans in the former. Genkwadaphnin markedly induced the activation of alkaline phosphatase, as well as the expression of chondrogenic marker genes such as type II collagen, aggrecan, type I collagen, type X collagen, osteocalcin, and bone sialoprotein in ATDC5 cells. The expression of signaling molecules involved in chondrogenesis including Smad4, Sox9, and β-catenin was also induced by treatment of ATDC5 cells with Genkwadaphnin. Furthermore, Genkwadaphnin induced the activation of extracellular signal-regulated kinase (ERK) and c-Jun N-terminal kinase (JNK). To analyze the role of Genkwadaphnin in growth plate chondrocyte in vivo, we analyzed chondrogenesis in mice treated with Genkwadaphnin. The significant expansion in growth plate and hypertrophic zone and numerous numbers of chondrocyte positive cells in hypertrophic and proliferative bone areas were observed. These observations provide the first evidence that Genkwadaphnin has chondromodulating activity and may open new therapeutic avenues to treat a variety of skeletal diseases, such as dwarfism.
巻・号 655(1-3)
ページ 9-15
公開日 2011-3-25
DOI 10.1016/j.ejphar.2011.01.012
PII S0014-2999(11)00052-5
PMID 21266170
MeSH Alkaline Phosphatase / metabolism Animals Biomarkers / metabolism Bone Diseases / drug therapy Cartilage / drug effects Cartilage / growth & development Cell Differentiation / drug effects Cell Line Chondrogenesis / drug effects* Chondrogenesis / genetics Diterpenes / pharmacology* Diterpenes / therapeutic use Extracellular Signal-Regulated MAP Kinases / metabolism Gene Expression Regulation / drug effects Growth Plate / cytology Growth Plate / drug effects Hypertrophy / physiopathology JNK Mitogen-Activated Protein Kinases / metabolism Male Mice Proteoglycans / metabolism Stem Cells / cytology* Stem Cells / enzymology Stem Cells / metabolism* Tibia / cytology Tibia / drug effects Tibia / growth & development
IF 3.263
引用数 9
WOS 分野 PHARMACOLOGY & PHARMACY
リソース情報
ヒト・動物細胞 ATDC5(RCB0565)