Stimulation of chondrogenesis in ATDC5 chondroprogenitor cells and hypertrophy in mouse by Genkwadaphnin

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Title
Stimulation of chondrogenesis in ATDC5 chondroprogenitor cells and hypertrophy in mouse by Genkwadaphnin
Author(s)
H J Choi; M Nepal; Y R Park; Hyeong Kyu Lee; Sei Ryang Oh; Y Soh
Bibliographic Citation
European Journal of Pharmacology, vol. 655, no. 1, pp. 9-15
Publication Year
2011
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.
Keyword
ATDC5 chondroprogenitor cellChondrogenesisGenkwadaphninHypertrophy
ISSN
0014-2999
Publisher
Elsevier
DOI
http://dx.doi.org/10.1016/j.ejphar.2011.01.012
Type
Article
Appears in Collections:
Ochang Branch Institute > 1. Journal Articles
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