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A crucial role of caspase-3 in osteogenic differentiation of bone marrow stromal stem cells

Cited 181 time in Web of Science Cited 0 time in Scopus
Authors
Miura, Masako; Chen, Xiao-Dong; Allen, Matthew R.; Bi, Yanming; Gronthos, Stan; Seo, Byoung-Moo; Lakhani, Saquib; Flavell, Richard A.; Feng, Xin-Hua; Robey, Pamela Gehron; Young, Marian; Shi, Songtao
Issue Date
2004-12
Publisher
American Society for Clinical Investigation
Citation
J Clin Invest. 114(12):1704-1713
Abstract
Caspase-3 is a critical enzyme for apoptosis and cell survival. Here we report delayed ossification and decreased bone mineral density in caspase-3-deficient (Casp3(-/-) and Casp3(+/-)) mice due to an attenuated osteogenic differentiation of bone marrow stromal stem cells (BMSSCs). The mechanism involved in the impaired differentiation of BMSSCs is due, at least partially, to the overactivated TGF-beta/Smad2 signaling pathway and the upregulated expressions of p53 and p21 along with the downregulated expressions of Cdk2 and Cdc2, and ultimately increased replicative senescence. In addition, the overactivated TGF-beta/Smad2 signaling may result in the compromised Runx2/Cbfa1 expression in preosteoblasts. Furthermore, we demonstrate that caspase-3 inhibitor, a potential agent for clinical treatment of human diseases, caused accelerated bone loss in ovariectomized mice, which is also associated with the overactivated TGF-beta/Smad2 signaling in BMSSCs. This study demonstrates that caspase-3 is crucial for the differentiation of BMSSCs by influencing TGF-beta/Smad2 pathway and cell cycle progression
ISSN
0021-9738
Language
English
URI
https://hdl.handle.net/10371/68810
DOI
https://doi.org/10.1172/JCI200420427
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College of Dentistry/School of Dentistry (치과대학/치의학대학원)Dept. of Dentistry (치의학과)Journal Papers (저널논문_치의학과)
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